CA2282906A1 - Stable complexes of poorly soluble compounds - Google Patents
Stable complexes of poorly soluble compounds Download PDFInfo
- Publication number
- CA2282906A1 CA2282906A1 CA002282906A CA2282906A CA2282906A1 CA 2282906 A1 CA2282906 A1 CA 2282906A1 CA 002282906 A CA002282906 A CA 002282906A CA 2282906 A CA2282906 A CA 2282906A CA 2282906 A1 CA2282906 A1 CA 2282906A1
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- CA
- Canada
- Prior art keywords
- compound
- polymer
- ionic polymer
- insoluble
- therapeutically active
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Abstract
Stable water-insoluble complexes of poorly soluble compounds molecularly dispersed in water-insoluble ionic polymers are disclosed. Useful insoluble ionic polymers have a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°. The compounds are microprecipitated in the ionic polymers in amorphous form. The complexes according to the present invention significantly increase the bioavailability of poorly soluble therapeutically active compounds.
Claims (46)
1. A pharmaceutical composition comprising a water-insoluble complex of a therapeutically active, stable amorphous compound and a water-insoluble ionic polymer that has a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°C, and a carrier.
2. The pharmaceutical composition of claim 1 wherein the therapeutically active compound is a compound that is poorly soluble when in crystalline form.
3. The pharmaceutical composition of claim 2 wherein the poorly soluble therapeutically active compound in its crystalline form has a solubility of less than 1 mg/mL in aqueous solution.
4. The pharmaceutical composition of claim 1 wherein the ionic polymer is a cationic polymer.
5. The pharmaceutical composition of claim 4 wherein the cationic polymer is a copolymer of dimethylaminoethylmethacrylate and neutral methacrylic ester.
6. The pharmaceutical composition of claim 5 wherein the cationic polymer is Eudragit E R.
7. The pharmaceutical composition of claim 1 wherein the ionic polymer is an anionic polymer.
8. The pharmaceutical composition of claim 7 wherein the anionic polymer is a copolymer of methacrylic acid and ethyl acrylate or methacrylic acid and methyl methacrylate.
9. The pharmaceutical composition of claim 8 wherein the anionic polymer is selected from the group consisting of Eudragit L 100-55R , Eudragit L-100R
and Eudragit S-100R.
and Eudragit S-100R.
10. The pharmaceutical composition of claim 7 wherein the anionic polymer is selected from the group consisting of polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, cellulose acetate terphthalate, polycyanoacrylate and hydroxypropyl methyl cellulose acetyl succinate, carboxy methyl cellulose, and low substituted hydroxypropylcellulose.
11. The pharmaceutical composition of claim 1 wherein the solubility of the ionic polymer is pH dependent.
12. The pharmaceutical composition of claim 11 wherein the ionic polymer is insoluble at pH above about 4.
13. The pharmaceutical composition of claim 1 wherein the ionic polymer and the therapeutically active compound in its crystalline form are both relatively insoluble above pH of about 4.
14. The pharmaceutical composition of claim 11 wherein the ionic polymer is insoluble at pH below about 4.
15. The pharmaceutical composition of claim 1 wherein the ionic polymer and the therapeutically active compound in its crystalline form are both relatively insoluble at pH below about 4.
16. The pharmaceutical composition of claim 1 wherein the therapeutically active compound is selected from the group consisting of Compounds I, II, III, IV, V, VI, VII and VIII.
17. A pharmaceutical composition comprising a water-insoluble complex of Compound I in stable amorphous form and a water-insoluble ionic polymer that has a molecular weight greater than about 80,000 D and a glass transition temperature equal to or greater than about 50°C, and a carrier.
18. The pharmaceutical composition of claim 1 wherein the ionic polymer is.
present in the water-insoluble complex at not less than about 20%, by weight.
present in the water-insoluble complex at not less than about 20%, by weight.
19. The pharmaceutical composition of claim 18 wherein the therapeutically active compound is present in the water-insoluble complex at about 0.1% to about 80%, by weight of said complex.
20. The pharmaceutical composition of claim 19 wherein the therapeutically active compound is present in the water-insoluble complex at about 30% to about 70%, by weight of said complex.
