US20090304824A1 - Rapid-Melt Compositions, Methods of Making Same and Methods of Using Same - Google Patents
Rapid-Melt Compositions, Methods of Making Same and Methods of Using Same Download PDFInfo
- Publication number
- US20090304824A1 US20090304824A1 US12/409,574 US40957409A US2009304824A1 US 20090304824 A1 US20090304824 A1 US 20090304824A1 US 40957409 A US40957409 A US 40957409A US 2009304824 A1 US2009304824 A1 US 2009304824A1
- Authority
- US
- United States
- Prior art keywords
- composition
- rapid
- melt
- compositions
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 299
- 238000000034 method Methods 0.000 title abstract description 39
- 239000011230 binding agent Substances 0.000 claims description 52
- 239000000463 material Substances 0.000 claims description 49
- 239000003795 chemical substances by application Substances 0.000 claims description 40
- 239000003995 emulsifying agent Substances 0.000 claims description 32
- 239000000796 flavoring agent Substances 0.000 claims description 28
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 23
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 23
- 229930195725 Mannitol Natural products 0.000 claims description 22
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 22
- 239000000594 mannitol Substances 0.000 claims description 22
- 235000010355 mannitol Nutrition 0.000 claims description 22
- 239000000314 lubricant Substances 0.000 claims description 19
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 17
- 235000010755 mineral Nutrition 0.000 claims description 17
- 239000011707 mineral Substances 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 17
- 239000003085 diluting agent Substances 0.000 claims description 16
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 12
- 235000003599 food sweetener Nutrition 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 12
- 239000003765 sweetening agent Substances 0.000 claims description 12
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 11
- 229930003268 Vitamin C Natural products 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 11
- 235000019154 vitamin C Nutrition 0.000 claims description 11
- 239000011718 vitamin C Substances 0.000 claims description 11
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 8
- 229920000053 polysorbate 80 Polymers 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 7
- 229940068968 polysorbate 80 Drugs 0.000 claims description 7
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical group [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 4
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical group [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000004246 zinc acetate Substances 0.000 claims description 4
- 239000011670 zinc gluconate Substances 0.000 claims description 4
- 229960000306 zinc gluconate Drugs 0.000 claims description 4
- 235000011478 zinc gluconate Nutrition 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 235000014134 echinacea Nutrition 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000008117 stearic acid Chemical class 0.000 claims description 2
- 241000258180 Echinacea <Echinodermata> Species 0.000 claims 2
- 235000013355 food flavoring agent Nutrition 0.000 claims 1
- 239000011149 active material Substances 0.000 abstract description 38
- 238000007906 compression Methods 0.000 abstract description 23
- 230000006835 compression Effects 0.000 abstract description 23
- 238000010438 heat treatment Methods 0.000 abstract description 20
- 241000124008 Mammalia Species 0.000 abstract description 18
- 230000001225 therapeutic effect Effects 0.000 abstract description 17
- 230000000069 prophylactic effect Effects 0.000 abstract description 7
- 238000000465 moulding Methods 0.000 abstract description 4
- 239000000047 product Substances 0.000 description 93
- 239000003826 tablet Substances 0.000 description 50
- 239000003814 drug Substances 0.000 description 41
- 239000004480 active ingredient Substances 0.000 description 33
- 229940079593 drug Drugs 0.000 description 30
- 239000003925 fat Substances 0.000 description 27
- 235000019197 fats Nutrition 0.000 description 27
- 235000019634 flavors Nutrition 0.000 description 27
- 239000008187 granular material Substances 0.000 description 27
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 26
- 238000002156 mixing Methods 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 22
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 19
- 230000008569 process Effects 0.000 description 19
- 239000007788 liquid Substances 0.000 description 18
- -1 polyols and sugars Chemical compound 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 150000002632 lipids Chemical class 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000004615 ingredient Substances 0.000 description 14
- 239000002245 particle Substances 0.000 description 14
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 11
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 11
- 239000007767 bonding agent Substances 0.000 description 11
- 229960002442 glucosamine Drugs 0.000 description 11
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 10
- 229910000019 calcium carbonate Inorganic materials 0.000 description 10
- 235000010216 calcium carbonate Nutrition 0.000 description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 10
- 229960005489 paracetamol Drugs 0.000 description 10
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 9
- 230000001055 chewing effect Effects 0.000 description 9
- 229960000673 dextrose monohydrate Drugs 0.000 description 9
- 239000008108 microcrystalline cellulose Substances 0.000 description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 229940088594 vitamin Drugs 0.000 description 9
- 229930003231 vitamin Natural products 0.000 description 9
- 239000011782 vitamin Substances 0.000 description 9
- 239000001993 wax Substances 0.000 description 9
- 229940069428 antacid Drugs 0.000 description 8
- 239000003159 antacid agent Substances 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 235000013343 vitamin Nutrition 0.000 description 8
- 208000019695 Migraine disease Diseases 0.000 description 7
- 230000001458 anti-acid effect Effects 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 235000019629 palatability Nutrition 0.000 description 7
- 238000007873 sieving Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 235000012239 silicon dioxide Nutrition 0.000 description 7
- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 239000004376 Sucralose Substances 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 239000007910 chewable tablet Substances 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 239000008121 dextrose Substances 0.000 description 6
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 6
- 229960001031 glucose Drugs 0.000 description 6
- 201000008482 osteoarthritis Diseases 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 235000019408 sucralose Nutrition 0.000 description 6
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 6
- 235000019640 taste Nutrition 0.000 description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 5
- 239000005913 Maltodextrin Substances 0.000 description 5
- 229920002774 Maltodextrin Polymers 0.000 description 5
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 244000299461 Theobroma cacao Species 0.000 description 5
- 229960001138 acetylsalicylic acid Drugs 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 5
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 5
- 235000019219 chocolate Nutrition 0.000 description 5
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 5
- 238000005461 lubrication Methods 0.000 description 5
- 229940035034 maltodextrin Drugs 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229960001802 phenylephrine Drugs 0.000 description 5
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 5
- 230000000506 psychotropic effect Effects 0.000 description 5
- 210000003296 saliva Anatomy 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000000811 xylitol Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 4
- 229920002567 Chondroitin Polymers 0.000 description 4
- 235000005979 Citrus limon Nutrition 0.000 description 4
- 244000131522 Citrus pyriformis Species 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 4
- 239000004141 Sodium laurylsulphate Substances 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 4
- 229940035676 analgesics Drugs 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 230000001142 anti-diarrhea Effects 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 229940049706 benzodiazepine Drugs 0.000 description 4
- 150000001557 benzodiazepines Chemical class 0.000 description 4
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 4
- 235000020971 citrus fruits Nutrition 0.000 description 4
- 235000009508 confectionery Nutrition 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- 239000006186 oral dosage form Substances 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 229940001470 psychoactive drug Drugs 0.000 description 4
- 239000004089 psychotropic agent Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 150000005846 sugar alcohols Chemical class 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 235000010447 xylitol Nutrition 0.000 description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 4
- 229960002675 xylitol Drugs 0.000 description 4
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 3
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 241000167854 Bourreria succulenta Species 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229920001287 Chondroitin sulfate Polymers 0.000 description 3
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 206010017533 Fungal infection Diseases 0.000 description 3
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000031888 Mycoses Diseases 0.000 description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 206010039424 Salivary hypersecretion Diseases 0.000 description 3
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 240000006909 Tilia x europaea Species 0.000 description 3
- 235000011941 Tilia x europaea Nutrition 0.000 description 3
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 3
- 229930003270 Vitamin B Natural products 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 230000001773 anti-convulsant effect Effects 0.000 description 3
- 229940125681 anticonvulsant agent Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000003139 buffering effect Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 235000019693 cherries Nutrition 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 229940059329 chondroitin sulfate Drugs 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 235000013399 edible fruits Nutrition 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 229940075507 glyceryl monostearate Drugs 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 229960002146 guaifenesin Drugs 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000004571 lime Substances 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 229960002009 naproxen Drugs 0.000 description 3
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 208000026451 salivation Diseases 0.000 description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229940083542 sodium Drugs 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000001587 sorbitan monostearate Substances 0.000 description 3
- 235000011076 sorbitan monostearate Nutrition 0.000 description 3
- 229940035048 sorbitan monostearate Drugs 0.000 description 3
- 235000013599 spices Nutrition 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 229960002051 trandolapril Drugs 0.000 description 3
- 229960001722 verapamil Drugs 0.000 description 3
- 235000019156 vitamin B Nutrition 0.000 description 3
- 239000011720 vitamin B Substances 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 2
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- 240000002234 Allium sativum Species 0.000 description 2
- 244000144725 Amygdalus communis Species 0.000 description 2
- 235000011437 Amygdalus communis Nutrition 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- 229910000952 Be alloy Inorganic materials 0.000 description 2
- 240000004160 Capsicum annuum Species 0.000 description 2
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000735432 Hydrastis canadensis Species 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108010007859 Lisinopril Proteins 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 description 2
- 240000006365 Vitis vinifera Species 0.000 description 2
- 235000014787 Vitis vinifera Nutrition 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 235000020224 almond Nutrition 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 230000003602 anti-herpes Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000003434 antitussive agent Substances 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 229960004530 benazepril Drugs 0.000 description 2
- VPSRQEHTHIMDQM-FKLPMGAJSA-N benazepril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 VPSRQEHTHIMDQM-FKLPMGAJSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 229960002781 bisoprolol Drugs 0.000 description 2
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000000768 catecholaminergic effect Effects 0.000 description 2
- 229940112822 chewing gum Drugs 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 229940043350 citral Drugs 0.000 description 2
- 229960004362 clorazepate Drugs 0.000 description 2
- XDDJGVMJFWAHJX-UHFFFAOYSA-M clorazepic acid anion Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)[O-])N=C1C1=CC=CC=C1 XDDJGVMJFWAHJX-UHFFFAOYSA-M 0.000 description 2
- 229960004415 codeine phosphate Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229940000425 combination drug Drugs 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- KSMVZQYAVGTKIV-UHFFFAOYSA-N decanal Chemical compound CCCCCCCCCC=O KSMVZQYAVGTKIV-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- SSNZFFBDIMUILS-UHFFFAOYSA-N dodec-2-enal Chemical compound CCCCCCCCCC=CC=O SSNZFFBDIMUILS-UHFFFAOYSA-N 0.000 description 2
- 229960005426 doxepin Drugs 0.000 description 2
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 2
- 229960001596 famotidine Drugs 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000007983 food acid Nutrition 0.000 description 2
- 229960002737 fructose Drugs 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 235000004611 garlic Nutrition 0.000 description 2
- 229960001911 glucosamine hydrochloride Drugs 0.000 description 2
- 235000005679 goldenseal Nutrition 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 206010022437 insomnia Diseases 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 229960002394 lisinopril Drugs 0.000 description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 2
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 2
- 229960003088 loratadine Drugs 0.000 description 2
- 229960004391 lorazepam Drugs 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 2
- 229960003940 naproxen sodium Drugs 0.000 description 2
- 229960000227 nisoldipine Drugs 0.000 description 2
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 2
- 229960004535 oxazepam Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 229960003401 ramipril Drugs 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003760 tallow Substances 0.000 description 2
- 229960002613 tamsulosin Drugs 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 description 1
- DJAHKBBSJCDSOZ-AJLBTXRUSA-N (5z,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one;(5e,9e,13e)-6,10,14,18-tetramethylnonadeca-5,9,13,17-tetraen-2-one Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C/CCC(C)=O.CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CCC(C)=O DJAHKBBSJCDSOZ-AJLBTXRUSA-N 0.000 description 1
- KPJZHOPZRAFDTN-ZRGWGRIASA-N (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)CC)C2)=C3C2=CN(C)C3=C1 KPJZHOPZRAFDTN-ZRGWGRIASA-N 0.000 description 1
- ORKBYCQJWQBPFG-WOMZHKBXSA-N (8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 ORKBYCQJWQBPFG-WOMZHKBXSA-N 0.000 description 1
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RZPZLFIUFMNCLY-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol Chemical compound OC(=O)\C=C\C(O)=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 RZPZLFIUFMNCLY-WLHGVMLRSA-N 0.000 description 1
- GGWBHVILAJZWKJ-CHHCPSLASA-N (z)-1-n'-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethyl]-1-n-methyl-2-nitroethene-1,1-diamine;hydron;chloride Chemical compound Cl.[O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-CHHCPSLASA-N 0.000 description 1
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
- QXKZYKFVUJEGTM-UHFFFAOYSA-N 1-[4-(2-cyclopropyloxyethyl)phenoxy]-3-(dimethylamino)propan-2-ol Chemical compound C1=CC(OCC(O)CN(C)C)=CC=C1CCOC1CC1 QXKZYKFVUJEGTM-UHFFFAOYSA-N 0.000 description 1
- QHZLMUACJMDIAE-SFHVURJKSA-N 1-hexadecanoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)CO QHZLMUACJMDIAE-SFHVURJKSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- HVWGTGTZCBPIOH-UHFFFAOYSA-N 1lambda2-stannole Chemical class [Sn]1C=CC=C1 HVWGTGTZCBPIOH-UHFFFAOYSA-N 0.000 description 1
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
- NYVVVBWEVRSKIU-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide Chemical compound OC(=O)C(O)C(O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 NYVVVBWEVRSKIU-UHFFFAOYSA-N 0.000 description 1
- CBOBADCVMLMQRW-UHFFFAOYSA-N 2,6-dimethyloctanal Chemical compound CCC(C)CCCC(C)C=O CBOBADCVMLMQRW-UHFFFAOYSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- ZGDLVKWIZHHWIR-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N2CCOCC2)N=C1 ZGDLVKWIZHHWIR-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- WFJIVOKAWHGMBH-UHFFFAOYSA-N 4-hexylbenzene-1,3-diol Chemical compound CCCCCCC1=CC=C(O)C=C1O WFJIVOKAWHGMBH-UHFFFAOYSA-N 0.000 description 1
- YUXBNNVWBUTOQZ-UHFFFAOYSA-N 4-phenyltriazine Chemical compound C1=CC=CC=C1C1=CC=NN=N1 YUXBNNVWBUTOQZ-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 241000234282 Allium Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 1
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 235000002283 Capsicum annuum var aviculare Nutrition 0.000 description 1
- 235000013303 Capsicum annuum var. frutescens Nutrition 0.000 description 1
- 235000007862 Capsicum baccatum Nutrition 0.000 description 1
- 235000002284 Capsicum baccatum var baccatum Nutrition 0.000 description 1
- 235000002568 Capsicum frutescens Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- JOATXPAWOHTVSZ-UHFFFAOYSA-N Celiprolol Chemical compound CCN(CC)C(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(C(C)=O)=C1 JOATXPAWOHTVSZ-UHFFFAOYSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 235000019499 Citrus oil Nutrition 0.000 description 1
- 241001672694 Citrus reticulata Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 description 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 description 1
- 235000009685 Crataegus X maligna Nutrition 0.000 description 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 description 1
- 235000009486 Crataegus bullatus Nutrition 0.000 description 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 description 1
- 235000009682 Crataegus limnophila Nutrition 0.000 description 1
- 240000000171 Crataegus monogyna Species 0.000 description 1
- 235000004423 Crataegus monogyna Nutrition 0.000 description 1
- 235000002313 Crataegus paludosa Nutrition 0.000 description 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 244000133098 Echinacea angustifolia Species 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- 241001632410 Eleutherococcus senticosus Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 239000004605 External Lubricant Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- RRJFVPUCXDGFJB-UHFFFAOYSA-N Fexofenadine hydrochloride Chemical compound Cl.C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RRJFVPUCXDGFJB-UHFFFAOYSA-N 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- QYZRTBKYBJRGJB-PCMHIUKPSA-N Granisetron hydrochloride Chemical compound Cl.C1=CC=C2C(C(=O)NC3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 QYZRTBKYBJRGJB-PCMHIUKPSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 229920001908 Hydrogenated starch hydrolysate Polymers 0.000 description 1
- 206010020571 Hyperaldosteronism Diseases 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 235000013628 Lantana involucrata Nutrition 0.000 description 1
- 240000005183 Lantana involucrata Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000220225 Malus Species 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 235000006677 Monarda citriodora ssp. austromontana Nutrition 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 235000010676 Ocimum basilicum Nutrition 0.000 description 1
- 240000007926 Ocimum gratissimum Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- VRSLTNZJOUZKLX-UHFFFAOYSA-N Ondansetron hydrochloride Chemical compound O.O.Cl.CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 VRSLTNZJOUZKLX-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- QHZLMUACJMDIAE-UHFFFAOYSA-N Palmitic acid monoglyceride Natural products CCCCCCCCCCCCCCCC(=O)OCC(O)CO QHZLMUACJMDIAE-UHFFFAOYSA-N 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000003181 Panax pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- 208000037158 Partial Epilepsies Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 235000016787 Piper methysticum Nutrition 0.000 description 1
- 240000005546 Piper methysticum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 240000001987 Pyrus communis Species 0.000 description 1
- IKMPWMZBZSAONZ-UHFFFAOYSA-N Quazepam Chemical compound FC1=CC=CC=C1C1=NCC(=S)N(CC(F)(F)F)C2=CC=C(Cl)C=C12 IKMPWMZBZSAONZ-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- JPRXYLQNJJVCMZ-UHFFFAOYSA-N Rizatriptan benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1.C1=C2C(CC[NH+](C)C)=CNC2=CC=C1CN1C=NC=N1 JPRXYLQNJJVCMZ-UHFFFAOYSA-N 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 235000006092 Stevia rebaudiana Nutrition 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 240000001949 Taraxacum officinale Species 0.000 description 1
- 235000005187 Taraxacum officinale ssp. officinale Nutrition 0.000 description 1
- SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 244000125380 Terminalia tomentosa Species 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 244000078534 Vaccinium myrtillus Species 0.000 description 1
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 1
- ZCDDBUOENGJMLV-QRPNPIFTSA-N Valacyclovir hydrochloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 ZCDDBUOENGJMLV-QRPNPIFTSA-N 0.000 description 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- MWYNOTLRCUQCKD-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(oxolan-2-yl)methanone;hydrate;hydrochloride Chemical compound O.Cl.N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 MWYNOTLRCUQCKD-UHFFFAOYSA-N 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 229940086217 acetaminophen 160 mg Drugs 0.000 description 1
- 229940086240 acetaminophen 325 mg Drugs 0.000 description 1
- 229940086239 acetaminophen 500 mg Drugs 0.000 description 1
- 229940086245 acetaminophen 650 mg Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229960004538 alprazolam Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 1
- 229960004005 amlodipine besylate Drugs 0.000 description 1
- 229960002519 amoxapine Drugs 0.000 description 1
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000002484 anti-cholesterolemic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003561 anti-manic effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000000228 antimanic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 229960004754 astemizole Drugs 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 1
- 229960003277 atazanavir Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960001770 atorvastatin calcium Drugs 0.000 description 1
- 229960004574 azelastine Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- IPOKCKJONYRRHP-FMQUCBEESA-N balsalazide Chemical compound C1=CC(C(=O)NCCC(=O)O)=CC=C1\N=N\C1=CC=C(O)C(C(O)=O)=C1 IPOKCKJONYRRHP-FMQUCBEESA-N 0.000 description 1
- 229960004168 balsalazide Drugs 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- YNKMHABLMGIIFX-UHFFFAOYSA-N benzaldehyde;methane Chemical compound C.O=CC1=CC=CC=C1 YNKMHABLMGIIFX-UHFFFAOYSA-N 0.000 description 1
- 229940054066 benzamide antipsychotics Drugs 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 229960000503 bisacodyl Drugs 0.000 description 1
- 229960005400 bisoprolol fumarate Drugs 0.000 description 1
- 235000013614 black pepper Nutrition 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- SRGKFVAASLQVBO-BTJKTKAUSA-N brompheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 SRGKFVAASLQVBO-BTJKTKAUSA-N 0.000 description 1
- 229960003108 brompheniramine maleate Drugs 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229940085865 calcium carbonate 750 mg Drugs 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- KRALOLGXHLZTCW-UHFFFAOYSA-L calcium;2-acetyloxybenzoate Chemical compound [Ca+2].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O KRALOLGXHLZTCW-UHFFFAOYSA-L 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000001728 capsicum frutescens Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229940077731 carbohydrate nutrients Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000001013 cariogenic effect Effects 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960002320 celiprolol Drugs 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- 229940052311 cerivastatin sodium Drugs 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- 229950006523 cilexetil Drugs 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- WTEVQBCEXWBHNA-YFHOEESVSA-N citral B Natural products CC(C)=CCC\C(C)=C/C=O WTEVQBCEXWBHNA-YFHOEESVSA-N 0.000 description 1
- 239000010500 citrus oil Substances 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229940010007 cobalamins Drugs 0.000 description 1
- 150000001867 cobalamins Chemical class 0.000 description 1
- 235000019879 cocoa butter substitute Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- VTDCYOLLYVAJSY-UHFFFAOYSA-N cyclohexyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC1CCCCC1 VTDCYOLLYVAJSY-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical class C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- HESHRHUZIWVEAJ-JGRZULCMSA-N dihydroergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2[C@@H](C3=CC=CC4=NC=C([C]34)C2)C1)C)C1=CC=CC=C1 HESHRHUZIWVEAJ-JGRZULCMSA-N 0.000 description 1
- 229960004704 dihydroergotamine Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960004192 diphenoxylate Drugs 0.000 description 1
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960000878 docusate sodium Drugs 0.000 description 1
- 229960003218 dolasetron mesylate Drugs 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- VJECBOKJABCYMF-UHFFFAOYSA-N doxazosin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 VJECBOKJABCYMF-UHFFFAOYSA-N 0.000 description 1
- 229960000220 doxazosin mesylate Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960002472 eletriptan Drugs 0.000 description 1
- OTLDLQZJRFYOJR-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC1=CN=C2[C]1C=C(CCS(=O)(=O)C=1C=CC=CC=1)C=C2 OTLDLQZJRFYOJR-LJQANCHMSA-N 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 229960003449 epinastine Drugs 0.000 description 1
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 1
- 229960000573 eprosartan mesylate Drugs 0.000 description 1
- DJSLTDBPKHORNY-XMMWENQYSA-N eprosartan methanesulfonate Chemical compound CS(O)(=O)=O.C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 DJSLTDBPKHORNY-XMMWENQYSA-N 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 1
- 229960004943 ergotamine Drugs 0.000 description 1
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- CDCHDCWJMGXXRH-UHFFFAOYSA-N estazolam Chemical compound C=1C(Cl)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 CDCHDCWJMGXXRH-UHFFFAOYSA-N 0.000 description 1
- 229960002336 estazolam Drugs 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000002171 ethylene diamines Chemical class 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 229940066493 expectorants Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 229960004396 famciclovir Drugs 0.000 description 1
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 229960003528 flurazepam Drugs 0.000 description 1
- SAADBVWGJQAEFS-UHFFFAOYSA-N flurazepam Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F SAADBVWGJQAEFS-UHFFFAOYSA-N 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- 229960000868 fluvastatin sodium Drugs 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 1
- 229960003142 fosamprenavir Drugs 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 239000002843 gaba uptake inhibitor Chemical class 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 229940125695 gastrointestinal agent Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 235000002532 grape seed extract Nutrition 0.000 description 1
- 229940087603 grape seed extract Drugs 0.000 description 1
- 229940095486 guaifenesin 100 mg Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000008131 herbal destillate Substances 0.000 description 1
- 229960003258 hexylresorcinol Drugs 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 239000010514 hydrogenated cottonseed oil Substances 0.000 description 1
- 235000019866 hydrogenated palm kernel oil Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229940072322 hylan Drugs 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 201000010930 hyperostosis Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 229960001195 imidapril Drugs 0.000 description 1
- KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
- 150000005232 imidazopyridines Chemical class 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000000905 isomalt Substances 0.000 description 1
- 235000010439 isomalt Nutrition 0.000 description 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- 229960000519 losartan potassium Drugs 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 229940127021 low-dose drug Drugs 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229960000816 magnesium hydroxide Drugs 0.000 description 1
- 229940007172 magnesium hydroxide 135 mg Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 229940041290 mannose Drugs 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 125000000695 menaquinone group Chemical group 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 229960001186 methysergide Drugs 0.000 description 1
- 229960004503 metoclopramide Drugs 0.000 description 1
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 229960003793 midazolam Drugs 0.000 description 1
- DDLIGBOFAVUZHB-UHFFFAOYSA-N midazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F DDLIGBOFAVUZHB-UHFFFAOYSA-N 0.000 description 1
- 229940029985 mineral supplement Drugs 0.000 description 1
- 235000020786 mineral supplement Nutrition 0.000 description 1
- 229960001785 mirtazapine Drugs 0.000 description 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 235000016337 monopotassium tartrate Nutrition 0.000 description 1
- 230000000510 mucolytic effect Effects 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- UNHGSHHVDNGCFN-UHFFFAOYSA-N naratriptan Chemical compound C=12[CH]C(CCS(=O)(=O)NC)=CC=C2N=CC=1C1CCN(C)CC1 UNHGSHHVDNGCFN-UHFFFAOYSA-N 0.000 description 1
- 229960005254 naratriptan Drugs 0.000 description 1
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
- 229960001800 nefazodone Drugs 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 description 1
- 229960004872 nizatidine Drugs 0.000 description 1
- GYHFUZHODSMOHU-UHFFFAOYSA-N nonanal Chemical compound CCCCCCCCC=O GYHFUZHODSMOHU-UHFFFAOYSA-N 0.000 description 1
- 239000012875 nonionic emulsifier Substances 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 239000002777 nucleoside Chemical class 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020939 nutritional additive Nutrition 0.000 description 1
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000008601 oleoresin Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- SBQLYHNEIUGQKH-UHFFFAOYSA-N omeprazole Chemical compound N1=C2[CH]C(OC)=CC=C2N=C1S(=O)CC1=NC=C(C)C(OC)=C1C SBQLYHNEIUGQKH-UHFFFAOYSA-N 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 229940050957 opium tincture Drugs 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 239000003346 palm kernel oil Substances 0.000 description 1
- 235000019865 palm kernel oil Nutrition 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- GELRVIPPMNMYGS-RVXRQPKJSA-N paroxetine hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 GELRVIPPMNMYGS-RVXRQPKJSA-N 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 229960000964 phenelzine Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 229940071370 phenylephrine 10 mg Drugs 0.000 description 1
- 229940102707 phenylephrine 5 mg Drugs 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 1
- 229920000223 polyglycerol Chemical class 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- VWBQYTRBTXKKOG-IYNICTALSA-M pravastatin sodium Chemical compound [Na+].C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 VWBQYTRBTXKKOG-IYNICTALSA-M 0.000 description 1
- 229960001495 pravastatin sodium Drugs 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 239000011164 primary particle Substances 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 229960002601 protriptyline Drugs 0.000 description 1
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- 150000003834 purine nucleoside derivatives Chemical class 0.000 description 1
- 230000006824 pyrimidine synthesis Effects 0.000 description 1
- 229960001964 quazepam Drugs 0.000 description 1
- 229960001778 rabeprazole sodium Drugs 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004789 rizatriptan benzoate Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 235000014102 seafood Nutrition 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 229940124513 senna glycoside Drugs 0.000 description 1
- 229930186851 sennoside Natural products 0.000 description 1
- IPQVTOJGNYVQEO-KGFNBKMBSA-N sennoside A Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC2=C1C(=O)C1=C(O)C=C(C(O)=O)C=C1[C@@H]2[C@H]1C2=CC(C(O)=O)=CC(O)=C2C(=O)C2=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C=CC=C21 IPQVTOJGNYVQEO-KGFNBKMBSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007944 soluble tablet Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 229960004940 sulpiride Drugs 0.000 description 1
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 1
- 229960000658 sumatriptan succinate Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 229960003188 temazepam Drugs 0.000 description 1
- 229960004084 temocapril Drugs 0.000 description 1
- FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
- LZNWYQJJBLGYLT-UHFFFAOYSA-N tenoxicam Chemical compound OC=1C=2SC=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LZNWYQJJBLGYLT-UHFFFAOYSA-N 0.000 description 1
- 229960002871 tenoxicam Drugs 0.000 description 1
- 229950006156 teprenone Drugs 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 1
- 229960003386 triazolam Drugs 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229960002431 trimipramine Drugs 0.000 description 1
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 1
- ZNRGQMMCGHDTEI-ITGUQSILSA-N tropisetron Chemical compound C1=CC=C2C(C(=O)O[C@H]3C[C@H]4CC[C@@H](C3)N4C)=CNC2=C1 ZNRGQMMCGHDTEI-ITGUQSILSA-N 0.000 description 1
- 229960003688 tropisetron Drugs 0.000 description 1
- QTFFGPOXNNGTGZ-RCSCTSIBSA-N u3c8e5bwkr Chemical compound O.CS(O)(=O)=O.C1=CC=C2C(C(OC3C[C@@H]4CC5C[C@@H](N4CC5=O)C3)=O)=CNC2=C1 QTFFGPOXNNGTGZ-RCSCTSIBSA-N 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 229940093257 valacyclovir Drugs 0.000 description 1
- 229940102566 valproate Drugs 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical group 0.000 description 1
- 150000003714 vitamin K1 derivatives Chemical class 0.000 description 1
- 235000019143 vitamin K2 Nutrition 0.000 description 1
- 239000011728 vitamin K2 Substances 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- 239000001717 vitis vinifera seed extract Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229960000314 zinc acetate Drugs 0.000 description 1
- 229960001360 zolmitriptan Drugs 0.000 description 1
- ULSDMUVEXKOYBU-ZDUSSCGKSA-N zolmitriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C[C@H]1COC(=O)N1 ULSDMUVEXKOYBU-ZDUSSCGKSA-N 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- 229960000820 zopiclone Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
Definitions
- the present invention relates to a rapid-melt composition for delivery of prophylactic and therapeutic active materials to a mammal, methods of making the same, and methods of using the same.
- the prophylactic or therapeutic active is a psychotropic, a gastrointestinal therapeutic or a migraine therapeutic.
- compositions may be produced in a variety of dosage forms, depending upon the desired route of administration of the therapeutic material.
- Oral dosage forms include such solid compositions as tablets, beads/granules, emulsions, and suspensions.
- the particular dosage form utilized will depend on such factors as the solubility and chemical reactivity of the pharmaceutical active. Further, the dosage form may be selected so as to optimize delivery of the pharmaceutical active and/or consumer acceptability of the composition.
- Tablet oral dosage forms compositions offer many advantages, including ease of product handling, chemical and physical stability, portability (in particular, allowing ready availability to the consumer when needed), aesthetic acceptability and dosage precision, i.e., ensuring consistent and accurate dosages of the pharmaceutical active.
- liquid formulations may offer advantages in the treatment of certain disorders, such as disorders of the upper gastrointestinal tract, wherein delivery of an active material dissolved or dispersed in a liquid ensures rapid and complete delivery to the afflicted area.
- many chewable tablet formulations have been developed.
- oral dosage forms such as chewable tablets, beads, powders, granules
- Many pharmaceutical and confectionery tablets are designed to be chewed either to provide proper flavor or to increase the surface area of a particular drug to permit rapid activity in the digestive tract or circulatory systems.
- many pharmaceutical ingredients usually have both an unpleasant mouth feel and unpalatable taste due to chalkiness, grittiness, dryness and astringent properties of these materials. Accordingly, the practical value of these materials is substantially diminished since patients finding them objectionable may fail to take them as prescribed.
- a number of formulations have been investigated to ease the mouth feel and palatability of such compositions.
- Khankari et al. U.S. Pat. No. 6,024,981 discloses a rapidly dissolving robust dosage form directed to a hard tablet that can be packaged, stored and processed in bulk.
- the solid tablet dissolves in the mouth of a patient with a minimum of grit.
- the tablet contains an active ingredient mixed into a matrix of a non-direct compression filler and a relatively high lubricant content.
- Amselem U.S. Pat. No. 5,989,583, discloses a dry solid lipid composition suitable as an oral dosage form.
- the composition contains a lipophilic substance, at least one fat which is a solid at about 25° C. and at least one phospholipid present in an amount of about 2 to 40% by weight of the composition.
- the resultant product is a dry solid lipid composition.
- United Kingdom patent application GB 2 195 892 discloses pharmaceutical chewable tablets with improved palatability.
- the lipid-containing tablets include a lipid material having a melting point from about 26° C. to about 37° C., a particulate dispersant material, an emulsifier and a safe and effective amount of a pharmaceutically active material.
- the tablets of the lipid composition exhibit improved palatability, and effective dispersion in the mouth and stomach.
- United Kingdom patent application GB 2 195 891 also discloses pharmaceutical chewable tablets with improved palatability.
- the lipid-containing tablets include a lipid material, a dispersant, a nonionic emulsifier having an HLB of at least 10, and a safe and effective amount of a pharmaceutical active material, wherein the average HLB of all emulsifiers in the composition is at least about 8.
- Nakamichi et al. U.S. Pat. No. 5,837,285, discloses fast soluble tablets that can be produced by a simple method.
- the tablet base is a sugar alcohol.
- the mixture of the sugar alcohol and a drug is subjected to compressive shaping prior to drying in the process.
- the dry solid tablet can be produced by modification of conventional tableting technology and possesses physico-chemical stability.
- Chavkin et al. U.S. Pat. No. 5,753,255 discloses a chewable medicinal tablet.
- the tablet contains about 30 to about 95% by weight of a capric triglyceride and a medicinally active ingredient up to 60% by weight. If the medicinally active ingredient is less than about 30% by weight, then the composition also contains up to 10% by weight of a member of the group consisting of glyceryl monostearate, a mixture of glyceryl monostearate and glyceryl monopalmitate, and a mixture of glyceryl monostearate and glyceryl distearate.
- Geyer et al. U.S. Pat. No. 5,320,848, discloses a nonaqueous chewable composition for oral delivery of unpalatable drugs.
- the drug is intimately dispersed or dissolved in a pharmaceutically-acceptable lipid that is solid at room temperatures.
- the lipid material desirably readily melts with the application of mild temperatures, i.e. about 55 to 95 C.
- Lapidus U.S. Pat. No. 4,937,076, discloses a chewable aspirin and buffering material tablet in a single dosage form.
- the buffering materials are integrally dispersed and bound in a fatty material of chocolate, synthetic chocolate or hydrogenated tallow.
- the fatty material individually coats the aspirin and buffering material.
- the tablets have a harder outer shell which inhibits penetration of liquid, and a softer interior which quickly liquefies when the tablet and shell are broken into pieces and contacted by the liquid.
- the excipient or base material of the tablet is made from carbohydrates held together with small quantities of a carbohydrate binder such as maltodextrin.
- the tablets can contain active ingredients such as pharmaceuticals, breath sweeteners, vitamins and dietary supplements.
- the tablet contains solid antacid particles thoroughly coated with a mixture composed of a fatty material or oil, a surfactant, and a flavor.
- the fat or oil is present in an amount of from about 25% to about 45% of the mixture.
- the primary particle size of the antacid is less than 100 millimicrons.
- Puglia et al. U.S. Pat. No. 4,327,077 discloses a compressed chewable antacid tablet which has good flexibility, is breakage resistant and disintegrates immediately upon chewing.
- the tablet is formed of a recrystallized fatty material, such as chocolate, a bulking material and an active ingredient bound up in the particles of the recrystallized fatty material.
- the preferred recrystallized fatty material is a chocolate or a synthetic chocolate.
- Puglia et al. U.S. Pat. No. 4,327,076, also discloses a compressed chewable antacid tablet which has good flexibility, is breakage resistant and disintegrates immediately upon chewing.
- the tablet is formed of particles of the antacid or other active ingredients which are admixed with particles formed of edible fat or oil absorbed on a fat-absorbing material, such as microcrystalline cellulose. Upon chewing, the tablet is quickly converted to a smooth creamy non-gritty palatable emulsion.
- compositions contain various disadvantages.
- tablets may be incompletely chewed due to the poor palatability of the composition.
- Such compositions may also have a gummy texture, and are subject to “taste fatigue,” i.e., the composition is perceived to be less palatable after ingestion of multiple doses.
- the binders and other materials used in such chewable tablets may prevent rapid and effective delivery of active materials to the stomach.
- compositions that behaves like a liquid when consumed by a mammal, and yet acts like a solid in many other ways.
- the need extends for compositions in which little to substantially no biting or chewing is necessary in order for the composition to melt, disintegrate, decompose, or otherwise break down or apart in the mouth of a mammal.
- Such compositions are ideal for uses in the fields of pediatric and geriatric care, that is, for use with people or mammals that do not have any teeth. These compositions are particularly useful for pediatric, geriatric patients or for those with limited ability to swallow traditional dosage forms.
- Applicant has unexpectedly developed a method of preparing a rapid-melt composition comprising the steps of:
- Applicant has further developed a method of preparing a rapid-melt composition comprising the steps of:
- Applicant has unexpected developed a method for preparing a compressed rapid-melt composition comprising the steps of:
- step b) granulating said mixture from step a) to form granules
- the rapid-melt molded compositions of the present inventive subject matter exhibit good resistance to prolonged exposure to beat and the atmosphere. More particularly, the compositions surprisingly maintain their texture and rapid melting properties when exposed to those elements.
- the rapid-melt compositions of the present inventive subject matter contains at least one binder, a salivating agent, an active material, and a diluent/bulking material.
- the rapid-melt compositions may also contain a slipping agent to aid in the transport of the composition from the mouth of the mammal to the stomach thereof.
- mammal includes without limitation any mammalian subject, such as mice, rats, guinea pigs, cats, dogs, human beings, cows, horses, sheep or other livestock.
- free water means water that is not found in other ingredients. Many ingredients used in the present inventive compositions may also have water as part of the ingredient, and the term “free water” refers to water that is separate from those ingredients.
- the unique novel combination of elements allows for fast melting of the composition when placed in the mouth of a user.
- the saliva of the user provides hydration to the composition and allows the composition to melt without any chewing.
- a unique feature of the present inventive compositions is that the composition becomes a liquid upon the application of pressure.
- the compositions rapidly melt upon the application of pressure by the tongue of the patient, thus forming a liquid carrier for the active ingredients contained therein.
- the liquid helps provide the unique characteristics and features of the present inventive compositions.
- the liquification of the inventive compositions can be achieved through the application of pressure by the tongue of the patient, as described above.
- the liquification may be attained by the patient chewing the compositions.
- a slight amount of chewing will enhance the liquification of the compositions.
- a further way for the composition to be liquefied is by the patient sucking on the rapid-melt, compositions of the inventive subject matter.
- the rapid-melt technology of the present inventive subject matter has multiple applications which are ideal for the unique properties of the compositions.
- One such application is the delivery of active ingredients to a mammal in need thereof.
- the melting feature of the novel compositions makes the compositions ideal for uses in pediatric and geriatric care, since small children and aged individuals often have difficulty chewing items.
- the compositions may be specially formulated for pediatric and geriatric patients.
- the unique properties will aid in drug compliance by such patients as the drugs may be administered in a way that will not require chewing by the patient.
- inventive compositions are ideal for enhance the saliva flow of a patient.
- a frequent problem for geriatric patients is dry-mouth, or the inability to salivate sufficiently.
- the aid of saliva flow by the use of the present inventive compositions will enhance tooth cleaning within the patient, as well as stimulate better drug delivery to the patient. Also, the increased saliva flow will facilitate better breath characteristics in the patient.
- the use of xylitol, as well as other polyols and sugars, in the inventive compositions will contribute to the enhancement of the saliva flow of the patient.
- a further application for the inventive compositions would be the preparation of compositions for drug delivery in diabetic patients.
- a diabetic patient must monitor the intake of sugar and the ability to formulate the present inventive compositions with fractose and other non-cariogenic components makes them ideal for delivery of drugs to diabetic patients.
- the rapid-melt compositions of the present inventive subject matter are preferably anhydrous, that is, they do not contain any water.
- the lack of water in the inventive compositions allows high doses of active materials or combinations of active materials to be incorporated into the compositions due to the stability of the active materials in the absence of the water.
- the compositions may optionally include an amount of water.
- the amount of water present will depend on the active ingredients to be delivered, but generally will be present in an amount less than 2.0% by weight of the composition.
- the water will be present in an amount less than 1.0% by weight of the composition.
- the rapid-melt compositions of the present inventive subject matter contain at least one binder.
- binder means at least one ingredient useful in keeping the composition in its state, may be either solid or liquid, and may include, without limitation, a high melting point fat or waxy material such as lipid materials, polyethylene glycols (PEG), waxes and other fats.
- the compositions of the present inventive subject matter contains a mixture of binders.
- the solid binders useful in the compositions of the present inventive subject matter have a melting point of about 25 to 90° C., and preferably about 37° C.