21. The pharmaceutical composition of claim 20 wherein the ionic polymer is present in the water-insoluble complex at about 50%, by weight, and the therapeutically active compound is present at about 50%, by weight of said complex.
22. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable, amorphous therapeutically active compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound and ionic polymer in a suitable solvent;
(b) contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble thereby microprecipitation the therapeutically active compound and ionic polymer as a compound/polymer complex;
(c) preparing a pharmaceutical formulation that includes the compound/ polymer complex of step (b) above.
(a) dissolving the therapeutically active compound and ionic polymer in a suitable solvent;
(b) contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble thereby microprecipitation the therapeutically active compound and ionic polymer as a compound/polymer complex;
(c) preparing a pharmaceutical formulation that includes the compound/ polymer complex of step (b) above.
23. The method of claim 22, wherein in step (a), the therapeutically active compound and the ionic polymer are dissolved in a solvent selected from the group consisting of ethyl alcohol, methyl alcohol, dimethylsulfoxide, dimethylacetamide, dimethyl formamide, N-methylpyrrolidone, Transcutol R (diethylene glycol monoethyl ether, Gattefosse), glycofural, propylene carbonate, tetrahydrofuran, polyethylene glycol and propylene glycol.
24. The method in claim 22 wherein in step (b), microprecipitation is carried out by removing the solvent by spray drying or lyophilizing.
25. The method of claim 22 wherein in step (a), the insoluble therapeutically active and the ionic compound polymer are dissolved by adjusting the pH.
26. The method of claim 22 wherein after step (b), residual solvent is removed.
27. The method of claim 26 wherein the residual solvent is removed by washing the compound/polymer complex.
28. The method of claim 26 wherein the residual solvent is removed by evaporation or drying.
29. The method of claim 28 wherein the residual solvent is removed by spray drying.
30. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable, amorphous therapeutically active compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound, in its crystalline form, and ionic polymer in an organic solvent;
(b) contacting the product of step (a) with an aqueous solution at a pH at which the ionic polymer and the therapeutically active compound will precipitate as a compound/polymer matrix;
(c) washing the compound/polymer matrix;
(d) drying the compound/polymer matrix; and (e) preparing a pharmaceutical formulation that incorporates the washed and dried compound/polymer matrix of step (d) above.
(a) dissolving the therapeutically active compound, in its crystalline form, and ionic polymer in an organic solvent;
(b) contacting the product of step (a) with an aqueous solution at a pH at which the ionic polymer and the therapeutically active compound will precipitate as a compound/polymer matrix;
(c) washing the compound/polymer matrix;
(d) drying the compound/polymer matrix; and (e) preparing a pharmaceutical formulation that incorporates the washed and dried compound/polymer matrix of step (d) above.
31. The method of claim 30 wherein the therapeutically active compound that is incorporated in the compound/polymer matrix is predominantly in amorphous form.
32. The method of claim 31 wherein the ionic polymer is selected from the group consisting of Eudragit R E100, Eudragit R L100, Eudragit R L100-55 and Eudragit R S100.
33. A method for preparing a water-insoluble complex of a stable amorphous compound and an ionic polymer comprising:
(a) melting together the therapeutically active compound and the ionic polymer; and (b) cooling the mixture resulting from step (a).
(a) melting together the therapeutically active compound and the ionic polymer; and (b) cooling the mixture resulting from step (a).
34. A method for preparing a pharmaceutical formulation comprising a water-insoluble complex of a stable amorphous compound and an ionic polymer comprising:
(a) dissolving the therapeutically active compound and the ionic polymer in a supercritical fluid;
(b) removing the supercritical fluid resulting in the microprecipitation of the therapeutically active compound in the polymer matrix; and (c) preparing a pharmaceutically formulation that includes the product of step (b) above.
(a) dissolving the therapeutically active compound and the ionic polymer in a supercritical fluid;
(b) removing the supercritical fluid resulting in the microprecipitation of the therapeutically active compound in the polymer matrix; and (c) preparing a pharmaceutically formulation that includes the product of step (b) above.
35. The method of claim 34 wherein the supercritical fluid used in step (a) is selected from the group consisting of liquid nitrogen and liquid carbon dioxide.