- the melting point of the combination of the binders will remain within the range of 25 to 90° C., and preferably about 37° C.
- the inventive subject matter contemplates the use of mixtures of solid binders and liquid binders.
- the present inventive subject matter contemplates mixing a small amount of a high-melting point lipid with a liquid binder to achieve a binder that attains the desired product characteristics. These characteristics include such factors as mouth feel, rapidity of melting in the mouth, appearance, flavor and compatibility with active materials and therapeutic active materials.
- lipid materials useful as binders in the compositions of the present inventive subject matter are those which are commercially available and commonly used in confectionery and other food products.
- Such lipid materials include, without limitation, cocoa butter, hydrogenated tallow, hydrogenated vegetable oils, hydrogenated cotton seed oil, palm kernel oil, soybean oil, stannol esters, and derivatives and mixtures thereof.
- Hydrogenated vegetable oils (such as hydrogenated palm kernel oil), cocoa butter, and cocoa butter substitutes are among the preferred useful lipid materials.
- Additional binders may include glycerol esters, polyalcohol esters, polyoxyethylelne esters of hydrophilic and hydrophobic balances from 0.5 to above 20 and polyethylene glycols.
- liquid binders examples include saccharides such as monosaccharides and oligosaccharides.
- monosaccahrides include: dextrose, dextrose monohydrate, lactose, mannose, fructose, etc.
- Liquid binders may also be used. Examples of liquid binders are, without limitation, polysaccharides, gum solutions, water, corn syrup, hydrogenated starch hydrolates, glycerine, polypropylene glycol, and mixtures thereof. It should be noted that liquid binders, when used may be present in quantities to not affect the constituency of the product so that the final product retains a predominantly solid constituency. In some aspects, the liquid binders may not exceed about 5% of the composition.
- the amount of binder present in the rapid-melt composition of the present inventive subject matter is from about 0.01% to about 70% by weight of the final composition.
- the amount of binder is from about 0.01% to about 50% by weight of the composition. More preferably the binder is present from about 15% to about 30% by weight of the composition.
- the binder is used to provide good melt away properties to the composition while preventing a gritty texture being imparted by the composition.
- the binder aids in the fast melting of the composition when placed in the mouth of a user.
- the rapid-melt composition of the present inventive subject matter also contains a salivating agent.
- salivating agent means a material that promotes greater salivation in the user of the compositions of the present inventive subject matter.
- the salivating agent helps create salivation in the mouth of the mammal using the inventive compositions. This is an important feature since the present compositions are intended to be taken by the patient without the aid of water to help in the transporting of the composition to the stomach of the patient.
- the salivating agent can be, without limitation, an emulsifier or a food acid that initiates salivation in the mouth of the patient.
- emulsifiers useful as salivating agents in the compositions of the present inventive subject matter include, without limitation, alkyl aryl sulfonates, alkyl sulfates, sulfonated amides and amines, sulfated and sulfonated esters and ethers, alkyl sulfonates, polyethoxylated esters, mono-, di-, and triglycerides, diacetyl tartaric esters of monoglycerides, polyglycerol esters, sorbitan esters and ethoxylates, lactylated esters, phospholipids such as lecithin, polyoxyethylene sorbitan esters, proplyene glycol esters, sucrose esters, and mixtures thereof.
- the emulsifier may be either saturated or unsaturated. It should be noted that some of the emulsifiers that are salivating agents may also function as binders.
- Examples of food acids useful as salivating agents in the inventive compositions include, without limitation, citric acid, malic acid, tartarate, food salts such as sodium chloride and salt substitutes, potassium chloride, and mixtures thereof.
- the amount of salivating agent present in the rapid-melt composition of the present inventive subject matter is from about 0.05% to about 15% by weight of the final composition.
- the amount of salivating agent from about 0.3% to 0.4% by weight of the composition.
- the amount of salivating agent present in the inventive composition within these limits for weight percentage is important to enhance the desirable properties of the compositions. More particularly, the low amount of salivating agent present in the compositions aid in the compositions retaining the physical state and the rapidity of melting in the mouth of a mammal.
- the rapid-melt compositions of the present inventive subject matter further contain a diluent/bulking material.
- a diluent/bulking material is necessary to serve as a free-flow imparting agent which aids in the moisturizing of the composition when chewed, that is, the diluent/bulking material aids in the processability of the compositions.
- the diluent/bulking material also serves to reduce the concentration of the active materials and add bulk to the composition.
- diluent/bulking materials useful in the compositions of the present inventive subject matter include, without limitation, silicon dioxide, sugars, starches, lactose, sucrose, sorbitol, fructose, talc, stearic acid, magnesium stearate, dicalcium phosphate, erythitol, xylitol, mannitol, maltitol, isomalt, dextrose, maltose, lactose, microcrystalline celluloses and mixtures thereof. It should be noted that some of the diluents/bulking materials also function as binders.
- the amount of diluent/bulking material present in the rapid-melt compositions is from about 0.5% to about 99% by weight of the final composition.
- the amount of diluent/bulking material is from about 2% to about 95% by weight of the final composition.
- the rapid-melt compositions of the present inventive subject matter may optionally contain a further slipping agent to aid in the palatability of the composition after it melts in the mouth of the mammal.
- the slipping agent may be a further lipid material, as is described above for binders, or another material which aids in the “slipping” of the composition through the mouth and down the esophagus of the mammal.
- compositions of the present invention may be compressed into tablets or made into granules, beads or particles for direct consumption/administration.
- the granules, beads or particles may be further processed into additional dosage forms such as tablets, capsules, caplets or suspensions and emulsions.
- the preferably anhydrous nature of the present inventive compositions allows for very high doses of active materials to be incorporated therein.
- the amount of active material present in the inventive compositions will vary depending on the particular active used, but generally will be present in an amount of about 0.001% to 70% by weight of the composition.
- the active ingredients used in the inventive compositions are prophylactic or therapeutic active ingredients. Prophylactic or therapeutic active materials which can be used in the present invention are varied.
- a non-limiting list of such materials includes the following: antitussives, antihistamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, antacids, ion exchange resins, anti-cholesterolemics, antiarrhythmics, antipyretics, analgesics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, anti-infectives, psycho-tropics, antimanics, stimulants, gastrointestinal agents, sedatives, antidiarrheal preparations, anti-anginal drugs, vasodialators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, antitumor drugs, anticoagulants, antithrombotic drugs, hypontics, anti-emetics, anti-nausants, anti-convulsants, neuromuscular
- Preferred prophylactic or therapeutic active materials contemplated for use in the present inventive subject matter are analgesics.
- analgesics useful in the present inventive subject matter, and which are the preferred therapeutic active ingredients include, without limitation, aspirin, acetaminophen, ibuprophen and mixtures thereof.
- Another preferred active material can be selected from the class of prophylactic, abortive or analgesic drugs used to treat migraines.
- Migraines are defined as headaches that last 4 to 72 hours wherein the patient experiences moderate to severe cranial throbbing. Migraines are also associated with nausea, vomiting, or sensitivity to light, sound or smell.
- beta.-blockers For prophylactic treatment of migraines, beta.-blockers, calcium channel blockers, tricyclic antidepressants, or anticonvulsants can be used.
- drugs indicated for prophylactic treatment include amitriptyline, methysergide, popranolol, valproate, and verapamil.
- serotonin receptor activators such as eletriptan, ergotamine, naratriptan, rizatriptan benzoate, sumatriptan succinate, and zolmitriptan can be used.
- Ergot alkaloid derivatives such as ergoamine tartrate and dihydroergotamine are also effective.
- Dopamine antagonist anti-emetics such as metoclopramide and prochlorperazine while indicated for the treatment of nausea, can also be used even if nausea is not prominent.
- acetaminophen for analgesic treatment acetaminophen, aspirin, non-asteroidal anti-inflammatory drugs (“NSAID”) and opioids can be used in the present invention.
- NSAID non-asteroidal anti-inflammatory drugs
- a psychotropic is used to treat depression, schizophrenia, anxiety disorders, attention deficit order, obsessive compulsive disorder, senile dementia and certain sleep disorders.
- the classes of drugs used in treating depression include selective serotonin reuptake inhibitors (“SSRI's”), heterocyclic antidepressants, monoamine oxidase inhibitors (“MAOI's”), serotonergic-noradrenergics, 5-HT.sub.2 antagonists and catecholaminergics.
- SSRI'S include fluoxetine HCl, sertraline HCl, paroxetine HCl, and fluvoxamine.
- heterocyclic antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, doxepin, trimipramine, clomipramine, protriptyline, amoxapine, and maprotiline.
- Examples of MAOI's include phenelzine and tranylcypromine.
- An example of a serotonergic-noradrenergi-cs includes venlafaxine HCl.
- Examples of 5-HT.sub.2 antagonists include trazadone, nefazodone, and mirtazapine.
- An example of a catecholaminergics includes bupropion. All examples are non-limiting and it will be understood that psychotropics of the disclosed classes may be used with the present inventive subject matter.
- benzodiazepines may be used with the present inventive subject matter.
- Specific examples include alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam.
- any class of psychotropic drug indicated for anxiety treatment may be used in the present invention.
- drugs belonging to the categories of benzodiazepines, imidazopyridines, antidepressants and non-prescription hypnotics may be used with the present inventive subject matter.
- benzodiazepines useful for the treatment of insomnia include midazolam, triazolam, oxazepam, temazepam, lorazepam, estazolam, nitrazepam, diazepam, quazepam, flurazepam, zopiclone and clorazepate.
- An example of an imidazopyridine includes zolpidem and zolpidem tartarate.
- antidepressants include amityiptyline and doxepin.
- Still yet another preferred active material used in the composition of the present inventive matter is a gastrointestinal therapeutic.
- Gastrointestinal therapeutics are used to treat gastritis, nausea and vomiting, gastroesophegal reflux disease, colitis, Crohn's disease and diarrhea.
- Classes of drugs include proton pump inhibitors, histamine H.sub.2 receptor antagonists, terpene analogs, and NSAID'S.
- drugs such as omeprazole, lansoprazole, ranitidine HCl, famotidine, nizatidine, teprenone, cimetidinc, rabeprazole sodium, and sulpiride can be used in the compositions of the present inventive subject matter.
- drugs such as ondansetron HCl, granisetron HCl, dolasetron mesylate, and tropisetron may be used.
- Cardiovascular therapeutics treat hypertension, angina, myocardial infarction, congestive heart failure, acute coronary syndrome, edema, ventricular tachycardia, hyperaldosteronism, ventricular arrhythmia, cardiac insufficiency, atrial fibrillation, arterial occlusion, cardiac decompensation, and microcirculation activation.
- a related class of cardiovascular therapeutics are cholesterol reducers such as 3-hydroxy-3-methylglutaryl coenzymeA (“HMG-CoA”) reductase inhibitors.
- HMG-CoA inhibitors work by blocking an enzyme used to make cholesterol. Blocking cholesterol thereby treats hypercholesterolemia which is a significant cause of cardiovascular disease.
- drugs such as simvastin, atorvastatin calcium, pravastatin sodium, pravastatin, lovastatin, fluvastatin sodium, cerivastatin sodium can be used in the compositions of the present inventive subject matter.
- drugs such as amlodipine besylate, losartan potassium, lisinopril, felodipine, benazepril HCl, ramipril, irbesartan, verapamil HCl, bisoprolol fumarate and hydrochlorothiazide, amiodipine and benazepril HCl, clonidine, candesartan, cilexetil, diltiazem, nicardipine, imidapril, trandolapril, eprosartan mesylate, nilvadipine, verapamil HCl, temocapril, prazosin HCl, isradipine, cilazapril, celiprolol, bisoprolol, betazolol HCl, ramipril, nisoldipine, lisinopril, trandolapril,
- drugs such as dioxin, carvedilol, spironolactone, trandolapril, and bisoprolol can be used in the compositions of the present inventive subject matter.
- Still another preferred active material used in the composition of the present invention is a therapeutic useful for treating allergic rhinitis.
- the classes of compounds useful for treating allergic rhinitis include alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazine, piperidines, and nonsedating compounds.
- Other drugs which can also be used are fluticasone propionate, mometasone furoate, epinastine, beclomethasone dipropionate, triamcinolone acetonide, budesonide, and azelastine.
- Still yet another preferred active material used in the composition of the present invention is a therapeutic useful for treating osteoarthritis or rheumatoid arthritis.
- Rheumatoid arthritis is defined as non-specific, symmetrical inflammation of the peripheral joints, potentially resulting in progressive destruction of articular and particular structures.
- Osteoarthritis is characterized by loss of articular cartilage and hypertrophy of bone.
- osteoarthritis is a degenerative bone disease
- symptoms associated with rheumatoid arthritis such as inflammation of the joints occur in a patient diagnosed with osteoarthritis. Accordingly, therapeutics treating rheumatoid arthritis can also be administered to an osteoarthritic patient.
- Classes of drugs indicated for osteoarthritis and rheumatoid arthritis include cycloxygenase-2 inhibitors, NSAID'S, biologic response modifiers, pyrimidine synthesis inhibitors and hyaluronic acid.
- Specific examples of osteoarthritis and rheumatoid arthritis therapeutics include celecoxib, diclofenac sodium, rofecoxib, nabumetone, dictlofenac sodium and misoprostol, oxaprozin, meloxicam, piroxicam, etodolac, naproxen, hylan G-F 20, leflunomide, tenoxicam, and naproxen sodium.
- Another preferred active material used in the composition of the present invention is a therapeutic useful for treating benign prostatic hypertrophy.
- Benign prostatic hypertrophy is defined as an adenomatous hyperplasia of the periurethral part of the prostrate gland.
- Classes of drug useful for the treatment of benign prostatic hypertrophy include alpha blockers, alpha-1 selective adrenoceptor blocking agents and 5-reductase inhibitors.
- Specific examples of benign prostatic hypertrophy therapeutics include doxazosin mesylate, terazosin HCl, tamsulosin, finasteride, tamsulosin HCl, ethinyl estradiol and levonorgestrel.
- Yet another preferred active material used in the composition of the present invention is a drug indicated for the treatment of fungal infections.
- Classes of drugs indicated for the treatment of fungal infections include synthetic triazole, ergosterol inhibitor, and polyene antifungal.
- Specific examples of drugs indicated for the treatment of fungal infections are itraconazole, ketoconazole, and amphotericin B.
- Still yet another preferred active material used in the composition of the present invention is a anti-convulsant.
- Anti-convulsants are drugs that prevent or relieve convulsions wherein the convulsions are due to epilepsy, seizure disorders, partial seizure disorders or Huntington's disease.
- Classes of drugs useful for treating these conditions include gamma-aminobutyric analogs, phenyltriazine, antiepileptic agents, benzodiazepines, polysynaptic response inhibitors, sulfamate-substituted monosaccharides, gamma-amino butyric acid uptake inhibitors and benzamides.
- Specific examples include carbamazepine, topiramate, and tigabine HCl mixtures thereof combination drugs.
- Anti-herpetics are used to treat infections from the varicella-zoster virus.
- Classes of drugs useful for treating herpes include synthetic purine nucleoside analogs, nucleoside analogs, and antiviral agents. Specific examples include acyclovir, valacyclovir HCL and famcyclovir mixtures thereof combination drugs.
- Anti-diarrheal therapeutics treat the condition of diarrhea whether it is symptomatic of the disorder itself wherein diarrhea is a condition that occurs when a mammal has a low amount of stool in a bowel movement. Diarrhea results mainly from excess fecal water in the bowel of the mammal.
- Specific examples of anti-diarrheal therapeutics include loperamide HCl, diphenoxylate, codeine phosphate, camphorated opium tincture.
- nutritional active materials useful in the present inventive subject matter include, without limitation, calcium-containing materials such as calcium carbonate, vitamins, minerals, herbals, spices and mixtures thereof.
- vitamins that are available as active ingredients include, without limitation, vitamin A (retinal), vitamin D (cholecalciferol), vitamin E group (a-tocopherol and other tocopherols), vitamin K group (phylloquinones and menaquinones), thiamine (vitamin B.sub.1), riboflavin (vitamin B2), niacin, vitamin B.sub.6 group, folic acid, vitamin B.sub.12 (cobalamins), biotin, vitamin C (ascorbic acid), and mixtures thereof.
- the amount of vitamin or vitamins present in the final encapsulated product of the present inventive subject matter is dependent on the particular vitamin and is generally the United States' Department of Agriculture Recommended Daily Allowances (USRDA) for that vitamin.
- USRDA United States' Department of Agriculture Recommended Daily Allowances
- vitamin C is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults
- the amount of vitamin C in the encapsulated product would be 60 milligrams, which is the USRDA of vitamin C for adults.
- minerals that are available as active ingredients include, without limitation, calcium, magnesium, phosphorus, iron, zinc, iodine, selenium, potassium, copper, manganese, molybdenum and mixtures thereof.
- vitamins the amount of mineral or minerals present in the final encapsulated product of the present inventive subject matter is dependent on the particular mineral and is generally the USRDA for that mineral. For example, if iodine is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults, the amount of iodine in the encapsulated product would be 150 micrograms, which is the USRDA of iodine for adults.
- herbals that are available as active ingredients include, without limitation, echinacea , peppermint, licorice, goldenseal, panax pseudoginseng, grapeseed extract, bilberry, kava, gingko biloba, panax quinquefolium, Siberian ginseng, St. John's wort, bromelian, guglupids, hawthorn, garlic, ginger, angelica species, dandelion, goldenseal, and mixtures thereof.
- examples of spices that are available as active ingredients include, without limitation, mustard, dillweed, cinnamon, garlic, black pepper, onion, sage, oregano, basil, cream of tartar, targon, cayenne pepper, red pepper, and mixtures thereof. This list of herbals and spices is for exemplary purposes and is not meant to be construed as limiting the inventive subject matter thereto.
- the active material may be present in a high dose.
- “high dose” represents a dosage from about 450 mg to about 2000 mg per unit dosage to be administered to a patient.
- the high dose may represent from about 450 mg to about 2000 mg; or from about 450 mg to about 1200 mg; or from about 500 mg to about 1500 mg; or from about 500 mg to about 1200 mg; or from about 600 mg to about 1500 mg; or from about 600 mg to about 1200 mg.
- Such high dose actives may be selected from a variety of therapeutic categories, and include, but not limited to the following: an analgesic; an anti-inflammatory; an antibiotic; an antiviral; an anti-irritability; a mineral, or a nutritional supplement, etc.
- Examples of specific drugs include: aspirin, acetaminophen, naproxen, balsalazide; mesalamine; ampicillin, amoxicillin; clavulanate; azithromycin, clarithromyin, abacavir, lamivudine, acyclovir, atazanavir, efavirenz, fosamprenavir, nelfinavir, ribavirin, saquinavir, and valacyclovir, or a combination thereof.
- vitamin A calcium carbonate
- glucosamine chondroitin
- Vitamin C guaifenesin
- magnesium hydroxide caffeine, loratadine, ibuprofeb, pseudoephedrine, diphenhydramine, chlorpheniramine maleate, cimetidine, ranitidine, famotidine, benzocaine, hexylresorcinol, zinc acetate, zinc gluconate, naproxen, naproxen sodium, codeine phosphate, hydrocodone, brompheniramine maleate, docusate sodium, bisacodyl, sennoside, multivitamins (vitamin A, B1, B2, B6, B12), Vitamin E, alone or in combination with another active agent.
- these active ingredients are encapsulated or coated with a functional or nonfunctional coating, which coated and/or encapsulated ingredients are then used in making the rapid melt compositions.
- a functional or nonfunctional coating Some nonlimiting examples include: encapsulated glucosamine, chondroitin, encapsulated phenylephrine, encapsulated acetaminophen, encapsulated vitamin C, encapsulated guaifenesin, encapsulated aspirin, calcium carbonate, magnesium hydroxide, or a mixture thereof.
- functional coating include enteric coating, pH-dependent coating, sustained release coating.
- nonfunctional coating include film coating and sugar coating.
- compositions with those unpalatable active materials have unpalatable tastes.
- Taste-masking of compositions with those unpalatable active materials is well-known in the art.
- the use of flavors and sweeteners to mask the unpalatability of the active materials is also well-known.
- other materials which can be incorporated into the rapid-melt composition of the present inventive subject matter include flavors, colors and sweeteners.
- a distinct feature of the inventive rapid-melt, compositions is that they exhibit excellent taste characteristics. Importantly, it is possible to incorporate high levels of flavors, sweeteners and other taste-masking agents, making the compositions more palatable when undesirable tastes accompany the active materials.
- Flavors may be chosen from natural and synthetic flavor liquids. Flavors useful in the present inventive compositions include, without limitation, volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof.
- volatile oils such as lemon, orange, grape, lime and grapefruit and fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors.
- aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., betal-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruit), and 2-dodecenal (citrus, mandarin), and mixtures thereof.
- aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., betal-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), al
- flavors useful in the inventive compositions include, without limitation, beef flavorings, chicken flavorings, rice flavorings, lamb flavorings, pork flavorings, seafood flavorings, and mixtures thereof.
- the sweeteners may be chosen from the following non-limiting list: flucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof; saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, zylitol, and the like.
- hydrogenated starch hydrolysates and synthetic sweetener 3,6-dihydro-6-methyl-1-1-1,2,3-oxath-iazin-4-one-2,2-dioxide, particularly the potassium salt (acesulfame-K) and sodium and calcium salts thereof.
- Other sweeteners may also be used.
- the rapid-melt compositions of the present inventive subject matter may also be coated in order to facilitate handling of the compositions. Coatings well-known in the art are useful for keeping the compositions from melting prior to being administered to a patient in need of an active material. By coating the compositions, the composition will maintain its state while being handled and will melt when inserted into a patient's mouth.
- the present inventive subject matter also contemplates a method of preparing a rapid-melt composition.
- a preferred method involves the steps of: melting at least one binder having a melting point about 25 to 90° C. with a salivating agent to form a mixture; mixing an active material with the lipid material to form an active mixture; mixing a diluent/bulking material with said active material to form a final mixture; and molding the final mixture into the composition.
- the method of the present inventive subject matter also contemplates adding other materials to the final mixture prior to molding into the rapid-melt composition. Other materials which may be added to the final mixture prior to molding include, without limitation, flavors, colors, sweeteners, and mixtures thereof.
- the amount of binder melted with the salivating agent is from about 10% to about 70% by weight of the final composition.
- the amount of binder is from about 10% to about 50% by weight. More preferably the binder is present from about 15% to about 30% by weight.
- the amount of salivating agent melted in the first step of the method is from about 0.2% to about 0.5% by weight of the final composition.
- the amount of salivating agent is from about 0.3% to 0.4% by weight of the composition.
- composition may be prepared by a variety of methods well-known by those of ordinary skill in the art. Such processes may be used on a batch or continuous process format and would involve melting the binders and unifonnly blending them for suitable periods of time prior to adding the salivating agent. Once these two components have been blended together, the further components may be added either together or sequentially until a uniform mixture is obtained.
- the Uniform mixture may be poured into a mold, cast into preformed shapes, or stamped into the final products.
- other tableting techniques are contemplated to be used herein.
- the rapid-melt products of the present inventive subject matter are formed via compression of the ingredients.
- the compression of the ingredients into rapid-melt products may take place in a conventional compression or tableting machine such as a punch and die machine.
- the punches used in the punch and die machine may be modified with various materials to limit the formation of a film on the product when the same is punched into shape.
- One such modification would be to make the punch tips from a copper-beryllium alloy.
- the use of the copper-beryllium alloy on the tips of the punch, as well as blowing cold low-humidity air on the punch and dies before filling will aid in the reduction of film formation on the products.
- the external lubrication may be in the form of a powder lubricant applied via electrostatic method, or the external lubricant may be a liquid lubricant which is applied via conventional jet spraying techniques. In any of the above situations, the film formation during compression will be largely negated.
- the binders present in the inventive rapid-melt formulations provide proper binding for the components of the formulation when formed by compression, thus no additional binders or other ingredients are needed.
- the binders already present in the inventive products provide enough binding characteristics that no additional binders are needed for the compression step.
- the fats and emulsifiers acting as the binding agents help form granules that impart flow and compression characteristics in the products.
- the compressed product is exposed to an elevated temperature.
- the conventional way to expose the compressed rapid-melt product is to employ a conveyor belt on which the compressed rapid-melt product is placed. The conveyor belt then passes through a heating zone, in which heat or hot air is applied to the compressed rapid-melt product.
- the interior of the compressed product is preferably not heated as much as the exterior of the compressed product.
- the heat or hot air heats the product or the surface of the product to a temperature of 40 to 60° C. for a period of 1 to 10 minutes.
- the compressed rapid-melt product is heated to a temperature of 45 to 55° C. for a period of 2 to 5 minutes.
- Conventional processes may be employed in order to heat the compressed rapid-melt products, with such conventional processes including, but not limited to, a conventional oven, a high voltage heat lamp, a microwave heating element, or the like.
- a conventional conveyor belt is used in the heating step, preferably the conveyor will be a stainless steel screened type of conveyor. This will allow the heat to be applied to the product from both the top and the bottom.
- the compressed product is slightly heated, causing the emulsifier/fat system to soften or melt within the product.
- This melting results in the semi-liquid binding system changing its configuration in which the void spaces are filled by the softened or melted emulsifier/fat system present in the product.
- the product is cooled to room temperature. Even though the compressed product reaches room temperature relatively quickly, it takes the binding system several hours to return to its original form. This is due to the polymorphism of the emulsifier/fat system.
- the weak binding system due to the relatively poor binding characteristics of the components
- the fats and emulsifiers which may be considered weak binders when the compressed rapid-melt product is first granulated and compressed, the fats and emulsifiers now become a much stronger bonding system.
- the heating step of the inventive process may be done under vacuum, thus enhancing the bonding of the particles by the fat/emulsifier system.
- the friability of the compressed product Due to the relatively weak binding characteristics of the fats and emulsifiers, the compressed rapid-melt product may be friable when first compressed. By surface heating the product and converting the binding system to a bonding system, the compressed product has a much higher integrity which allows it to be easily packaged. In other words, the tablet's friability has decreased significantly from very high to almost nothing. The tablet has a high integrity that is suitable for packaging in any form, including large bottles, and the stability of the compressed product is very good.
- the active ingredient is added to the compressed rapid-melt composition during the lubrication step of the process. That is, the active ingredient is added to the mixture at the same time that the lubricants are added to the mixture.
- the active ingredient is not exposed to the elevated temperatures used to melt the fats and emulsifiers. The lack of exposure to the higher temperature required to melt the fats and emulsifiers helps keep the integrity of the active ingredients intact, meaning that it is less likely for the active ingredients to decompose due to the elevated temperatures.
- lubricants may be water-soluble or non-water-soluble.
- lubricants include magnesium stearate, calcium stearate, talc, starches, silicon dioxide, water soluble lubricants and mixtures thereof.
- the lubricant may be present in an amount from about 0.1% to about 5%. In some aspects, the lubricant may be present in an amount from about 0.2% to about 3%. In another aspect, the lubricant may be present in an amount from about 0.2% to about 2%.
- the compressed rapid-melt product disintegrates quickly in the mouth of the mammal.
- the compressed rapid-melt product disintegrates in less than 20 seconds of being placed in the mammal's mouth, preferably within 10 seconds, and more preferably within 7 seconds. In order to maintain this desired property, it is necessary to compress the components using a low compression force.
- the granules may be prepared with less binding agent than is normally required.
- the binding agent may be present only in enough amounts to convert the granular powders into the proper form for flowing within the compression machine. Applicant has determined that if granules prepared with less than the required amount of binding agent are then mixed with a bonding agent prior to compression with the low compressive pressures, the resultant product has much improved friability and is able to be handled and packaged more easily than those products prepared by the conventional method of tableting, while still maintaining the requisite disintegration time in the mouth of the user.
- the bonding agent promotes good bonding between the particles of the compressed product, thus enhancing the integrity of the compressed product.
- the bonding agent does so by helping reduce the porosity, i.e. increase the density, in the compressed rapid-melt product and creating close bonds between the particles in the compressed rapid-melt products.
- Typical bonding agents include, without limitation, polyethylene glycols in solid form (1450-3000 or more), monoglycerides (40-90% glycerides of vegetable or animal fats), acetylated monoglycerides, hydrocolloidal gums, other emulsifiers or fats and mixtures thereof.
- the amount of bonding agent present in the inventive subject matter is from 5 to 30% by weight. Preferably, the amount of bonding agent is 10 to 15% by weight.
- the compressed rapid-melt products prepared by this embodiment may be subjected to a heat treatment to further enhance the bonding as is discussed above.
- the compressed product is exposed to an elevated temperature.
- the conventional way to expose the compressed rapid-melt product is to employ a conveyor belt on which the compressed rapid-melt product is placed. The conveyor belt then passes through a heating zone, in which heat or hot air is applied to the compressed rapid-melt product. The heat or hot air heats the product to a temperature of 40 to 60° C. for a period of 1 to 10 minutes.
- the compressed rapid-melt product is heated to a temperature of 45 to 55° C. for a period of 2 to 5 minutes.
- Conventional processes may be employed in order to heat the compressed rapid-melt products, with such conventional processes including, but not limited to, a conventional oven, a high voltage heat lamp, a microwave heating element, or the like.
- a conventional conveyor belt is used in the heating step, preferably the conveyor will be a stainless steel screened type of conveyor. This will allow the heat to be applied to the product from both the top and the bottom.
- the compressed product is slightly heated, causing the emulsifier/fat system to soften or melt within the product. This melting results in the semi-liquid binding system changing its configuration in which the void spaces are filled by the granules present in the product.
- the interior of the compressed product is preferably not heated as much as the exterior of the compressed product.
- the product After the compressed product has been sufficiently heated, the product is cooled to room temperature. Even though the compressed product reaches room temperature relatively quickly, it takes the binding system several hours to return to its original form. This is due to the polymorphism of the emulsifier/fat system. During this time, the weak binding system (due to the relatively poor binding characteristics of the components) is converted to a bonding system between the particles in the compressed product. Whereas the fats and emulsifiers are weak binders when the compressed rapid-melt product is first granulated and compressed, the fats and emulsifiers now become a much stronger bonding system.
- the heating step of the inventive process may be done under vacuum, thus enhancing the bonding of the particles by the fat/emulsifier system.
- the rapid-melt compositions of the present inventive subject matter produced by the above methods have increased product integrity and stability.
- the compositions are “storage stable”, meaning that the compositions are stable in the absence of special handling procedures.
- the inventive compositions are stable both prior to packaging and after packaging.
- the inventive compositions maintain their stability and integrity without refrigeration and without humidity controls being implemented during handling, packaging and storing of the products.
- the compositions can be used in most of the current economical packages suitable for a global environment. Further, high temperatures are not needed when processing the inventive compositions. The only heat that needs to be used during processing is to melt the binder prior to mixing with the other elements.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- one active ingredient (chondroitin) was added in the emulsifier melting step, while another active (glucosamine) was added during the lubrication step.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen. The resultant product was then compressed in a conventional compression tableting machine.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- a 5.0% hydrocolloidal gum solution in water was prepared. The solution was mixed well and set aside until free from lumps. In the meantime, 73.40% mannitol powder was blended with 24.6% microcrystalline cellulose and 0.21% color agents. After mixing an appropriate time, the gum solution was added to the mixture in small amounts. Just enough gum solution was added to form small lumps or aggregates. The wet aggregates were passed through a #8 screen.
- the granules were placed on trays and allowed to dry using air heated to greater than 150° F. Once completely dry, the granules were ground to a #40 mesh size. The granules were then loaded into a conventional tableting machine and tablets were produced.
- the resultant tablets were of sufficient hardness and provided proper liquification in the mouth.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- the resulting product exhibited good granular flow as well as good hardness of the final product.
- the product was able to be handled and packaged in a conventional manner.
- the product melted within 25 seconds of being placed in the mouth of a mammal.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- the resulting product exhibited good granular flow as well as good hardness of the final product.
- the product was able to be handled and packaged in a conventional manner. The product melted within 10 seconds of being placed in the mouth of a mammal.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- the resulting product exhibited good granular flow; however, the product was very brittle and easily crumbled when pressed between one's fingers. The product would not have been easily handled or packaged.
- Mono and diglycerides (Durem 117) 7.00%, acetylated monoglycerides (Myvacet) 7.00%, (both as salivating agents) 0.05% color agent, 0.2% sucralose, 2.25% citric acid (also as a salivating agent), 51.28% encapsulated glucosamine, and 400 mg chondroitin sulfate were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while citric acid 2.25% was added under continual stirring, along with 1.0% powdered flavors.
- Encapsulated glucosamine comprised of glucosamine HCl, distilled mono and diglycerides as binders and emulsifiers and silicon dioxide as lubricant. Encapsulation was accomplished by heating the distilled mono- and di-glycerides to about 70 C and adding glucosamine with thorough mixing at about 82 C. The mixture was then allowed to cool slowly while adding the lubricant. At about 40 C, taste-masked encapsulated glucosamine was
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- Example 8 The process of Example 8 was followed with the following changes: encapsulated glucosamine HCl comprising 500 mg active and representing 90.5% of the composition. Dextrose monohydrate is at 2.45% by weight of the composition. The preparation was made into bead forms which were then compressed into tablets.
- Mono and diglycerides (Durem 117) 12.00%, acetylated monoglycerides (Myvacet) 7.00%, 0.03% color agent, 0.25% sucralose, distilled monoglycerides, 5.0%, polyethyleneglycol 3350, 4.0%, and 62.5% calcium carbonate were mixed in a heating vessel. Ihe mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 1.0% powdered flavors were added under continual stirring.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- the above formulation is dose-proportional.
- 1250 mg calcium carbonate high-dose product can be made by using the above formulation with ingredients adjusted accordingly.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- the sieved mixture is made into granules or beads (without compression) for administration or for further processing.
- Polysorbate-80 (0.1%), sodium lauryl sulphate (0.05%) and PEG 8000 (1.5%) 0.02% color agent, and 25% encapsulated acetaminophen, 0.75% sucralose were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 0.20% powdered flavors were added under continuous stirring.
- the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- the sieved mixture is made into granules or beads (without compression) for administration or for further processing.
- Example 12 The process of Example 12 was used with the following changes: encapsulated acetaminophen (39.7%); dextrose monohydrate 48%; PEG 8000 (2.0%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.5%).
- Example 12 The process of Example 12 was used with the following changes: encapsulated acetaminophen (23.62%); dextrose monohydrate (53%); PEG 8000 (1.5%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.5%); citric acid (0.65%).
- Example 12 The process of Example 12 was used with the following changes: encapsulated guaifenesin (31%), wherein the encapsulation was 54%; dextrose monohydrate (42%); PEG 3350 (2.1%); polysorbate 80 (0.2%) sodium lauryl sulfate (0.0035%); polyvinylpyrrolidone (Polyplasdone XL-10) (1.4
- Example 12 The process of Example 12 was used with the following changes: encapsulated phenylephrine HCl (10.5%); dextrose monohydrate (47%); PEG 8000 (1.0%); polysorbate 80 (0.26%); sodium lauryl sulfate (0.05%); polyvinylpyrrolidone (Polyplasdone XL-10) (4.0%); sodium starch glycolate (3.44%).
- Example 11 The process of Example 11 was used with the following changes: encapsulated phenylephrine HCl (1.65%); encapsulated acetaminophen (35.75%); dextrose monohydrate (35%); PEG 8000 (2.0%); polysorbate 80 (0.1%); sodium lauryl sulfate (0.05%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.0%).
- Example 12 The process of Example 12 was used with the following changes: encapsulated Vitamin C (91.63%); dextrose monohydrate (3.1%); carnuba wax (14%) of the encapsulated Vitamin C composition; mono- and di-glycerides with acetylated monoglycerides (38% of the encapsulated Vitamin C composition); polyvinylpyrrolidone (Polyplasdone XL-10) (4.0%); sodium starch glycolate (3.44%).
- Example 12 The process of Example 12 was used with the following changes: calcium carbonate (50%); magnesium hydroxide (9.0%); acetylated monodiglycerides (7.0%); mono- and diglycerides (7.0%); PEG 3350 (3.0%).
Abstract
A novel rapid-melt composition, including methods of making the same, and methods of using the same for the delivery of prophylactic and therapeutic active materials to a mammal. The rapid-melt compositions are formed by molding or compression, with an additional heating step being preferred.
Description
- This application is a continuation of U.S. patent application Ser. No. 11/818,212, filed Jun. 12, 2007, which is a continuation-in-part of U.S. patent application Ser. No. 10/208,877, filed Aug. 1, 2002, which is a continuation-in-part of U.S. patent application Ser. No. 09/898,471, filed Jul. 5, 2001, now issued as U.S. Pat. No. 6,406,717, which is a continuation-in-part of U.S. patent application Ser. No. 09/858,885, filed May 17, 2001, now issued as U.S. Pat. No. 6,589,556, which is a continuation-in-part of U.S. patent application Ser. No. 09/610,489, filed Jul. 5, 2000, now issued as U.S. Pat. No. 6,375,982, each of which are incorporated herein by reference.
- The present invention relates to a rapid-melt composition for delivery of prophylactic and therapeutic active materials to a mammal, methods of making the same, and methods of using the same. Preferably, the prophylactic or therapeutic active is a psychotropic, a gastrointestinal therapeutic or a migraine therapeutic.
- Pharmaceutical compositions may be produced in a variety of dosage forms, depending upon the desired route of administration of the therapeutic material. Oral dosage forms, for example, include such solid compositions as tablets, beads/granules, emulsions, and suspensions. The particular dosage form utilized will depend on such factors as the solubility and chemical reactivity of the pharmaceutical active. Further, the dosage form may be selected so as to optimize delivery of the pharmaceutical active and/or consumer acceptability of the composition.
- Tablet oral dosage forms compositions offer many advantages, including ease of product handling, chemical and physical stability, portability (in particular, allowing ready availability to the consumer when needed), aesthetic acceptability and dosage precision, i.e., ensuring consistent and accurate dosages of the pharmaceutical active. However, liquid formulations may offer advantages in the treatment of certain disorders, such as disorders of the upper gastrointestinal tract, wherein delivery of an active material dissolved or dispersed in a liquid ensures rapid and complete delivery to the afflicted area. In an effort to obtain the therapeutic advantages associated with liquid formulations as well as the broad advantages associated with solids, many chewable tablet formulations have been developed.
- One important factor in formulating oral dosage forms such as chewable tablets, beads, powders, granules, is palatability and mouth feel, especially in tablets that include pharmaceutical dosages. Many pharmaceutical and confectionery tablets are designed to be chewed either to provide proper flavor or to increase the surface area of a particular drug to permit rapid activity in the digestive tract or circulatory systems. However, many pharmaceutical ingredients usually have both an unpleasant mouth feel and unpalatable taste due to chalkiness, grittiness, dryness and astringent properties of these materials. Accordingly, the practical value of these materials is substantially diminished since patients finding them objectionable may fail to take them as prescribed. A number of formulations have been investigated to ease the mouth feel and palatability of such compositions.
- Khankari et al., U.S. Pat. No. 6,024,981, discloses a rapidly dissolving robust dosage form directed to a hard tablet that can be packaged, stored and processed in bulk. The solid tablet dissolves in the mouth of a patient with a minimum of grit. The tablet contains an active ingredient mixed into a matrix of a non-direct compression filler and a relatively high lubricant content.
- Amselem, U.S. Pat. No. 5,989,583, discloses a dry solid lipid composition suitable as an oral dosage form. The composition contains a lipophilic substance, at least one fat which is a solid at about 25° C. and at least one phospholipid present in an amount of about 2 to 40% by weight of the composition. However, the resultant product is a dry solid lipid composition.
- United Kingdom patent application GB 2 195 892 discloses pharmaceutical chewable tablets with improved palatability. The lipid-containing tablets include a lipid material having a melting point from about 26° C. to about 37° C., a particulate dispersant material, an emulsifier and a safe and effective amount of a pharmaceutically active material. The tablets of the lipid composition exhibit improved palatability, and effective dispersion in the mouth and stomach.
- United Kingdom patent application GB 2 195 891 also discloses pharmaceutical chewable tablets with improved palatability. The lipid-containing tablets include a lipid material, a dispersant, a nonionic emulsifier having an HLB of at least 10, and a safe and effective amount of a pharmaceutical active material, wherein the average HLB of all emulsifiers in the composition is at least about 8.
- Nakamichi et al., U.S. Pat. No. 5,837,285, discloses fast soluble tablets that can be produced by a simple method. The tablet base is a sugar alcohol. The mixture of the sugar alcohol and a drug is subjected to compressive shaping prior to drying in the process. The dry solid tablet can be produced by modification of conventional tableting technology and possesses physico-chemical stability.