36. The method of claim 34 wherein removal of the supercritical fluid in step (b) is accomplished by evaporation.
37. The method of claim 22, 30, 33, 34 or 35 wherein the therapeutically active compound is selected from the group consisting of Compounds I, II, III, IV, V, VI, VII and VIII.
38. A stable, water-insoluble complex prepared by (a) dissolving Compound I and a water-insoluble ionic polymer having a molecular weight greater than 80,000D and a glass transition temperature equal to or greater than 50°C in a suitable solvent; and (b) co-precipitating Compound I and the ionic polymer as a compound/polymer complex.
39. The complex of claim 38 wherein precipitation in step (b) in effected by contacting the solution of step (a) with an aqueous solution at a pH in which the ionic polymer is poorly soluble.
40. A water-insoluble complex comprising a stable, amorphous compound and a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
41. The complex of claim 40 wherein the amorphous compound is poorly soluble in crystalline form.
42. A water-insoluble complex comprising Compound I in stable amorphous form and a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
43. A method for stabilizing an amorphous compound comprising molecularly dispersing the compound in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
44. A method for converting a poorly soluble, crystalline compound to a stable amorphous form of said compound comprising molecularly dispersing said compound in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
45. A therapeutically active compound in stable amorphous form molecularly dispersed in a water-insoluble ionic polymer that has a molecular weight greater than 80,000 D and a glass transition temperature equal to or greater than 50°C.
46. The invention as herein before described.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10133698P | 1998-09-22 | 1998-09-22 | |
| US60/101,336 | 1998-09-22 | ||
| US13653199P | 1999-05-28 | 1999-05-28 | |
| US60/136,531 | 1999-05-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2282906A1 true CA2282906A1 (en) | 2000-03-22 |
| CA2282906C CA2282906C (en) | 2010-07-20 |
Family
ID=26798138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2282906A Expired - Lifetime CA2282906C (en) | 1998-09-22 | 1999-09-20 | Stable complexes of poorly soluble compounds |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US6350786B1 (en) |
| EP (1) | EP0988863B2 (en) |
| JP (5) | JP2000095708A (en) |
| KR (1) | KR100362019B1 (en) |
| CN (1) | CN1201821C (en) |
| AR (2) | AR022096A1 (en) |
| AT (1) | ATE265232T1 (en) |
| AU (1) | AU770745B2 (en) |
| BR (1) | BR9904283A (en) |
| CA (1) | CA2282906C (en) |
| CO (1) | CO5140077A1 (en) |
| CZ (1) | CZ300215B6 (en) |
| DE (1) | DE69916733T3 (en) |
| DK (1) | DK0988863T4 (en) |
| ES (1) | ES2218918T5 (en) |
| HK (1) | HK1026632A1 (en) |
| HR (1) | HRP990287B1 (en) |
| HU (1) | HU228341B1 (en) |
| ID (1) | ID24034A (en) |
| IL (1) | IL131957A (en) |
| MA (1) | MA26692A1 (en) |
| MY (1) | MY124377A (en) |
| NO (1) | NO326928B1 (en) |
| NZ (1) | NZ337884A (en) |
| PE (1) | PE20001049A1 (en) |
| PL (1) | PL202757B1 (en) |
| PT (1) | PT988863E (en) |
| RS (1) | RS50193B (en) |
| RU (1) | RU2240827C2 (en) |
| SG (1) | SG97131A1 (en) |
| SI (1) | SI0988863T2 (en) |
| TR (1) | TR199902324A3 (en) |
| TW (1) | TWI234465B (en) |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2307482T3 (en) | 1999-02-10 | 2008-12-01 | Pfizer Products Inc. | SOLID PHARMACEUTICAL DISPERSIONS. |