- Chavkin et al., U.S. Pat. No. 5,753,255 discloses a chewable medicinal tablet. The tablet contains about 30 to about 95% by weight of a capric triglyceride and a medicinally active ingredient up to 60% by weight. If the medicinally active ingredient is less than about 30% by weight, then the composition also contains up to 10% by weight of a member of the group consisting of glyceryl monostearate, a mixture of glyceryl monostearate and glyceryl monopalmitate, and a mixture of glyceryl monostearate and glyceryl distearate.
- Geyer et al., U.S. Pat. No. 5,320,848, discloses a nonaqueous chewable composition for oral delivery of unpalatable drugs. The drug is intimately dispersed or dissolved in a pharmaceutically-acceptable lipid that is solid at room temperatures. The lipid material desirably readily melts with the application of mild temperatures, i.e. about 55 to 95 C.
- Lapidus, U.S. Pat. No. 4,937,076, discloses a chewable aspirin and buffering material tablet in a single dosage form. The buffering materials are integrally dispersed and bound in a fatty material of chocolate, synthetic chocolate or hydrogenated tallow. The fatty material individually coats the aspirin and buffering material.
- Valentine, U.S. Pat. No. 4,684,534, discloses quick-liquefying, chewable tablets. The tablets have a harder outer shell which inhibits penetration of liquid, and a softer interior which quickly liquefies when the tablet and shell are broken into pieces and contacted by the liquid. The excipient or base material of the tablet is made from carbohydrates held together with small quantities of a carbohydrate binder such as maltodextrin. The tablets can contain active ingredients such as pharmaceuticals, breath sweeteners, vitamins and dietary supplements.
- Morris et al., U.S. Pat. No. 4,609,543, discloses a soft homogeneous antacid tablet. The tablet contains solid antacid particles thoroughly coated with a mixture composed of a fatty material or oil, a surfactant, and a flavor. The fat or oil is present in an amount of from about 25% to about 45% of the mixture. The primary particle size of the antacid is less than 100 millimicrons.
- Fountaine, U.S. Pat. No. 4,446,135, discloses chewable calcium carbonate-containing antacid tablets having good mouth feel properties. The good mouth feel properties of the tablet are obtained by using calcium carbonate of a particular particle size in combination with certain excipients. The calcium carbonate is present in an effective amount and has a size from about 5 to 50 microns in diameter.
- Puglia et al., U.S. Pat. No. 4,327,077, discloses a compressed chewable antacid tablet which has good flexibility, is breakage resistant and disintegrates immediately upon chewing. The tablet is formed of a recrystallized fatty material, such as chocolate, a bulking material and an active ingredient bound up in the particles of the recrystallized fatty material. The preferred recrystallized fatty material is a chocolate or a synthetic chocolate.
- Puglia et al., U.S. Pat. No. 4,327,076, also discloses a compressed chewable antacid tablet which has good flexibility, is breakage resistant and disintegrates immediately upon chewing. The tablet is formed of particles of the antacid or other active ingredients which are admixed with particles formed of edible fat or oil absorbed on a fat-absorbing material, such as microcrystalline cellulose. Upon chewing, the tablet is quickly converted to a smooth creamy non-gritty palatable emulsion.
- However, the prior art compositions contain various disadvantages. For example, tablets may be incompletely chewed due to the poor palatability of the composition. Such compositions may also have a gummy texture, and are subject to “taste fatigue,” i.e., the composition is perceived to be less palatable after ingestion of multiple doses. Further, the binders and other materials used in such chewable tablets may prevent rapid and effective delivery of active materials to the stomach.
- There is a need for a rapid-melt, composition that behaves like a liquid when consumed by a mammal, and yet acts like a solid in many other ways. The need extends for compositions in which little to substantially no biting or chewing is necessary in order for the composition to melt, disintegrate, decompose, or otherwise break down or apart in the mouth of a mammal. Such compositions are ideal for uses in the fields of pediatric and geriatric care, that is, for use with people or mammals that do not have any teeth. These compositions are particularly useful for pediatric, geriatric patients or for those with limited ability to swallow traditional dosage forms.
- It has been found that product formulations containing one or more certain lipid materials, emulsifiers and particulate materials are highly palatable and effective compositions for the delivery of pharmaceutical active materials. Such compositions afford better taste, mouth feel and storage stability than those compositions known in the art
- Applicant has unexpectedly developed a method of preparing a rapid-melt composition comprising the steps of:
- a) melting at least one binder in an amount from about 0.01% to about 70% by weight with a salivating agent in an amount from about 0.05% to about 15% by weight, to form a first mixture;
- b) mixing a therapeutically effective amount of an active ingredient with at least one lubricant to form a second mixture;
- c) combining said first mixture with said second mixture to form a compressible mixture; and
- d) compressing said compressible mixture into said rapid-melt composition.
- Applicant has further developed a method of preparing a rapid-melt composition comprising the steps of:
- a) melting at least one binder in an amount from about 0.01% to about 70% by weight with a salivating agent in an amount from about 0.05% to about 15% by weight, to form a first mixture;
- b) mixing a therapeutically effective amount of an active ingredient with at least one lubricant to form a second mixture;
- c) combining said first mixture with said second mixture to form a compressible mixture;
- d) compressing said compressible mixture into said rapid-melt composition;
- e) heating said rapid-melt composition to a temperature 40 to 60° C. for a period of 1 to 10 minutes in order to convert said binder to a bonding agent; and
- f) cooling said heated rapid-melt composition.
- Further, Applicant has unexpected developed a method for preparing a compressed rapid-melt composition comprising the steps of:
- a) mixing at least one diluent present in an amount of 0.1 to 99%, which is good for low dose drugs, by weight with a therapeutically effective amount of an active ingredient and a binding agent in an amount which is less than required to fully bind said diluent and said active ingredient;
- b) granulating said mixture from step a) to form granules;
- c) mixing said granules with a bonding agent in an amount of 5 to 30% by weight to form a compressible mixture; and
- d) compressing said compressible mixture into said rapid-melt composition.
- The rapid-melt molded compositions of the present inventive subject matter exhibit good resistance to prolonged exposure to beat and the atmosphere. More particularly, the compositions surprisingly maintain their texture and rapid melting properties when exposed to those elements.
- The rapid-melt compositions of the present inventive subject matter contains at least one binder, a salivating agent, an active material, and a diluent/bulking material. The rapid-melt compositions may also contain a slipping agent to aid in the transport of the composition from the mouth of the mammal to the stomach thereof.
- As used herein, the expression “mammal” includes without limitation any mammalian subject, such as mice, rats, guinea pigs, cats, dogs, human beings, cows, horses, sheep or other livestock.
- As used herein, the expression “free water” means water that is not found in other ingredients. Many ingredients used in the present inventive compositions may also have water as part of the ingredient, and the term “free water” refers to water that is separate from those ingredients.
- The unique novel combination of elements allows for fast melting of the composition when placed in the mouth of a user. By pressing the composition between the tongue and cheek of the user, the saliva of the user provides hydration to the composition and allows the composition to melt without any chewing. A unique feature of the present inventive compositions is that the composition becomes a liquid upon the application of pressure. The compositions rapidly melt upon the application of pressure by the tongue of the patient, thus forming a liquid carrier for the active ingredients contained therein. The liquid helps provide the unique characteristics and features of the present inventive compositions.
- The liquification of the inventive compositions can be achieved through the application of pressure by the tongue of the patient, as described above. Optionally, the liquification may be attained by the patient chewing the compositions. A slight amount of chewing will enhance the liquification of the compositions. A further way for the composition to be liquefied is by the patient sucking on the rapid-melt, compositions of the inventive subject matter.
- The rapid-melt technology of the present inventive subject matter has multiple applications which are ideal for the unique properties of the compositions. One such application is the delivery of active ingredients to a mammal in need thereof.
- In addition, the melting feature of the novel compositions makes the compositions ideal for uses in pediatric and geriatric care, since small children and aged individuals often have difficulty chewing items. With this intended use in mind, the compositions may be specially formulated for pediatric and geriatric patients. The unique properties will aid in drug compliance by such patients as the drugs may be administered in a way that will not require chewing by the patient.
- Another application for which the inventive compositions are ideal is to enhance the saliva flow of a patient. A frequent problem for geriatric patients is dry-mouth, or the inability to salivate sufficiently. The aid of saliva flow by the use of the present inventive compositions will enhance tooth cleaning within the patient, as well as stimulate better drug delivery to the patient. Also, the increased saliva flow will facilitate better breath characteristics in the patient. The use of xylitol, as well as other polyols and sugars, in the inventive compositions will contribute to the enhancement of the saliva flow of the patient.
- A further application for the inventive compositions would be the preparation of compositions for drug delivery in diabetic patients. A diabetic patient must monitor the intake of sugar and the ability to formulate the present inventive compositions with fractose and other non-cariogenic components makes them ideal for delivery of drugs to diabetic patients.
- The rapid-melt compositions of the present inventive subject matter are preferably anhydrous, that is, they do not contain any water. The lack of water in the inventive compositions allows high doses of active materials or combinations of active materials to be incorporated into the compositions due to the stability of the active materials in the absence of the water. It is contemplated, however, that the compositions may optionally include an amount of water. The amount of water present will depend on the active ingredients to be delivered, but generally will be present in an amount less than 2.0% by weight of the composition. Preferably, the water will be present in an amount less than 1.0% by weight of the composition.
- The rapid-melt compositions of the present inventive subject matter contain at least one binder. As used herein, “binder” means at least one ingredient useful in keeping the composition in its state, may be either solid or liquid, and may include, without limitation, a high melting point fat or waxy material such as lipid materials, polyethylene glycols (PEG), waxes and other fats. Preferably, the compositions of the present inventive subject matter contains a mixture of binders. The solid binders useful in the compositions of the present inventive subject matter have a melting point of about 25 to 90° C., and preferably about 37° C. When more than one binder is used in the inventive compositions, the melting point of the combination of the binders will remain within the range of 25 to 90° C., and preferably about 37° C. The inventive subject matter contemplates the use of mixtures of solid binders and liquid binders. For a non-limiting example, the present inventive subject matter contemplates mixing a small amount of a high-melting point lipid with a liquid binder to achieve a binder that attains the desired product characteristics. These characteristics include such factors as mouth feel, rapidity of melting in the mouth, appearance, flavor and compatibility with active materials and therapeutic active materials.
- Among the lipid materials useful as binders in the compositions of the present inventive subject matter are those which are commercially available and commonly used in confectionery and other food products. Such lipid materials include, without limitation, cocoa butter, hydrogenated tallow, hydrogenated vegetable oils, hydrogenated cotton seed oil, palm kernel oil, soybean oil, stannol esters, and derivatives and mixtures thereof. Hydrogenated vegetable oils (such as hydrogenated palm kernel oil), cocoa butter, and cocoa butter substitutes are among the preferred useful lipid materials. Additional binders may include glycerol esters, polyalcohol esters, polyoxyethylelne esters of hydrophilic and hydrophobic balances from 0.5 to above 20 and polyethylene glycols. Other examples include saccharides such as monosaccharides and oligosaccharides. Examples of monosaccahrides include: dextrose, dextrose monohydrate, lactose, mannose, fructose, etc. Liquid binders may also be used. Examples of liquid binders are, without limitation, polysaccharides, gum solutions, water, corn syrup, hydrogenated starch hydrolates, glycerine, polypropylene glycol, and mixtures thereof. It should be noted that liquid binders, when used may be present in quantities to not affect the constituency of the product so that the final product retains a predominantly solid constituency. In some aspects, the liquid binders may not exceed about 5% of the composition.
- The amount of binder present in the rapid-melt composition of the present inventive subject matter is from about 0.01% to about 70% by weight of the final composition. Preferably, the amount of binder is from about 0.01% to about 50% by weight of the composition. More preferably the binder is present from about 15% to about 30% by weight of the composition.
- The binder is used to provide good melt away properties to the composition while preventing a gritty texture being imparted by the composition. The binder aids in the fast melting of the composition when placed in the mouth of a user.
- The rapid-melt composition of the present inventive subject matter also contains a salivating agent. As is used herein, “salivating agent” means a material that promotes greater salivation in the user of the compositions of the present inventive subject matter. The salivating agent helps create salivation in the mouth of the mammal using the inventive compositions. This is an important feature since the present compositions are intended to be taken by the patient without the aid of water to help in the transporting of the composition to the stomach of the patient. The salivating agent can be, without limitation, an emulsifier or a food acid that initiates salivation in the mouth of the patient.
- Examples of emulsifiers useful as salivating agents in the compositions of the present inventive subject matter include, without limitation, alkyl aryl sulfonates, alkyl sulfates, sulfonated amides and amines, sulfated and sulfonated esters and ethers, alkyl sulfonates, polyethoxylated esters, mono-, di-, and triglycerides, diacetyl tartaric esters of monoglycerides, polyglycerol esters, sorbitan esters and ethoxylates, lactylated esters, phospholipids such as lecithin, polyoxyethylene sorbitan esters, proplyene glycol esters, sucrose esters, and mixtures thereof. The emulsifier may be either saturated or unsaturated. It should be noted that some of the emulsifiers that are salivating agents may also function as binders.
- Examples of food acids useful as salivating agents in the inventive compositions include, without limitation, citric acid, malic acid, tartarate, food salts such as sodium chloride and salt substitutes, potassium chloride, and mixtures thereof.
- The amount of salivating agent present in the rapid-melt composition of the present inventive subject matter is from about 0.05% to about 15% by weight of the final composition. Preferably, the amount of salivating agent from about 0.3% to 0.4% by weight of the composition.
- Keeping the amount of salivating agent present in the inventive composition within these limits for weight percentage is important to enhance the desirable properties of the compositions. More particularly, the low amount of salivating agent present in the compositions aid in the compositions retaining the physical state and the rapidity of melting in the mouth of a mammal.
- The rapid-melt compositions of the present inventive subject matter further contain a diluent/bulking material. The use of a diluent/bulking material is necessary to serve as a free-flow imparting agent which aids in the moisturizing of the composition when chewed, that is, the diluent/bulking material aids in the processability of the compositions. The diluent/bulking material also serves to reduce the concentration of the active materials and add bulk to the composition. Examples of diluent/bulking materials useful in the compositions of the present inventive subject matter include, without limitation, silicon dioxide, sugars, starches, lactose, sucrose, sorbitol, fructose, talc, stearic acid, magnesium stearate, dicalcium phosphate, erythitol, xylitol, mannitol, maltitol, isomalt, dextrose, maltose, lactose, microcrystalline celluloses and mixtures thereof. It should be noted that some of the diluents/bulking materials also function as binders.
- The amount of diluent/bulking material present in the rapid-melt compositions is from about 0.5% to about 99% by weight of the final composition. Preferably, the amount of diluent/bulking material is from about 2% to about 95% by weight of the final composition.
- The rapid-melt compositions of the present inventive subject matter may optionally contain a further slipping agent to aid in the palatability of the composition after it melts in the mouth of the mammal. The slipping agent may be a further lipid material, as is described above for binders, or another material which aids in the “slipping” of the composition through the mouth and down the esophagus of the mammal.
- The compositions of the present invention may be compressed into tablets or made into granules, beads or particles for direct consumption/administration. The granules, beads or particles may be further processed into additional dosage forms such as tablets, capsules, caplets or suspensions and emulsions.
- As discussed above, the preferably anhydrous nature of the present inventive compositions allows for very high doses of active materials to be incorporated therein. The amount of active material present in the inventive compositions will vary depending on the particular active used, but generally will be present in an amount of about 0.001% to 70% by weight of the composition. Preferably, the active ingredients used in the inventive compositions are prophylactic or therapeutic active ingredients. Prophylactic or therapeutic active materials which can be used in the present invention are varied. A non-limiting list of such materials includes the following: antitussives, antihistamines, decongestants, alkaloids, mineral supplements, laxatives, vitamins, antacids, ion exchange resins, anti-cholesterolemics, antiarrhythmics, antipyretics, analgesics, appetite suppressants, expectorants, anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances, coronary dilators, cerebral dilators, peripheral vasodilators, anti-infectives, psycho-tropics, antimanics, stimulants, gastrointestinal agents, sedatives, antidiarrheal preparations, anti-anginal drugs, vasodialators, anti-hypertensive drugs, vasoconstrictors, migraine treatments, antibiotics, tranquilizers, anti-psychotics, antitumor drugs, anticoagulants, antithrombotic drugs, hypontics, anti-emetics, anti-nausants, anti-convulsants, neuromuscular drugs, hyper- and hypoglycemic spasmodics, uterine relaxants, mineral and nutritional additives, antiobesity drugs, anabolic drugs, erythropoetic drugs, antiashmatics, cough suppressants, mucolytics, anti-uricemic drugs and mixtures thereof.
- Preferred prophylactic or therapeutic active materials contemplated for use in the present inventive subject matter are analgesics. Examples of analgesics useful in the present inventive subject matter, and which are the preferred therapeutic active ingredients, include, without limitation, aspirin, acetaminophen, ibuprophen and mixtures thereof.
- Another preferred active material can be selected from the class of prophylactic, abortive or analgesic drugs used to treat migraines. Migraines are defined as headaches that last 4 to 72 hours wherein the patient experiences moderate to severe cranial throbbing. Migraines are also associated with nausea, vomiting, or sensitivity to light, sound or smell.
- For prophylactic treatment of migraines, beta.-blockers, calcium channel blockers, tricyclic antidepressants, or anticonvulsants can be used. Examples of drugs indicated for prophylactic treatment include amitriptyline, methysergide, popranolol, valproate, and verapamil.
- For abortive treatment of migraines serotonin receptor activators such as eletriptan, ergotamine, naratriptan, rizatriptan benzoate, sumatriptan succinate, and zolmitriptan can be used. Ergot alkaloid derivatives such as ergoamine tartrate and dihydroergotamine are also effective. Dopamine antagonist anti-emetics such as metoclopramide and prochlorperazine while indicated for the treatment of nausea, can also be used even if nausea is not prominent.
- For analgesic treatment acetaminophen, aspirin, non-asteroidal anti-inflammatory drugs (“NSAID”) and opioids can be used in the present invention.
- Yet another preferred active material used in the composition of the present inventive matter is a psychotropic. Psychotropics are used to treat depression, schizophrenia, anxiety disorders, attention deficit order, obsessive compulsive disorder, senile dementia and certain sleep disorders.
- The classes of drugs used in treating depression include selective serotonin reuptake inhibitors (“SSRI's”), heterocyclic antidepressants, monoamine oxidase inhibitors (“MAOI's”), serotonergic-noradrenergics, 5-HT.sub.2 antagonists and catecholaminergics. Examples of SSRI'S include fluoxetine HCl, sertraline HCl, paroxetine HCl, and fluvoxamine. Examples of heterocyclic antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, doxepin, trimipramine, clomipramine, protriptyline, amoxapine, and maprotiline. Examples of MAOI's include phenelzine and tranylcypromine. An example of a serotonergic-noradrenergi-cs includes venlafaxine HCl. Examples of 5-HT.sub.2 antagonists include trazadone, nefazodone, and mirtazapine. An example of a catecholaminergics includes bupropion. All examples are non-limiting and it will be understood that psychotropics of the disclosed classes may be used with the present inventive subject matter.
- For the treatment of anxiety, benzodiazepines may be used with the present inventive subject matter. Specific examples include alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, and oxazepam. However, any class of psychotropic drug indicated for anxiety treatment may be used in the present invention.
- For the treatment of insomnia, drugs belonging to the categories of benzodiazepines, imidazopyridines, antidepressants and non-prescription hypnotics may be used with the present inventive subject matter. Examples of benzodiazepines useful for the treatment of insomnia include midazolam, triazolam, oxazepam, temazepam, lorazepam, estazolam, nitrazepam, diazepam, quazepam, flurazepam, zopiclone and clorazepate. An example of an imidazopyridine includes zolpidem and zolpidem tartarate. Examples of antidepressants include amityiptyline and doxepin.
- Still yet another preferred active material used in the composition of the present inventive matter is a gastrointestinal therapeutic. Gastrointestinal therapeutics are used to treat gastritis, nausea and vomiting, gastroesophegal reflux disease, colitis, Crohn's disease and diarrhea. Classes of drugs include proton pump inhibitors, histamine H.sub.2 receptor antagonists, terpene analogs, and NSAID'S.