| US6440959B1 (en) | 1999-04-21 | 2002-08-27 | Hoffman-La Roche Inc. | Pyrazolobenzodiazepines |
| CO5210860A1 (en) * | 1999-10-01 | 2002-10-30 | Hoffmann La Roche | NEW DERIVATIVES OF PIRIMIDINA-2,4,6-TRIONA |
| US6313143B1 (en) * | 1999-12-16 | 2001-11-06 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| AU5543801A (en) * | 2000-05-16 | 2001-11-26 | Ortho Mcneil Pharm Inc | Process for coating medical devices using super-critical carbon dioxide |
| US6482847B2 (en) * | 2000-10-03 | 2002-11-19 | Hoffmann-La Roche Inc. | Amorphous form of cell cycle inhibitor having improved solubility and bioavailability |
| US6469179B1 (en) | 2000-10-03 | 2002-10-22 | Hoffmann-La Roche Inc. | Amorphous form of cell cycle inhibitor having improved solubility and bioavailability |
| US20050048126A1 (en) | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
| US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
| US8067032B2 (en) | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
| US6548531B2 (en) | 2001-02-09 | 2003-04-15 | Hoffmann-La Roche Inc. | Method for cancer therapy |
| US6716845B2 (en) | 2001-03-30 | 2004-04-06 | Hoffmann-La Roche Inc. | Barbituric acid derivatives |
| AU2002310567B2 (en) * | 2001-05-30 | 2005-10-20 | Csir | Method of encapsulating an active substance |
| US20030044514A1 (en) * | 2001-06-13 | 2003-03-06 | Richard Robert E. | Using supercritical fluids to infuse therapeutic on a medical device |
| WO2002102373A1 (en) * | 2001-06-15 | 2002-12-27 | F. Hoffmann-La Roche Ag | Method for administration of cancer therapeutic |
| JP2004534812A (en) | 2001-06-22 | 2004-11-18 | ファイザー・プロダクツ・インク | Pharmaceutical composition of dispersion of drug and neutral polymer |
| MXPA03011933A (en) | 2001-06-22 | 2004-03-26 | Pfizer Prod Inc | Pharmaceutical compositions comprising low-solubility and/or acid-sensitive drugs and neutralized acidic polymers. |
| US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
| CA2461349C (en) | 2001-09-26 | 2011-11-29 | Baxter International Inc. | Preparation of submicron sized nanoparticles via dispersion and solvent or liquid phase removal |
| US20030139373A1 (en) * | 2001-11-20 | 2003-07-24 | Breimer Lars Holger | Method for cancer therapy |
| MXPA04007433A (en) | 2002-02-01 | 2004-10-11 | Pfizer Prod Inc | Method for making homogeneous spray-dried solid amorphous drug dispersions utilizing modified spray-drying apparatus. |
| DE60329188D1 (en) | 2002-08-12 | 2009-10-22 | Bend Res Inc | DRUG PREPARATIONS CONSISTING OF MEDICINAL PRODUCTS IN HALF-ORIENTED FORM AND POLYMERS |
| DE10351087A1 (en) * | 2003-10-31 | 2005-05-25 | Bayer Technology Services Gmbh | Solid active ingredient formulation |
| WO2005046697A1 (en) * | 2003-11-14 | 2005-05-26 | Ajinomoto Co., Inc. | Sustained-release phenylalanine derivative preparation for oral administration |
| PL1683524T3 (en) * | 2003-11-14 | 2011-06-30 | Ea Pharma Co Ltd | Solid dispersion or medicinal solid dispersion preparation of phenylalanine derivative |
| JP4787240B2 (en) * | 2004-04-01 | 2011-10-05 | ユニベルシテ・ド・リエージュ | Cyclodextrin inclusion complex of pyrimidine-2,4,6-trione |
| AR049915A1 (en) * | 2004-06-14 | 2006-09-13 | Anacor Pharmaceuticals Inc | COMPOUNDS WITH BORO CONTENT AND METHODS OF USE OF THE SAME |
| WO2006062980A2 (en) * | 2004-12-07 | 2006-06-15 | Nektar Therapeutics | Stable non-crystalline formulation comprising tiagabine |
| CN101115469A (en) * | 2004-12-28 | 2008-01-30 | 卫材R&D管理有限公司 | Quick disintegration tablet and method of producing the same |