- For the treatment of gastritis, drugs such as omeprazole, lansoprazole, ranitidine HCl, famotidine, nizatidine, teprenone, cimetidinc, rabeprazole sodium, and sulpiride can be used in the compositions of the present inventive subject matter.
- For the treatment of nausea and vomiting, drugs such as ondansetron HCl, granisetron HCl, dolasetron mesylate, and tropisetron may be used.
- Another preferred active material used in the compositions of the present invention include cardiovascular therapeutics. Cardiovascular therapeutics treat hypertension, angina, myocardial infarction, congestive heart failure, acute coronary syndrome, edema, ventricular tachycardia, hyperaldosteronism, ventricular arrhythmia, cardiac insufficiency, atrial fibrillation, arterial occlusion, cardiac decompensation, and microcirculation activation.
- A related class of cardiovascular therapeutics are cholesterol reducers such as 3-hydroxy-3-methylglutaryl coenzymeA (“HMG-CoA”) reductase inhibitors. HMG-COA inhibitors work by blocking an enzyme used to make cholesterol. Blocking cholesterol thereby treats hypercholesterolemia which is a significant cause of cardiovascular disease.
- For the treatment of hypercholesterolemia, drugs such as simvastin, atorvastatin calcium, pravastatin sodium, pravastatin, lovastatin, fluvastatin sodium, cerivastatin sodium can be used in the compositions of the present inventive subject matter.
- For the treatment of hypertension, drugs such as amlodipine besylate, losartan potassium, lisinopril, felodipine, benazepril HCl, ramipril, irbesartan, verapamil HCl, bisoprolol fumarate and hydrochlorothiazide, amiodipine and benazepril HCl, clonidine, candesartan, cilexetil, diltiazem, nicardipine, imidapril, trandolapril, eprosartan mesylate, nilvadipine, verapamil HCl, temocapril, prazosin HCl, isradipine, cilazapril, celiprolol, bisoprolol, betazolol HCl, ramipril, nisoldipine, lisinopril, trandolapril, and nisoldipine can be used in the compositions of the present inventive subject matter.
- For the treatment of congestive heart failure, drugs such as dioxin, carvedilol, spironolactone, trandolapril, and bisoprolol can be used in the compositions of the present inventive subject matter.
- Still another preferred active material used in the composition of the present invention is a therapeutic useful for treating allergic rhinitis. The classes of compounds useful for treating allergic rhinitis include alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazine, piperidines, and nonsedating compounds.
- Among the non-sedating compounds that can be used in the present invention are loratadine, fexofenadine HCl, certirizine HCl, and astemizole. Other drugs which can also be used are fluticasone propionate, mometasone furoate, epinastine, beclomethasone dipropionate, triamcinolone acetonide, budesonide, and azelastine.
- Still yet another preferred active material used in the composition of the present invention is a therapeutic useful for treating osteoarthritis or rheumatoid arthritis. Rheumatoid arthritis is defined as non-specific, symmetrical inflammation of the peripheral joints, potentially resulting in progressive destruction of articular and particular structures. Osteoarthritis is characterized by loss of articular cartilage and hypertrophy of bone. Although osteoarthritis is a degenerative bone disease, symptoms associated with rheumatoid arthritis such as inflammation of the joints occur in a patient diagnosed with osteoarthritis. Accordingly, therapeutics treating rheumatoid arthritis can also be administered to an osteoarthritic patient.
- Classes of drugs indicated for osteoarthritis and rheumatoid arthritis include cycloxygenase-2 inhibitors, NSAID'S, biologic response modifiers, pyrimidine synthesis inhibitors and hyaluronic acid. Specific examples of osteoarthritis and rheumatoid arthritis therapeutics include celecoxib, diclofenac sodium, rofecoxib, nabumetone, dictlofenac sodium and misoprostol, oxaprozin, meloxicam, piroxicam, etodolac, naproxen, hylan G-F 20, leflunomide, tenoxicam, and naproxen sodium.
- Another preferred active material used in the composition of the present invention is a therapeutic useful for treating benign prostatic hypertrophy. Benign prostatic hypertrophy is defined as an adenomatous hyperplasia of the periurethral part of the prostrate gland.
- Classes of drug useful for the treatment of benign prostatic hypertrophy include alpha blockers, alpha-1 selective adrenoceptor blocking agents and 5-reductase inhibitors. Specific examples of benign prostatic hypertrophy therapeutics include doxazosin mesylate, terazosin HCl, tamsulosin, finasteride, tamsulosin HCl, ethinyl estradiol and levonorgestrel.
- Yet another preferred active material used in the composition of the present invention is a drug indicated for the treatment of fungal infections. Classes of drugs indicated for the treatment of fungal infections include synthetic triazole, ergosterol inhibitor, and polyene antifungal. Specific examples of drugs indicated for the treatment of fungal infections are itraconazole, ketoconazole, and amphotericin B.
- Still yet another preferred active material used in the composition of the present invention is a anti-convulsant. Anti-convulsants are drugs that prevent or relieve convulsions wherein the convulsions are due to epilepsy, seizure disorders, partial seizure disorders or Huntington's disease. Classes of drugs useful for treating these conditions include gamma-aminobutyric analogs, phenyltriazine, antiepileptic agents, benzodiazepines, polysynaptic response inhibitors, sulfamate-substituted monosaccharides, gamma-amino butyric acid uptake inhibitors and benzamides. Specific examples include carbamazepine, topiramate, and tigabine HCl mixtures thereof combination drugs.
- Another preferred active material used in the composition of the present invention is an anti-herpetic. Anti-herpetics are used to treat infections from the varicella-zoster virus. Classes of drugs useful for treating herpes include synthetic purine nucleoside analogs, nucleoside analogs, and antiviral agents. Specific examples include acyclovir, valacyclovir HCL and famcyclovir mixtures thereof combination drugs.
- Yet another active material used in the compositions of the present invention are anti-diarrheal therapeutics. Anti-diarrheal therapeutics treat the condition of diarrhea whether it is symptomatic of the disorder itself wherein diarrhea is a condition that occurs when a mammal has a low amount of stool in a bowel movement. Diarrhea results mainly from excess fecal water in the bowel of the mammal. Specific examples of anti-diarrheal therapeutics include loperamide HCl, diphenoxylate, codeine phosphate, camphorated opium tincture.
- Further preferred nutritional active materials useful in the present inventive subject matter include, without limitation, calcium-containing materials such as calcium carbonate, vitamins, minerals, herbals, spices and mixtures thereof.
- Examples of vitamins that are available as active ingredients include, without limitation, vitamin A (retinal), vitamin D (cholecalciferol), vitamin E group (a-tocopherol and other tocopherols), vitamin K group (phylloquinones and menaquinones), thiamine (vitamin B.sub.1), riboflavin (vitamin B2), niacin, vitamin B.sub.6 group, folic acid, vitamin B.sub.12 (cobalamins), biotin, vitamin C (ascorbic acid), and mixtures thereof. The amount of vitamin or vitamins present in the final encapsulated product of the present inventive subject matter is dependent on the particular vitamin and is generally the United States' Department of Agriculture Recommended Daily Allowances (USRDA) for that vitamin. For example, if vitamin C is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults, the amount of vitamin C in the encapsulated product would be 60 milligrams, which is the USRDA of vitamin C for adults.
- Examples of minerals that are available as active ingredients include, without limitation, calcium, magnesium, phosphorus, iron, zinc, iodine, selenium, potassium, copper, manganese, molybdenum and mixtures thereof. As is the case with vitamins, the amount of mineral or minerals present in the final encapsulated product of the present inventive subject matter is dependent on the particular mineral and is generally the USRDA for that mineral. For example, if iodine is the active ingredient and the encapsulated product is being used in a confectionery or chewing gum targeting adults, the amount of iodine in the encapsulated product would be 150 micrograms, which is the USRDA of iodine for adults.
- Examples of herbals that are available as active ingredients include, without limitation, echinacea, peppermint, licorice, goldenseal, panax pseudoginseng, grapeseed extract, bilberry, kava, gingko biloba, panax quinquefolium, Siberian ginseng, St. John's wort, bromelian, guglupids, hawthorn, garlic, ginger, angelica species, dandelion, goldenseal, and mixtures thereof. Further, examples of spices that are available as active ingredients include, without limitation, mustard, dillweed, cinnamon, garlic, black pepper, onion, sage, oregano, basil, cream of tartar, targon, cayenne pepper, red pepper, and mixtures thereof. This list of herbals and spices is for exemplary purposes and is not meant to be construed as limiting the inventive subject matter thereto.
- In some aspects, the active material may be present in a high dose. As described herein, “high dose” represents a dosage from about 450 mg to about 2000 mg per unit dosage to be administered to a patient. In some aspects, the high dose may represent from about 450 mg to about 2000 mg; or from about 450 mg to about 1200 mg; or from about 500 mg to about 1500 mg; or from about 500 mg to about 1200 mg; or from about 600 mg to about 1500 mg; or from about 600 mg to about 1200 mg. Such high dose actives may be selected from a variety of therapeutic categories, and include, but not limited to the following: an analgesic; an anti-inflammatory; an antibiotic; an antiviral; an anti-irritability; a mineral, or a nutritional supplement, etc. Examples of specific drugs include: aspirin, acetaminophen, naproxen, balsalazide; mesalamine; ampicillin, amoxicillin; clavulanate; azithromycin, clarithromyin, abacavir, lamivudine, acyclovir, atazanavir, efavirenz, fosamprenavir, nelfinavir, ribavirin, saquinavir, and valacyclovir, or a combination thereof. Other examples include: calcium carbonate, glucosamine, chondroitin, Vitamin C, guaifenesin, magnesium hydroxide, caffeine, loratadine, ibuprofeb, pseudoephedrine, diphenhydramine, chlorpheniramine maleate, cimetidine, ranitidine, famotidine, benzocaine, hexylresorcinol, zinc acetate, zinc gluconate, naproxen, naproxen sodium, codeine phosphate, hydrocodone, brompheniramine maleate, docusate sodium, bisacodyl, sennoside, multivitamins (vitamin A, B1, B2, B6, B12), Vitamin E, alone or in combination with another active agent. In some aspects, these active ingredients are encapsulated or coated with a functional or nonfunctional coating, which coated and/or encapsulated ingredients are then used in making the rapid melt compositions. Some nonlimiting examples include: encapsulated glucosamine, chondroitin, encapsulated phenylephrine, encapsulated acetaminophen, encapsulated vitamin C, encapsulated guaifenesin, encapsulated aspirin, calcium carbonate, magnesium hydroxide, or a mixture thereof. Examples of functional coating include enteric coating, pH-dependent coating, sustained release coating. Examples of nonfunctional coating include film coating and sugar coating.
- Many of the active material listed above have unpalatable tastes. Taste-masking of compositions with those unpalatable active materials is well-known in the art. The use of flavors and sweeteners to mask the unpalatability of the active materials is also well-known. Thus, other materials which can be incorporated into the rapid-melt composition of the present inventive subject matter include flavors, colors and sweeteners. A distinct feature of the inventive rapid-melt, compositions is that they exhibit excellent taste characteristics. Importantly, it is possible to incorporate high levels of flavors, sweeteners and other taste-masking agents, making the compositions more palatable when undesirable tastes accompany the active materials.
- Flavors may be chosen from natural and synthetic flavor liquids. Flavors useful in the present inventive compositions include, without limitation, volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts derived from plants, leaves, flowers, fruits, stems and combinations thereof. A non-limiting list of examples include citrus oils such as lemon, orange, grape, lime and grapefruit and fruit essences including apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors.
- Other useful flavorings include aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., betal-citral (lemon, lime), decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruit), and 2-dodecenal (citrus, mandarin), and mixtures thereof.
- Further examples of flavors useful in the inventive compositions include, without limitation, beef flavorings, chicken flavorings, rice flavorings, lamb flavorings, pork flavorings, seafood flavorings, and mixtures thereof.
- The sweeteners may be chosen from the following non-limiting list: flucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof; saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, zylitol, and the like. Also contemplated are hydrogenated starch hydrolysates and synthetic sweetener 3,6-dihydro-6-methyl-1-1-1,2,3-oxath-iazin-4-one-2,2-dioxide, particularly the potassium salt (acesulfame-K) and sodium and calcium salts thereof. Other sweeteners may also be used.
- The rapid-melt compositions of the present inventive subject matter may also be coated in order to facilitate handling of the compositions. Coatings well-known in the art are useful for keeping the compositions from melting prior to being administered to a patient in need of an active material. By coating the compositions, the composition will maintain its state while being handled and will melt when inserted into a patient's mouth.
- The present inventive subject matter also contemplates a method of preparing a rapid-melt composition. A preferred method involves the steps of: melting at least one binder having a melting point about 25 to 90° C. with a salivating agent to form a mixture; mixing an active material with the lipid material to form an active mixture; mixing a diluent/bulking material with said active material to form a final mixture; and molding the final mixture into the composition. The method of the present inventive subject matter also contemplates adding other materials to the final mixture prior to molding into the rapid-melt composition. Other materials which may be added to the final mixture prior to molding include, without limitation, flavors, colors, sweeteners, and mixtures thereof.
- The amount of binder melted with the salivating agent is from about 10% to about 70% by weight of the final composition. Preferably, the amount of binder is from about 10% to about 50% by weight. More preferably the binder is present from about 15% to about 30% by weight. Likewise, the amount of salivating agent melted in the first step of the method is from about 0.2% to about 0.5% by weight of the final composition. Preferably, the amount of salivating agent is from about 0.3% to 0.4% by weight of the composition.
- However, it should be recognized that the composition may be prepared by a variety of methods well-known by those of ordinary skill in the art. Such processes may be used on a batch or continuous process format and would involve melting the binders and unifonnly blending them for suitable periods of time prior to adding the salivating agent. Once these two components have been blended together, the further components may be added either together or sequentially until a uniform mixture is obtained. The Uniform mixture may be poured into a mold, cast into preformed shapes, or stamped into the final products. Clearly, other tableting techniques are contemplated to be used herein.
- In a preferred embodiment, the rapid-melt products of the present inventive subject matter are formed via compression of the ingredients. The compression of the ingredients into rapid-melt products may take place in a conventional compression or tableting machine such as a punch and die machine. In addition, the punches used in the punch and die machine may be modified with various materials to limit the formation of a film on the product when the same is punched into shape. One such modification would be to make the punch tips from a copper-beryllium alloy. The use of the copper-beryllium alloy on the tips of the punch, as well as blowing cold low-humidity air on the punch and dies before filling will aid in the reduction of film formation on the products.
- Further, additional external lubrication could be added to the punch and die machine while forming the products. The external lubrication may be in the form of a powder lubricant applied via electrostatic method, or the external lubricant may be a liquid lubricant which is applied via conventional jet spraying techniques. In any of the above situations, the film formation during compression will be largely negated.
- The binders present in the inventive rapid-melt formulations provide proper binding for the components of the formulation when formed by compression, thus no additional binders or other ingredients are needed. In other words, the binders already present in the inventive products provide enough binding characteristics that no additional binders are needed for the compression step. The fats and emulsifiers acting as the binding agents help form granules that impart flow and compression characteristics in the products.
- In a particularly preferred embodiment, after the inventive rapid-melt product has been compressed, the compressed product is exposed to an elevated temperature. The conventional way to expose the compressed rapid-melt product is to employ a conveyor belt on which the compressed rapid-melt product is placed. The conveyor belt then passes through a heating zone, in which heat or hot air is applied to the compressed rapid-melt product. The interior of the compressed product is preferably not heated as much as the exterior of the compressed product. The heat or hot air heats the product or the surface of the product to a temperature of 40 to 60° C. for a period of 1 to 10 minutes. Preferably, the compressed rapid-melt product is heated to a temperature of 45 to 55° C. for a period of 2 to 5 minutes.
- Conventional processes may be employed in order to heat the compressed rapid-melt products, with such conventional processes including, but not limited to, a conventional oven, a high voltage heat lamp, a microwave heating element, or the like. If a conventional conveyor belt is used in the heating step, preferably the conveyor will be a stainless steel screened type of conveyor. This will allow the heat to be applied to the product from both the top and the bottom.
- In this preferred heating step, the compressed product is slightly heated, causing the emulsifier/fat system to soften or melt within the product. This melting results in the semi-liquid binding system changing its configuration in which the void spaces are filled by the softened or melted emulsifier/fat system present in the product. After the compressed product has been sufficiently heated, the product is cooled to room temperature. Even though the compressed product reaches room temperature relatively quickly, it takes the binding system several hours to return to its original form. This is due to the polymorphism of the emulsifier/fat system. During this time, the weak binding system (due to the relatively poor binding characteristics of the components) is converted to a bonding system between the particles in the compressed product. In this way, the fats and emulsifiers which may be considered weak binders when the compressed rapid-melt product is first granulated and compressed, the fats and emulsifiers now become a much stronger bonding system.
- Optionally, the heating step of the inventive process may be done under vacuum, thus enhancing the bonding of the particles by the fat/emulsifier system.
- One physical characteristic of the compressed rapid-melt product that is changed due to the bonding of the particles by the melted fat/emulsifier system is the friability of the compressed product. Due to the relatively weak binding characteristics of the fats and emulsifiers, the compressed rapid-melt product may be friable when first compressed. By surface heating the product and converting the binding system to a bonding system, the compressed product has a much higher integrity which allows it to be easily packaged. In other words, the tablet's friability has decreased significantly from very high to almost nothing. The tablet has a high integrity that is suitable for packaging in any form, including large bottles, and the stability of the compressed product is very good.
- In a further preferred embodiment of the present inventive subject matter, the active ingredient is added to the compressed rapid-melt composition during the lubrication step of the process. That is, the active ingredient is added to the mixture at the same time that the lubricants are added to the mixture. By adding the active ingredient with the lubricants, the active ingredient is not exposed to the elevated temperatures used to melt the fats and emulsifiers. The lack of exposure to the higher temperature required to melt the fats and emulsifiers helps keep the integrity of the active ingredients intact, meaning that it is less likely for the active ingredients to decompose due to the elevated temperatures.
- In addition to the fats and emulsifiers in the composition acting as lubricants (as well as binders), other lubricants may be added in order to enhance lubrication. Such lubricants may be water-soluble or non-water-soluble. Non-limiting examples of such lubricants include magnesium stearate, calcium stearate, talc, starches, silicon dioxide, water soluble lubricants and mixtures thereof. The lubricant may be present in an amount from about 0.1% to about 5%. In some aspects, the lubricant may be present in an amount from about 0.2% to about 3%. In another aspect, the lubricant may be present in an amount from about 0.2% to about 2%.
- As stated previously, it is an important aspect of the present inventive subject matter that the compressed rapid-melt product disintegrates quickly in the mouth of the mammal. Preferably, the compressed rapid-melt product disintegrates in less than 20 seconds of being placed in the mammal's mouth, preferably within 10 seconds, and more preferably within 7 seconds. In order to maintain this desired property, it is necessary to compress the components using a low compression force.
- It is well-known in the art of compression that tablets are formed by using hard granules prepared by conventional processes, i.e., wet or dry granulation. In all of the conventional processes, strong binders are used to bind the granules and provide good compression and hard tablets when high compression forces are used. Thus, Applicant has found that using the low compressive forces to traditionally-prepared granules results in a compressed product that tend to be friable and fragile.
- In a preferred embodiment of the present inventive subject matter, the granules may be prepared with less binding agent than is normally required. In general, the binding agent may be present only in enough amounts to convert the granular powders into the proper form for flowing within the compression machine. Applicant has determined that if granules prepared with less than the required amount of binding agent are then mixed with a bonding agent prior to compression with the low compressive pressures, the resultant product has much improved friability and is able to be handled and packaged more easily than those products prepared by the conventional method of tableting, while still maintaining the requisite disintegration time in the mouth of the user.
- The bonding agent promotes good bonding between the particles of the compressed product, thus enhancing the integrity of the compressed product. The bonding agent does so by helping reduce the porosity, i.e. increase the density, in the compressed rapid-melt product and creating close bonds between the particles in the compressed rapid-melt products.
- Typical bonding agents include, without limitation, polyethylene glycols in solid form (1450-3000 or more), monoglycerides (40-90% glycerides of vegetable or animal fats), acetylated monoglycerides, hydrocolloidal gums, other emulsifiers or fats and mixtures thereof. The amount of bonding agent present in the inventive subject matter is from 5 to 30% by weight. Preferably, the amount of bonding agent is 10 to 15% by weight.