| EP1848430B1 (en) * | 2004-12-31 | 2017-08-02 | Dr. Reddy's Laboratories Ltd. | Novel benzylamine derivatives as cetp inhibitors |
| US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| EP1690528A1 (en) * | 2005-02-11 | 2006-08-16 | Abbott GmbH & Co. KG | Process for the preparation of dosage forms comprising a solid dispersion of a microcrystalline active agent |
| JP2008540629A (en) * | 2005-05-19 | 2008-11-20 | ファイザー・インク | Pharmaceutical composition comprising amorphous VEGF-R inhibitor |
| EP1767194A1 (en) * | 2005-06-09 | 2007-03-28 | Helm AG | Process for the preparation of adsorbates of drospirenone |
| CN102603581B (en) * | 2005-06-22 | 2015-06-24 | 普莱希科公司 | Pyrrolo[2,3-b] pyridine derivatives as protein kinase inhibitors |
| US20080031944A1 (en) * | 2006-08-04 | 2008-02-07 | Cima Labs Inc. | Stabilization of lorazepam |
| TW200815033A (en) * | 2006-08-10 | 2008-04-01 | Cipla Ltd | Antiretroviral solid oral composition |
| US20080107725A1 (en) * | 2006-10-13 | 2008-05-08 | Albano Antonio A | Pharmaceutical Solid Dosage Forms Comprising Amorphous Compounds Micro-Embedded in Ionic Water-Insoluble Polymers |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| PE20081581A1 (en) * | 2006-12-21 | 2008-11-12 | Plexxikon Inc | PIRROLO [2,3-b] PYRIDINES COMPOUNDS AS KINASE MODULATORS |
| WO2008079909A1 (en) * | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| EP2127677A4 (en) * | 2006-12-27 | 2012-05-02 | Astellas Pharma Inc | Aminoalkylmethacrylate copolymer e for maintaining solubility of poorly water-soluble drug |
| JP2010526848A (en) * | 2007-05-11 | 2010-08-05 | エフ．ホフマン−ラ ロシュ アーゲー | Pharmaceutical composition for poorly soluble drugs |
| US8426467B2 (en) | 2007-05-22 | 2013-04-23 | Baxter International Inc. | Colored esmolol concentrate |
| US8722736B2 (en) | 2007-05-22 | 2014-05-13 | Baxter International Inc. | Multi-dose concentrate esmolol with benzyl alcohol |
| EP1997479A1 (en) * | 2007-05-31 | 2008-12-03 | Helm AG | Stabilized amorphous candesartan cilexetil compositions for oral administration |
| US20100190777A1 (en) | 2007-07-17 | 2010-07-29 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| AU2008312321A1 (en) * | 2007-10-19 | 2009-04-23 | Purdue Research Foundation | Solid formulations of crystalline compounds |
| US8632805B2 (en) * | 2008-06-20 | 2014-01-21 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations, method of manufacture, and use thereof |
| US7794750B2 (en) * | 2008-06-20 | 2010-09-14 | Mutual Pharmaceutical Company, Inc. | Controlled-release formulations, method of manufacture, and use thereof |
| US20100099696A1 (en) * | 2008-10-16 | 2010-04-22 | Anthony Edward Soscia | Tamper resistant oral dosage forms containing an embolizing agent |
| KR20100073454A (en) * | 2008-12-23 | 2010-07-01 | 국립암센터 | Novel pyrazolodiazepine compound as an transglutaminase inhibitor, the preparation method thereof and a composition containing the same |
| CR20170089A (en) * | 2009-04-03 | 2017-07-17 | Plexxikon Inc | PROPANE-ACID COMPOSITIONS-1 - SULFONIC {3- [5- (4-CHLORINE-PHENYL) -1H-PIRROLO [2,3-B] PIRIDINA-3-CARBONIL] -2,4-DIFLUORO-PHENIL} -AMIDA AND THE USE OF THE SAME |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| NZ599866A (en) | 2009-11-06 | 2014-09-26 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| CN103153306A (en) * | 2010-05-31 | 2013-06-12 | 安斯泰来制药有限公司 | Solid dispersion comprising triazole compound |
| MA34948B1 (en) | 2011-02-07 | 2014-03-01 | Plexxikon Inc | COMPOUNDS AND METHODS FOR MODULATING KINASE, AND INDICATIONS THEREOF |
| KR20140006879A (en) | 2011-02-17 | 2014-01-16 | 에프. 호프만-라 로슈 아게 | A process for controlled crystallization of an active pharmaceutical ingredient from supercooled liquid state by hot melt extrusion |
| TWI558702B (en) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | Solid forms of a pharmaceutically active substance |
| MX2014001849A (en) | 2011-08-18 | 2014-10-24 | Reddys Lab Ltd Dr | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (cetp) inhibitors. |
| WO2013037396A1 (en) * | 2011-09-12 | 2013-03-21 | Bioneer A/S | Solution of polymer in api for a solid dosage form |
| CN103958511A (en) | 2011-09-27 | 2014-07-30 | 雷迪博士实验室有限公司 | 5 - benzylaminomethyl - 6 - aminopyrazolo [3, 4 -b] pyridine derivatives as cholesteryl ester -transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis |
| SG11201401459YA (en) * | 2011-10-14 | 2014-07-30 | Array Biopharma Inc | Solid dispersions of a erb2 (her2) inhibitor |
| EP4252855A3 (en) | 2012-03-23 | 2023-11-15 | Array Biopharma, Inc. | Compounds for use in the treatment of brain metastases in a patient with erbb2+ breast cancer |
| US20140128431A1 (en) | 2012-04-03 | 2014-05-08 | Hoffmann-Laroche Inc. | Pharmaceutical composition with improved bioavailability, safety and tolerability |
| EP2649989B1 (en) | 2012-04-13 | 2017-10-18 | King Saud University | Method for preparing a solid dispersion, solid dispersion obtained thereby and use thereof |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| JO3339B1 (en) * | 2012-09-11 | 2019-03-13 | Shanghai Inst Pharmaceutical Ind | Stabilised amorphous form of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
| AU2013346501B2 (en) | 2012-11-19 | 2017-07-13 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions of CETP inhibitors |
| RU2015128794A (en) * | 2012-12-20 | 2017-01-25 | КАШИВ ФАРМА, ЭлЭлСи | COMPOSITION OF ORAL DECOMPOSABLE TABLETS, ENSURING INCREASED BIOAVAILABILITY |
| JP6192244B2 (en) | 2013-01-22 | 2017-09-06 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Pharmaceutical composition having improved bioavailability |
| TWI615157B (en) | 2013-02-06 | 2018-02-21 | 大塚製藥股份有限公司 | Solid dispersion comprising amorphous cilostazol |
| WO2015038376A1 (en) * | 2013-09-11 | 2015-03-19 | 3M Innovative Properties Company | Coating compositions, dental structures thereof and methods for generating contrast |
| EP3076951B1 (en) * | 2013-12-05 | 2020-09-30 | Celal Albayrak | Process for the production of drug formulations for oral administration |
| PT107846B (en) * | 2014-08-01 | 2019-03-22 | Hovione Farm S A | Production of Amorphous Solid Dispersion Nanoparticles by Controlled Co-Precipitation |
| CA2987517A1 (en) * | 2015-05-29 | 2016-12-08 | Sun Pharmaceutical Industries Limited | Oral pharmaceutical composition of isotretinoin |
| WO2018108079A1 (en) * | 2016-12-13 | 2018-06-21 | 南京药捷安康生物科技有限公司 | Multi-kinase inhibitor compound, and crystal form and use thereof |
| MA49059A (en) | 2017-04-28 | 2021-03-24 | Seagen Inc | TREATMENT OF POSITIVE HER2 CANCERS |
| KR102082775B1 (en) * | 2017-05-02 | 2020-02-28 | 주식회사 삼양바이오팜 | Formulation with enhanced water solubility and bioavailability |
| RU2725879C2 (en) * | 2018-07-26 | 2020-07-07 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Казанский Государственный медицинский университет" Министерства здравоохранения Российской Федерации | Interpolymer carrier for oral systems of controlled delivery of active pharmaceutical ingredients |
| CN113056457A (en) | 2018-12-03 | 2021-06-29 | H.隆德贝克有限公司 | 4- ((1R,3S) -6-chloro-3-phenyl-2, 3-dihydro-1H-inden-1-yl) -1,2, 2-trimethylpiperazine and 4- ((1R,3S) -6-chloro-3- (phenyl-d)5) -2, 3-dihydro-1H-inden-1-yl) -2, 2-dimethyl-1- (methyl-d3) Prodrugs of piperazine |
| EP4093379A1 (en) | 2020-01-24 | 2022-11-30 | Nanocopoeia LLC | Amorphous solid dispersions of dasatinib and uses thereof |
| JP2023513045A (en) | 2020-01-31 | 2023-03-30 | ナノコピーア リミテッド ライアビリティ カンパニー | Amorphous nilotinib microparticles and uses thereof |
| WO2021177320A1 (en) | 2020-03-03 | 2021-09-10 | デクセリアルズ株式会社 | Method for manufacturing image display device |
| WO2021222739A1 (en) | 2020-04-30 | 2021-11-04 | Nanocopoeia, Llc | Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51118816A (en) * | 1975-04-08 | 1976-10-19 | Meiji Seika Kaisha Ltd | A process for stabilizing non-crystalloidal solid |
| US4344934A (en) * | 1978-11-20 | 1982-08-17 | American Home Products Corporation | Therapeutic compositions with enhanced bioavailability |
| JPS62155263A (en) * | 1985-11-27 | 1987-07-10 | シンテツクス（ユ−・エス・エイ）インコ−ポレイテツド | Amorphous-benzimidazole derivative |
| CZ280738B6 (en) * | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituted pyrroles, their use for preparing medicaments and medicaments based thereon |
| JP2528706B2 (en) † | 1988-05-30 | 1996-08-28 | ゼリア新薬工業株式会社 | Pharmaceutical composition of dihydropyridine compound |
| USRE36736E (en) | 1989-02-06 | 2000-06-13 | Hoffman-La Roche Inc. | Substituted pyrroles |
| JPH0729926B2 (en) † | 1989-07-25 | 1995-04-05 | 大塚製薬株式会社 | Composition for easily absorbable preparations |
| US5399363A (en) | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
| EP0580860B2 (en) † | 1991-04-16 | 2004-12-15 | Nippon Shinyaku Company, Limited | Method of manufacturing solid dispersion |
| US5281420A (en) | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| TW493991B (en) | 1995-05-08 | 2002-07-11 | Novartis Ag | Pharmaceutical composition for oral administration of active agent having low water solubility and process for preparation of the same |
| GB9511220D0 (en) † | 1995-06-02 | 1995-07-26 | Glaxo Group Ltd | Solid dispersions |
| WO1997004782A1 (en) * | 1995-07-26 | 1997-02-13 | Kyowa Hakko Kogyo Co., Ltd. | Solid dispersion or solid dispersion preparation of xanthine derivatives |
| WO1997008950A1 (en) † | 1995-09-07 | 1997-03-13 | Fuisz Technologies, Ltd. | System for rendering substantially non-dissoluble bio-affecting agents bio-available |
| DE19548624A1 (en) | 1995-12-23 | 1997-06-26 | Boehringer Mannheim Gmbh | New barbituric acid derivatives, processes for their preparation and medicaments containing these compounds |
| JPH09208459A (en) * | 1996-02-07 | 1997-08-12 | Eisai Co Ltd | Preparation improved in solubility |
| NZ332234A (en) | 1996-03-12 | 2000-06-23 | Pg Txl Company Lp | Water soluble paclitaxel prodrugs formed by conjugating paclitaxel or docetaxel with a polyglutamic acid polymer and use for treating cancer |
| AU3483497A (en) * | 1996-06-28 | 1998-01-21 | Schering Corporation | Solid solution of an antifungal agent with enhanced bioavailability |
| PE91598A1 (en) | 1996-07-29 | 1998-12-24 | Hoffmann La Roche | SUBSTITUTED PYRROLES |
| US6229011B1 (en) | 1997-08-22 | 2001-05-08 | Hoffman-La Roche Inc. | N-aroylphenylalanine derivative VCAM-1 inhibitors |
| CN1127500C (en) | 1998-03-17 | 2003-11-12 | 弗·哈夫曼-拉罗切有限公司 | Substituted bisindolymaleimides for inhibition of cell proliferation |
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