- Optionally, the compressed rapid-melt products prepared by this embodiment may be subjected to a heat treatment to further enhance the bonding as is discussed above. In particular, the compressed product is exposed to an elevated temperature. The conventional way to expose the compressed rapid-melt product is to employ a conveyor belt on which the compressed rapid-melt product is placed. The conveyor belt then passes through a heating zone, in which heat or hot air is applied to the compressed rapid-melt product. The heat or hot air heats the product to a temperature of 40 to 60° C. for a period of 1 to 10 minutes. Preferably, the compressed rapid-melt product is heated to a temperature of 45 to 55° C. for a period of 2 to 5 minutes.
- Conventional processes may be employed in order to heat the compressed rapid-melt products, with such conventional processes including, but not limited to, a conventional oven, a high voltage heat lamp, a microwave heating element, or the like. If a conventional conveyor belt is used in the heating step, preferably the conveyor will be a stainless steel screened type of conveyor. This will allow the heat to be applied to the product from both the top and the bottom.
- In this preferred heating step, the compressed product is slightly heated, causing the emulsifier/fat system to soften or melt within the product. This melting results in the semi-liquid binding system changing its configuration in which the void spaces are filled by the granules present in the product. The interior of the compressed product is preferably not heated as much as the exterior of the compressed product.
- After the compressed product has been sufficiently heated, the product is cooled to room temperature. Even though the compressed product reaches room temperature relatively quickly, it takes the binding system several hours to return to its original form. This is due to the polymorphism of the emulsifier/fat system. During this time, the weak binding system (due to the relatively poor binding characteristics of the components) is converted to a bonding system between the particles in the compressed product. Whereas the fats and emulsifiers are weak binders when the compressed rapid-melt product is first granulated and compressed, the fats and emulsifiers now become a much stronger bonding system.
- Optionally, the heating step of the inventive process may be done under vacuum, thus enhancing the bonding of the particles by the fat/emulsifier system.
- The rapid-melt compositions of the present inventive subject matter produced by the above methods have increased product integrity and stability. The compositions are “storage stable”, meaning that the compositions are stable in the absence of special handling procedures. The inventive compositions are stable both prior to packaging and after packaging. Importantly, the inventive compositions maintain their stability and integrity without refrigeration and without humidity controls being implemented during handling, packaging and storing of the products. Additionally, since the compositions exhibit increased integrity and stability, the compositions can be used in most of the current economical packages suitable for a global environment. Further, high temperatures are not needed when processing the inventive compositions. The only heat that needs to be used during processing is to melt the binder prior to mixing with the other elements.
- The following examples are illustrative of preferred embodiments of the invention and are not to be construed as limiting the invention thereto. All percentages are given in weight percent, unless otherwise noted and are based on 100% by weight of the final compositions.
- 4.51% cocoa butter, 9.01% sorbitan monostearate, 0.45% lecithin, 0.36% polysorbate 20, 0.45% sodium lauryl sulfate, 0.02% color agent, 0.02% sucralose, 1.62% citric acid and 7.03% chondroitin sulfate were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 34.05% of xylitol powder was added under continual stirring, along with 2.53% powdered flavors pre-blended with 9.01% xylitol powder.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 24.61% encapsulated glucosamine, 4.51% maltodextrin, 0.45% silicon dioxide, 0.90% magnesium stearate, 0.45% additional powdered flavors, and 0.02% color agent were mixed, then passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tabteting machine.
- In this example, one active ingredient (chondroitin) was added in the emulsifier melting step, while another active (glucosamine) was added during the lubrication step.
- 9.5% acetylated monoglycerides, 17.7% hydrogenated vegetable oil and 3.0% monoglycerides were mixed in a suitable vessel and heated to 150° F. to melt the fats. Meanwhile, 68.7% glucosamine hydrochloride powder was pre-blended with 0.8% aspartame and 0.3% sodium laurel sulfate. Once the fats had completely melted, the pre-blended glucosamine hydrochloride mixture was added to the vessel. The fats/glucosamine mixture was them mixed well at 150° F.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen. The resultant product was then compressed in a conventional compression tableting machine.
- 18.80% hydrogenated vegetable oil, 9.68% monoglycerides, 0.48% polysorbate 80, 0.06% sodium lauryl sulfate and 0.02% color agent were mixed and heated in a suitable vessel. The mixture was heated to 130° F. for 10 minutes until the components melted into a solution. 48.76% dextrose powder was added to the mixture under constant stirring along with a pre-blended mixture of 0.04% cooling agent and 1.55% flavors in 12.1% dextrose powder.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 0.28% aspertame, 1.22% powdered flavors, 1.47% silicon dioxide, 1.22% magnesium stearate, 0.6% polyethylene glycol, 3.7% maltodextrin and 0.02% color agents were mixed and passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tableting machine
- Preparation of Cellulose-Containing Compressed Rapid-Melt Product with a Bonding Agent
- A 5.0% hydrocolloidal gum solution in water was prepared. The solution was mixed well and set aside until free from lumps. In the meantime, 73.40% mannitol powder was blended with 24.6% microcrystalline cellulose and 0.21% color agents. After mixing an appropriate time, the gum solution was added to the mixture in small amounts. Just enough gum solution was added to form small lumps or aggregates. The wet aggregates were passed through a #8 screen.
- After sieving, the granules were placed on trays and allowed to dry using air heated to greater than 150° F. Once completely dry, the granules were ground to a #40 mesh size. The granules were then loaded into a conventional tableting machine and tablets were produced.
- The resultant tablets were of sufficient hardness and provided proper liquification in the mouth.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- Following granulation of the mannitol, 77.98% of the above mannitol granules were mixed with 0.20% sucrose, 0.05% sodium lauryl sulphate and 0.07% carboxamide. 1.85% suitable flavors and 6.98% encapsulated active ingredients were added to the mixture. Following proper mixing of the mannitol granules with the remaining above ingredients, 10.20% bonding agent, in this case 10.00% sorbitan monostearate and 0.20% Tween 80, along with 1.00% crosspovidone, 0.50% talc, and 0.75% magnesium stearate were added to the mixture. The final mixture was then tableted using 0.75-inch punches.
- The resulting product exhibited good granular flow as well as good hardness of the final product. The product was able to be handled and packaged in a conventional manner. The product melted within 25 seconds of being placed in the mouth of a mammal.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- Following granulation of the mannitol, 79.85% of the above mannitol granules were mixed with 0.20% sucrose, 0.05% sodium lauryl sulphate and 0.07% carboxamide. 1.85% suitable flavors and 6.98% encapsulated active ingredients were added to the mixture. Following proper mixing of the mannitol granules with the remaining above ingredients, 5.00% bonding agent, in this case sorbitan monostearate, and 5.00% talc as a lubricant, along with 1.00% crosspovidone were added to the mixture. The final mixture was then tableted using 0.75-inch punches.
- The resulting product exhibited good granular flow as well as good hardness of the final product. The product was able to be handled and packaged in a conventional manner. The product melted within 10 seconds of being placed in the mouth of a mammal.
- Mannitol granules were prepared by mixing 89.00% mannitol with 10.00% microcrystalline cellulose. The mannitol and microcrystalline cellulose were granulated with 1.00% polyvinyl pyrrolidone.
- Following granulation of the mannitol, 89.95% of the above mannitol granules were mixed with 0.20% sucrose, 0.05% sodium lauryl sulphate and 0.07% carboxamide. 1.85% suitable flavors and 6.98% encapsulated active ingredients were added to the mixture. Following proper mixing of the mannitol granules with the remaining above ingredients 1.00% crosspovidone was added to the mixture. The final mixture was then tableted using 0.75-inch punches.
- The resulting product exhibited good granular flow; however, the product was very brittle and easily crumbled when pressed between one's fingers. The product would not have been easily handled or packaged.
- Mono and diglycerides (Durem 117) 7.00%, acetylated monoglycerides (Myvacet) 7.00%, (both as salivating agents) 0.05% color agent, 0.2% sucralose, 2.25% citric acid (also as a salivating agent), 51.28% encapsulated glucosamine, and 400 mg chondroitin sulfate were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while citric acid 2.25% was added under continual stirring, along with 1.0% powdered flavors. Encapsulated glucosamine comprised of glucosamine HCl, distilled mono and diglycerides as binders and emulsifiers and silicon dioxide as lubricant. Encapsulation was accomplished by heating the distilled mono- and di-glycerides to about 70 C and adding glucosamine with thorough mixing at about 82 C. The mixture was then allowed to cool slowly while adding the lubricant. At about 40 C, taste-masked encapsulated glucosamine was
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 3.55% dextrose, 0.5% silicon dioxide, 0.50% magnesium stearate, 0.45% additional powdered flavors, and 0.02% color agent were mixed, then passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tableting machine.
- The process of Example 8 was followed with the following changes: encapsulated glucosamine HCl comprising 500 mg active and representing 90.5% of the composition. Dextrose monohydrate is at 2.45% by weight of the composition. The preparation was made into bead forms which were then compressed into tablets.
- Preparation of Compressed Rapid-Melt Tablets Containing Calcium Carbonate 625 mg-1250 mg
- Mono and diglycerides (Durem 117) 12.00%, acetylated monoglycerides (Myvacet) 7.00%, 0.03% color agent, 0.25% sucralose, distilled monoglycerides, 5.0%, polyethyleneglycol 3350, 4.0%, and 62.5% calcium carbonate were mixed in a heating vessel. Ihe mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 1.0% powdered flavors were added under continual stirring.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 1.0% maltodextrin, 4.2% microcrystalline cellulose, 0.5% silicon dioxide, 0.50% magnesium stearate, 1.5% additional powdered flavors, and 0.02% color agent were mixed, then passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tableting machine.
- The above formulation is dose-proportional. Thus, 1250 mg calcium carbonate high-dose product can be made by using the above formulation with ingredients adjusted accordingly.
- 7.0% mono- and di-glycerides, 7.0% acetylated monoglycerides, 0.1% polysorbate 80, 0.1% sodium lauryl sulfate, 0.02% color agent, and 59.1% encapsulated acetaminophen, 1.82% encapsulated phenylephrine, and 0.02% sucralose were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 0.20% powdered flavors were added under continuous stirring.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 6.98% maltodextrin, 7.0% polyvinylpyrrolidone, 1.0% magnesium stearate, 0.45% additional powdered flavors, and 0.01% color agent were mixed, then passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tableting machine.
- Alternatively, the sieved mixture is made into granules or beads (without compression) for administration or for further processing.
- Polysorbate-80 (0.1%), sodium lauryl sulphate (0.05%) and PEG 8000 (1.5%) 0.02% color agent, and 25% encapsulated acetaminophen, 0.75% sucralose were mixed in a heating vessel. The mixture was stirred and heated to a temperature of 130° F. The mixture was maintained at the 130° F. temperature while 0.20% powdered flavors were added under continuous stirring.
- Upon complete blending of the above components, the mixture was transferred to wax paper and cooled to 41° F. for 30 minutes. Once completely cooled, the mixture was milled using a colloidal mill with a #16 screen.
- In the meantime, 37.7% dextrose monohydrate, 7.5% polyvinylpyrrolidone, 0.6% magnesium stearate, 0.45% additional powdered flavors, and 0.01% color agent were mixed, then passed through a #30 mesh.
- After sieving the above mixtures, the two mixtures were blended together and compressed in a conventional compression tableting machine.
- Alternatively, the sieved mixture is made into granules or beads (without compression) for administration or for further processing.
- The process of Example 12 was used with the following changes: encapsulated acetaminophen (39.7%); dextrose monohydrate 48%; PEG 8000 (2.0%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.5%).
- The process of Example 12 was used with the following changes: encapsulated acetaminophen (23.62%); dextrose monohydrate (53%); PEG 8000 (1.5%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.5%); citric acid (0.65%).
- The process of Example 12 was used with the following changes: encapsulated guaifenesin (31%), wherein the encapsulation was 54%; dextrose monohydrate (42%); PEG 3350 (2.1%); polysorbate 80 (0.2%) sodium lauryl sulfate (0.0035%); polyvinylpyrrolidone (Polyplasdone XL-10) (1.4
- Preparation of Compressed Rapid-Melt Tablets Containing phenylephrine HCl 10 mg
- The process of Example 12 was used with the following changes: encapsulated phenylephrine HCl (10.5%); dextrose monohydrate (47%); PEG 8000 (1.0%); polysorbate 80 (0.26%); sodium lauryl sulfate (0.05%); polyvinylpyrrolidone (Polyplasdone XL-10) (4.0%); sodium starch glycolate (3.44%).
- The process of Example 11 was used with the following changes: encapsulated phenylephrine HCl (1.65%); encapsulated acetaminophen (35.75%); dextrose monohydrate (35%); PEG 8000 (2.0%); polysorbate 80 (0.1%); sodium lauryl sulfate (0.05%); polyvinylpyrrolidone (Polyplasdone XL-10) (7.0%).
- The process of Example 12 was used with the following changes: encapsulated Vitamin C (91.63%); dextrose monohydrate (3.1%); carnuba wax (14%) of the encapsulated Vitamin C composition; mono- and di-glycerides with acetylated monoglycerides (38% of the encapsulated Vitamin C composition); polyvinylpyrrolidone (Polyplasdone XL-10) (4.0%); sodium starch glycolate (3.44%).
- The process of Example 12 was used with the following changes: calcium carbonate (50%); magnesium hydroxide (9.0%); acetylated monodiglycerides (7.0%); mono- and diglycerides (7.0%); PEG 3350 (3.0%).
- The inventive subject matter being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the inventive subject matter, and all such modifications are intended to be included within the scope of the following claims.
Claims (26)
1. A rapid-melt compressed solid pharmaceutical composition comprising:
at least one binder in an amount from about 0.01% to about 70% by weight;
a salivating agent in an amount from about 0.05% to about 15% by weight;
a diluent/bulking material in an amount from about 10% to about 90% by weight; and
a mineral salt.
2. The composition of claim 1 , wherein the diluent/bulking material is manitol.
3. The composition of claim 1 , wherein the diluent/bulking material is dextrate.
4. The composition of claim 1 , wherein the mineral salt is zinc acetate.
5. The composition of claim 1 , wherein the mineral salt is zinc gluconate.
6. The composition of claim 1 , further comprising vitamin C.
7. The composition of claim 4 , further comprising Echinacea.
8. The composition of claim 1 , wherein the salivating agent is an emulsifier.
9. The composition of claim 8 , wherein the emulsifier is sodium lauryl sulfate.
10. The composition of claim 8 , wherein the emulsifier is polysorbate 80.
11. The composition of claim 1 , wherein the binder is polyethylene glycol.
12. The composition of claim 1 , wherein the diluent/bulking material further comprising magnesium stearate.
13. The composition of claim 1 , further comprising a sweetener.
14. A rapid-melt compressed solid pharmaceutical composition comprising crosspovidone, mannitol, stearic acid, and a mineral salt.
15. The composition of claim 14 , wherein the mineral salt is zinc acetate.
16. The composition of claim 14 , wherein the mineral salt is zinc gluconate.
17. The composition of claim 14 , further comprising vitamin C.
18. The composition of claim 14 , further comprising Echinacea.
19. The composition of claim 14 , further comprising a sweetener.
20. A rapid-melt compressed solid pharmaceutical composition comprising polyethylene glycol, an emulsifier, a lubricant, and a mineral salt.
21. The composition of claim 20 , wherein the mineral salt is zinc acetate.
22. The composition of claim 20 , wherein the mineral salt is zinc gluconate.
23. The composition of claim 20 , wherein the emulsifier is sodium lauryl sulfate.
24. The composition of claim 20 , wherein the lubricant is magnesium stearate.
25. The composition of claim 20 , further comprising a sweetener.
26. The composition of claim 20 , further comprising a flavoring agent.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/409,574 US20090304824A1 (en) | 2000-07-05 | 2009-03-24 | Rapid-Melt Compositions, Methods of Making Same and Methods of Using Same |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/610,489 US6375982B1 (en) | 2000-07-05 | 2000-07-05 | Rapid-melt semi-solid compositions, methods of making same and method of using same |
US09/858,885 US6589556B2 (en) | 2000-07-05 | 2001-05-17 | Rapid-melt semi-solid compositions, methods of making same and methods of using same |
US09/898,471 US6406717B2 (en) | 2000-07-05 | 2001-07-05 | Rapid-melt semi-solid compositions, methods of making same and methods of using same |
US10/208,877 US7229641B2 (en) | 2000-07-05 | 2002-08-01 | Rapid-melt compositions methods of making same and methods of using same |
US11/818,212 US20080020065A1 (en) | 2000-07-05 | 2007-06-12 | Rapid-melt compositions, methods of making same and method of using same |
US12/409,574 US20090304824A1 (en) | 2000-07-05 | 2009-03-24 | Rapid-Melt Compositions, Methods of Making Same and Methods of Using Same |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/818,212 Continuation US20080020065A1 (en) | 2000-07-05 | 2007-06-12 | Rapid-melt compositions, methods of making same and method of using same |
Publications (1)
Publication Number | Publication Date |
---|---|
US20090304824A1 true US20090304824A1 (en) | 2009-12-10 |
Family
ID=27086265
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/208,877 Expired - Fee Related US7229641B2 (en) | 2000-07-05 | 2002-08-01 | Rapid-melt compositions methods of making same and methods of using same |
US11/818,212 Abandoned US20080020065A1 (en) | 2000-07-05 | 2007-06-12 | Rapid-melt compositions, methods of making same and method of using same |
US12/409,574 Abandoned US20090304824A1 (en) | 2000-07-05 | 2009-03-24 | Rapid-Melt Compositions, Methods of Making Same and Methods of Using Same |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/208,877 Expired - Fee Related US7229641B2 (en) | 2000-07-05 | 2002-08-01 | Rapid-melt compositions methods of making same and methods of using same |
US11/818,212 Abandoned US20080020065A1 (en) | 2000-07-05 | 2007-06-12 | Rapid-melt compositions, methods of making same and method of using same |
Country Status (3)
Country | Link |
---|---|
US (3) | US7229641B2 (en) |
AU (1) | AU2001279284A1 (en) |
WO (1) | WO2002002081A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070243248A1 (en) * | 2006-04-14 | 2007-10-18 | Cherukuri S Rao | Rapidly disintegrating solid oral dosage form of liquid dispersions |
US20070259040A1 (en) * | 2006-05-01 | 2007-11-08 | Cherukuri S R | Novel triptan formulations and methods for making them |
US20080069889A1 (en) * | 2006-03-07 | 2008-03-20 | Cherukuri S R | Compressible resilient granules and formulations prepared therefrom |
US20080081072A1 (en) * | 2006-09-30 | 2008-04-03 | Cherukuri S R | Resin-complex granulation for water-soluble drugs and associated methods |
CN111991440A (en) * | 2020-08-24 | 2020-11-27 | 常州工学院 | Method for extracting flavonoid compounds in cinnamomum camphora by polymer aqueous two-phase extraction |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7364752B1 (en) | 1999-11-12 | 2008-04-29 | Abbott Laboratories | Solid dispersion pharamaceutical formulations |
DE60028754T2 (en) | 1999-11-12 | 2007-05-31 | Abbott Laboratories, Abbott Park | SOLID DISPERSION WITH RITONAVIR, FENOFIBRATE OR GRISEOFULVIN |
DE10026698A1 (en) * | 2000-05-30 | 2001-12-06 | Basf Ag | Self-emulsifying active ingredient formulation and use of this formulation |
US20100010101A1 (en) * | 2000-07-05 | 2010-01-14 | Capricorn Pharma, Inc. | Rapid-Melt Compositions and Methods of Making Same |
WO2002002081A1 (en) * | 2000-07-05 | 2002-01-10 | Capricorn Pharma, Inc. | Rapid-melt semi-solid compositions, methods of making same and methods of using same |
US20030235613A1 (en) * | 2002-06-19 | 2003-12-25 | Cts Chemical Industries Ltd. | Popping oral administration form |
US20080213363A1 (en) * | 2003-01-23 | 2008-09-04 | Singh Nikhilesh N | Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa |
EP1594470A4 (en) * | 2003-02-19 | 2007-10-17 | Biovail Lab Int Srl | Rapid absorption selective 5-ht agonist formulations |
US20050042281A1 (en) * | 2003-08-21 | 2005-02-24 | Singh Nikhilesh N. | Compositions for delivering therapeutic agents across the oral mucosa |
US7390503B1 (en) | 2003-08-22 | 2008-06-24 | Barr Laboratories, Inc. | Ondansetron orally disintegrating tablets |
US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
US20070191815A1 (en) | 2004-09-13 | 2007-08-16 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery |
WO2005118166A2 (en) | 2004-06-04 | 2005-12-15 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical composition containing irbesartan |
US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
US8758816B2 (en) | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
PT2522365T (en) | 2004-11-24 | 2017-02-08 | Meda Pharmaceuticals Inc | Compositions comprising azelastine and methods of use thereof |
US20070020330A1 (en) | 2004-11-24 | 2007-01-25 | Medpointe Healthcare Inc. | Compositions comprising azelastine and methods of use thereof |
US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US8324192B2 (en) | 2005-11-12 | 2012-12-04 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
US8679545B2 (en) | 2005-11-12 | 2014-03-25 | The Regents Of The University Of California | Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract |
US9101160B2 (en) | 2005-11-23 | 2015-08-11 | The Coca-Cola Company | Condiments with high-potency sweetener |
WO2008002529A2 (en) * | 2006-06-26 | 2008-01-03 | Capricorn Pharma, Inc. | Orally disintegrating layered compositions |
US8716200B2 (en) * | 2006-09-13 | 2014-05-06 | Ecolab Usa Inc. | Conveyor lubricants including emulsion of a lipophilic compound and an emulsifier and/or an anionic surfactant and methods employing them |
BRPI0718171A2 (en) | 2006-10-20 | 2013-11-26 | Mcneil Ppc Inc | Acetaminophen / IBUPROPHEN COMBINATIONS AND METHOD FOR USE |
US8017168B2 (en) | 2006-11-02 | 2011-09-13 | The Coca-Cola Company | High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith |
US7718677B2 (en) | 2007-04-02 | 2010-05-18 | Parkinson's Institute | Methods and compositions for reduction of side effects of therapeutic treatments |
US10512597B2 (en) * | 2007-09-06 | 2019-12-24 | Colgate-Palmolive Company | Controlled surface gelling of mucoadhesive polymers on oral mucosa |
SI2211896T1 (en) | 2007-11-13 | 2018-04-30 | Meritage Pharma, Inc. | Compositions for the treatment of gastrointestinal inflammation |
US20100216754A1 (en) * | 2007-11-13 | 2010-08-26 | Meritage Pharma, Inc. | Compositions for the treatment of inflammation of the gastrointestinal tract |
US20090123551A1 (en) * | 2007-11-13 | 2009-05-14 | Meritage Pharma, Inc. | Gastrointestinal delivery systems |
US20090143343A1 (en) * | 2007-11-13 | 2009-06-04 | Meritage Pharma, Inc. | Compositions for the treatment of inflammation of the gastrointestinal tract |
US20090264392A1 (en) * | 2008-04-21 | 2009-10-22 | Meritage Pharma, Inc. | Treating eosinophilic esophagitis |
CN102170875A (en) * | 2008-10-06 | 2011-08-31 | Wm.雷格利Jr.公司 | Chewing gum containing low dose amounts of water soluble vitamins |
EP2385769A4 (en) * | 2008-12-15 | 2014-08-20 | Valeant Pharmaceuticals Luxembourg S R L | Rapidly dissolving vitamin formulation and methods of using the same |
MY173823A (en) * | 2009-01-23 | 2020-02-24 | Hanmi Science Co Ltd | Solid pharmaceutical composition comprising amlodipine and losartan and process for producing same |
US20100278913A1 (en) * | 2009-04-30 | 2010-11-04 | Sancilio & Company | Chewable tablet |
US20110223312A1 (en) * | 2009-11-30 | 2011-09-15 | Daniel Perlman | Triglyceride-encapsulated phytosterol microparticles dispersed in beverages |
CN102970992B (en) | 2010-05-12 | 2016-07-06 | 莱姆派克斯制药公司 | tetracycline compositions |
EP2729148A4 (en) | 2011-07-06 | 2015-04-22 | Parkinson S Inst | Compositions and methods for treatment of symptoms in parkinson's disease patients |
US20130071476A1 (en) * | 2011-08-19 | 2013-03-21 | Subraman Rao Cherukuri | Rapid Melt Controlled Release Taste-Masked Compositions |
US8460738B1 (en) | 2012-05-04 | 2013-06-11 | Brandeis University | Liquid crystalline phytosterol-glycerine complex for enhanced bioavailability and water dispersal |
DE102013004263A1 (en) * | 2013-03-13 | 2014-09-18 | Martin Lipsdorf | Fast-dissolving oral dosage form and method of making the same |
WO2016123406A1 (en) | 2015-01-28 | 2016-08-04 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
CA2977814A1 (en) | 2015-03-12 | 2016-09-15 | Chrono Therapeutics Inc. | Craving input and support system |
US10292977B2 (en) | 2016-04-11 | 2019-05-21 | Neurocea, LLC | Compositions and methods for treatment related to fall and fall frequency in neurodegenerative diseases |
US10143687B2 (en) | 2016-04-11 | 2018-12-04 | Neurocea, LLC | Compositions and methods for treatment related to fall and fall frequency in neurodegenerative diseases |
JP2020503950A (en) | 2017-01-06 | 2020-02-06 | クロノ セラピューティクス インコーポレイテッドChrono Therapeutics Inc. | Device and method for transdermal drug delivery |
EP3568124A1 (en) | 2017-01-11 | 2019-11-20 | Ferring B.V. | A fast disintegrating pharmaceutical composition |
WO2019232077A1 (en) | 2018-05-29 | 2019-12-05 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
WO2023011660A1 (en) * | 2021-08-06 | 2023-02-09 | Sansure Biotech Inc. | Compositions for liquefying a viscous biological sample, combination products, liquefying agents, and kits thereof, and methods and application thereof |
Citations (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4327076A (en) * | 1980-11-17 | 1982-04-27 | Life Savers, Inc. | Compressed chewable antacid tablet and method for forming same |
US4327077A (en) * | 1981-05-29 | 1982-04-27 | Life Savers, Inc. | Compressed chewable antacid tablet and method for forming same |
US4446135A (en) * | 1982-06-07 | 1984-05-01 | Sterling Drug Inc. | Chewable antacid tablets |
US4609543A (en) * | 1983-11-14 | 1986-09-02 | Nabisco Brands, Inc. | Soft homogeneous antacid tablet |
US4684534A (en) * | 1985-02-19 | 1987-08-04 | Dynagram Corporation Of America | Quick-liquifying, chewable tablet |
US4686212A (en) * | 1985-08-13 | 1987-08-11 | Pharmacontrol Corp. | Stable sodium aspirin tablet compositions |
US4832956A (en) * | 1985-09-25 | 1989-05-23 | Gerhard Gergely | Disintegrating tablet and process for its preparation |
US4937076A (en) * | 1984-08-10 | 1990-06-26 | Combe Incorporated | Chewable aspirin and buffering material tablet and method for producing same |
US5204116A (en) * | 1991-05-01 | 1993-04-20 | Alza Corporation | Dosage form providing immediate therapy followed by prolonged therapy |
US5320848A (en) * | 1991-05-28 | 1994-06-14 | Affinity Biotech, Inc. | Chewable drug-delivery composition |
US5429836A (en) * | 1991-10-25 | 1995-07-04 | Fuisz Technologies Ltd. | Saccharide-based matrix |
US5614199A (en) * | 1992-07-08 | 1997-03-25 | Lek, Tovarna Farmacevtskih In Kemicnih Izdelkov, D.D., Ljubljana | Inclusion complexes of clavulanic acid and of alkali salts thereof with hydrophilic and hydrophobic β-cyclodextrin derivatives, a process for the preparation thereof and the use thereof |
US5690959A (en) * | 1993-05-29 | 1997-11-25 | Smithkline Beecham Corporation | Pharmaceutical thermal infusion process |
US5753255A (en) * | 1997-02-11 | 1998-05-19 | Chavkin; Leonard | Chewable molded tablet containing medicinally active substances |
US5837285A (en) * | 1992-02-18 | 1998-11-17 | Nakamichi; Kouichi | Fast soluble tablet |
US5840334A (en) * | 1997-08-20 | 1998-11-24 | Fuisz Technologies Ltd. | Self-binding shearform compositions |
US5910322A (en) * | 1994-08-17 | 1999-06-08 | Smithkline Beecham P.L.C. | Delayed release pharmaceutical formulation containing amoxycillin and potassium clavulanate |
US5912012A (en) * | 1997-09-06 | 1999-06-15 | Carlin; Edward J. | Effervescent systems with simplified packaging requirements |
US5989583A (en) * | 1996-04-02 | 1999-11-23 | Pharmos Ltd. | Solid lipid compositions of lipophilic compounds for enhanced oral bioavailability |
US6024981A (en) * | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
US6051255A (en) * | 1994-04-23 | 2000-04-18 | Smithkline Beecham Plc | Polymer coated tablet comprising amoxycillin and clavulanate |
US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US6375982B1 (en) * | 2000-07-05 | 2002-04-23 | Capricorn Pharma, Inc. | Rapid-melt semi-solid compositions, methods of making same and method of using same |
US6419954B1 (en) * | 2000-05-19 | 2002-07-16 | Yamanouchi Pharmaceutical Co., Ltd. | Tablets and methods for modified release of hydrophilic and other active agents |
US6645988B2 (en) * | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
US6696085B2 (en) * | 1998-07-20 | 2004-02-24 | Antares Pharma Ipl Ag | Use of an acrylic type polymer as disintegrating agent |
US6719996B2 (en) * | 2000-12-14 | 2004-04-13 | Hoffmann-La Roche Inc. | Galenic composition for low bioavailability medicaments |
US20040220276A1 (en) * | 2001-07-26 | 2004-11-04 | Gerard Cousin | Coated granules of allylamine-or benzylamine-anti-mycotics |
US20040247677A1 (en) * | 2003-06-06 | 2004-12-09 | Pascal Oury | Multilayer orodispersible tablet |
US20050196438A1 (en) * | 2004-03-08 | 2005-09-08 | Pharmaceutical Industry Technology And Development Center | Fast dissolving tablet and method of preparing the same |
US7122204B2 (en) * | 2000-02-24 | 2006-10-17 | Advancis Pharmaceutical Corporation | Antibiotic composition with inhibitor |
US7229641B2 (en) * | 2000-07-05 | 2007-06-12 | Capricorn Pharma, Inc. | Rapid-melt compositions methods of making same and methods of using same |
US7282217B1 (en) * | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
US20080014268A1 (en) * | 2006-06-26 | 2008-01-17 | Capricorn Pharma Inc. | Orally disintegrating layered compositions |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4786502A (en) | 1986-10-06 | 1988-11-22 | The Procter & Gamble Company | Palatable solid pharmaceutical compositions |
GB2195891A (en) | 1986-10-06 | 1988-04-20 | Procter & Gamble | Improving palatability of pharmaceutical chewable tablets |
US5419954A (en) * | 1993-02-04 | 1995-05-30 | The Alpha Corporation | Composition including a catalytic metal-polymer complex and a method of manufacturing a laminate preform or a laminate which is catalytically effective for subsequent electroless metallization thereof |
EP0667640A3 (en) * | 1994-01-14 | 1997-05-14 | Brush Wellman | Multilayer laminate product and process. |
US6024363A (en) * | 1996-09-30 | 2000-02-15 | Johnson, Jr.; Theodore C. | Gasket for use with an air brake hose coupling member |
US6735982B2 (en) * | 2001-07-12 | 2004-05-18 | Intel Corporation | Processing relatively thin glass sheets |
-
2001
- 2001-07-05 WO PCT/US2001/041272 patent/WO2002002081A1/en active Application Filing
- 2001-07-05 AU AU2001279284A patent/AU2001279284A1/en not_active Abandoned
-
2002
- 2002-08-01 US US10/208,877 patent/US7229641B2/en not_active Expired - Fee Related
-
2007
- 2007-06-12 US US11/818,212 patent/US20080020065A1/en not_active Abandoned
-
2009
- 2009-03-24 US US12/409,574 patent/US20090304824A1/en not_active Abandoned
Patent Citations (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4327076A (en) * | 1980-11-17 | 1982-04-27 | Life Savers, Inc. | Compressed chewable antacid tablet and method for forming same |
US4327077A (en) * | 1981-05-29 | 1982-04-27 | Life Savers, Inc. | Compressed chewable antacid tablet and method for forming same |
US4446135A (en) * | 1982-06-07 | 1984-05-01 | Sterling Drug Inc. | Chewable antacid tablets |
US4609543A (en) * | 1983-11-14 | 1986-09-02 | Nabisco Brands, Inc. | Soft homogeneous antacid tablet |
US4937076A (en) * | 1984-08-10 | 1990-06-26 | Combe Incorporated | Chewable aspirin and buffering material tablet and method for producing same |
US4684534A (en) * | 1985-02-19 | 1987-08-04 | Dynagram Corporation Of America | Quick-liquifying, chewable tablet |
US4686212A (en) * | 1985-08-13 | 1987-08-11 | Pharmacontrol Corp. | Stable sodium aspirin tablet compositions |
US4832956A (en) * | 1985-09-25 | 1989-05-23 | Gerhard Gergely | Disintegrating tablet and process for its preparation |
US5204116A (en) * | 1991-05-01 | 1993-04-20 | Alza Corporation | Dosage form providing immediate therapy followed by prolonged therapy |
US5320848A (en) * | 1991-05-28 | 1994-06-14 | Affinity Biotech, Inc. | Chewable drug-delivery composition |
US5429836A (en) * | 1991-10-25 | 1995-07-04 | Fuisz Technologies Ltd. | Saccharide-based matrix |
US5837285A (en) * | 1992-02-18 | 1998-11-17 | Nakamichi; Kouichi | Fast soluble tablet |
US5614199A (en) * | 1992-07-08 | 1997-03-25 | Lek, Tovarna Farmacevtskih In Kemicnih Izdelkov, D.D., Ljubljana | Inclusion complexes of clavulanic acid and of alkali salts thereof with hydrophilic and hydrophobic β-cyclodextrin derivatives, a process for the preparation thereof and the use thereof |
US5690959A (en) * | 1993-05-29 | 1997-11-25 | Smithkline Beecham Corporation | Pharmaceutical thermal infusion process |
US6051255A (en) * | 1994-04-23 | 2000-04-18 | Smithkline Beecham Plc | Polymer coated tablet comprising amoxycillin and clavulanate |
US5910322A (en) * | 1994-08-17 | 1999-06-08 | Smithkline Beecham P.L.C. | Delayed release pharmaceutical formulation containing amoxycillin and potassium clavulanate |
US6645988B2 (en) * | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
US5989583A (en) * | 1996-04-02 | 1999-11-23 | Pharmos Ltd. | Solid lipid compositions of lipophilic compounds for enhanced oral bioavailability |
US5753255A (en) * | 1997-02-11 | 1998-05-19 | Chavkin; Leonard | Chewable molded tablet containing medicinally active substances |
US6024981A (en) * | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
US5840334A (en) * | 1997-08-20 | 1998-11-24 | Fuisz Technologies Ltd. | Self-binding shearform compositions |
US5912012A (en) * | 1997-09-06 | 1999-06-15 | Carlin; Edward J. | Effervescent systems with simplified packaging requirements |
US6696085B2 (en) * | 1998-07-20 | 2004-02-24 | Antares Pharma Ipl Ag | Use of an acrylic type polymer as disintegrating agent |
US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US7122204B2 (en) * | 2000-02-24 | 2006-10-17 | Advancis Pharmaceutical Corporation | Antibiotic composition with inhibitor |
US6419954B1 (en) * | 2000-05-19 | 2002-07-16 | Yamanouchi Pharmaceutical Co., Ltd. | Tablets and methods for modified release of hydrophilic and other active agents |
US6375982B1 (en) * | 2000-07-05 | 2002-04-23 | Capricorn Pharma, Inc. | Rapid-melt semi-solid compositions, methods of making same and method of using same |
US6589556B2 (en) * | 2000-07-05 | 2003-07-08 | Capricorn Pharma, Inc. | Rapid-melt semi-solid compositions, methods of making same and methods of using same |
US7229641B2 (en) * | 2000-07-05 | 2007-06-12 | Capricorn Pharma, Inc. | Rapid-melt compositions methods of making same and methods of using same |
US6719996B2 (en) * | 2000-12-14 | 2004-04-13 | Hoffmann-La Roche Inc. | Galenic composition for low bioavailability medicaments |
US20040220276A1 (en) * | 2001-07-26 | 2004-11-04 | Gerard Cousin | Coated granules of allylamine-or benzylamine-anti-mycotics |
US20040247677A1 (en) * | 2003-06-06 | 2004-12-09 | Pascal Oury | Multilayer orodispersible tablet |
US7282217B1 (en) * | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
US7425341B1 (en) * | 2003-08-29 | 2008-09-16 | K.V. Pharmaceutical Company | Rapidly disintegrable tablets |
US20050196438A1 (en) * | 2004-03-08 | 2005-09-08 | Pharmaceutical Industry Technology And Development Center | Fast dissolving tablet and method of preparing the same |
US20080014268A1 (en) * | 2006-06-26 | 2008-01-17 | Capricorn Pharma Inc. | Orally disintegrating layered compositions |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080069889A1 (en) * | 2006-03-07 | 2008-03-20 | Cherukuri S R | Compressible resilient granules and formulations prepared therefrom |
US20070243248A1 (en) * | 2006-04-14 | 2007-10-18 | Cherukuri S Rao | Rapidly disintegrating solid oral dosage form of liquid dispersions |
US20070259040A1 (en) * | 2006-05-01 | 2007-11-08 | Cherukuri S R | Novel triptan formulations and methods for making them |
US20080081072A1 (en) * | 2006-09-30 | 2008-04-03 | Cherukuri S R | Resin-complex granulation for water-soluble drugs and associated methods |
CN111991440A (en) * | 2020-08-24 | 2020-11-27 | 常州工学院 | Method for extracting flavonoid compounds in cinnamomum camphora by polymer aqueous two-phase extraction |
Also Published As
Publication number | Publication date |
---|---|
US20020187188A1 (en) | 2002-12-12 |
WO2002002081A1 (en) | 2002-01-10 |
US20080020065A1 (en) | 2008-01-24 |
AU2001279284A1 (en) | 2002-01-14 |
US7229641B2 (en) | 2007-06-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7229641B2 (en) | Rapid-melt compositions methods of making same and methods of using same | |
US6589556B2 (en) | Rapid-melt semi-solid compositions, methods of making same and methods of using same | |
US20100010101A1 (en) | Rapid-Melt Compositions and Methods of Making Same | |
US7678387B2 (en) | Drug delivery systems | |
US20130022675A1 (en) | Drug delivery system | |
KR900007468B1 (en) | Confectionery delivery system for actives | |
US20020044962A1 (en) | Encapsulation products for controlled or extended release | |
EP0950402B1 (en) | Chewable pharmaceutical composition with gelatin matrix | |
AU2001254826B2 (en) | Effervescent granules and methods for their preparation | |
CN110944640A (en) | Pectin adhesive compositions and methods of making and using same | |
JP2003506399A (en) | Means for producing bulking agents with structural integrity | |
SK74496A3 (en) | Organoleptically acceptable oral pharmaceutical compositions | |
AU711853B2 (en) | Oral formulations of S(+)-etodolac | |
US20070059367A1 (en) | Drug Delivery System and Associated Methods | |
US5686107A (en) | Chewable pharmaceutical tablets | |
WO2007086457A1 (en) | Quickly disintegrating tablet produced by direct dry-tabletting | |
PL209144B1 (en) | Solid orally-dispersible pharmaceutical formulation | |
Makwana et al. | Chewing gum: A modern approach to oral mucosal drug delivery | |
US20100196466A1 (en) | Drug delivery system | |
JP2023525277A (en) | Mouthwash for Oral Care Benefits | |
JP5902677B2 (en) | Orally disintegrating tablets of erythritol and isomalt | |
JP7303211B2 (en) | solid pharmaceutical tablet | |
WO2010067151A1 (en) | Quick disintegrating taste masked composition | |
WO2000009171A1 (en) | Products containing unpleasant tasting bio-affecting agents and methods of making them | |
WO2002092058A1 (en) | Rapidly disintegratable solid preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: CAPRICORN PHARMA, INC., MARYLAND Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CHERUKURI, S. RAO;REEL/FRAME:022771/0744 Effective date: 20090522 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |