CA1296628C - Ethanol fill formulation for softgels containing vitamins, dietary supplements and the like - Google Patents
Ethanol fill formulation for softgels containing vitamins, dietary supplements and the likeInfo
- Publication number
- CA1296628C CA1296628C CA000545611A CA545611A CA1296628C CA 1296628 C CA1296628 C CA 1296628C CA 000545611 A CA000545611 A CA 000545611A CA 545611 A CA545611 A CA 545611A CA 1296628 C CA1296628 C CA 1296628C
- Authority
- CA
- Canada
- Prior art keywords
- weight
- ethanol
- capsule
- fatty acids
- partial glycerides
- 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.)
- Expired - Lifetime
Links
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- General Preparation And Processing Of Foods (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Gelatin capsules of the type having an outer shell comprising gelatin and, optionally, a plasticizer, and a capsule filling, the filling containing at least one active substance and/or a dietetic agent or foodstuff as well as a solvent mixture, the solvent mixture containing about 5-50% by weight, preferably 10-30% by weight of ethanol and about 20-35% by weight, preferably 40-90% by weight of one or more of partial glycerides of fatty acids having from 6 to 18 carbon atoms.
The capsules are prepared by dissolving the active ingredients in the solvent mixture and filling the resulting mixture into the gelatin capsules.
Gelatin capsules of the type having an outer shell comprising gelatin and, optionally, a plasticizer, and a capsule filling, the filling containing at least one active substance and/or a dietetic agent or foodstuff as well as a solvent mixture, the solvent mixture containing about 5-50% by weight, preferably 10-30% by weight of ethanol and about 20-35% by weight, preferably 40-90% by weight of one or more of partial glycerides of fatty acids having from 6 to 18 carbon atoms.
The capsules are prepared by dissolving the active ingredients in the solvent mixture and filling the resulting mixture into the gelatin capsules.
Description
BA~KGI~OUND OF THE INVENTION
The present invention relates to gelatin capsules, both hard shell and soft shell or softgels, consisting of an envelope or shell comprising gelatin and optionally a plasticizer an~ a capsule filling containing at least one active substance and/or a dietetic agent or foodstuff as well as a solvent mixture, and to a process for preparing such capsules or softgels.
Soft gelatin capsules or softgels are predominantly used to contain liquids wherein the active ingredients are present in the dissolved or suspended state. The employed filling materials commonly include vegetable oils, animal oils and mineral oils, liquid hydrocarbons, ethereal oils and polyethylene glycol. Fats and waxes are also commonly used or added to the fill for increasing the consistency.
In recent years, there have also been developed processes for ;~ 15 filling liquids and pasty filling materials into two piece, telescoping hard gelatin capsules.
A particularly good bioavailability of pharmacologically active substances in the fill of the gelatin capsules is attained if the activc substance is successfully dissol~ed in a suitable solvent and the encapsulated solution is administered to a patient. However, such solvents may only include adjuvants which, on the one hand, are acceptable for application to the human organism and, on the other hand, do not impair the stability of the gelatin shell or envelope.
As discussed in DE-OS 33 07 353, there are known soft gelatin capsules or softgels containing, as a solvent, polyethylene glycol having an average alolecular weight of 600 as well as glycerol and/or 172-propylene glycol. These soft gelatin capsules have proven to be very valuable. f lowever, such polyethylene glycols are considerecl to be unsuitable solvents for some active substances. There are sensitive active materials such as, for example, sulfonamides or organic iodine compounds which are chemicaliy instable in polyethylene glycols.
Furthermore, a number of active substances have been known, for example, phenols or phenobarbital, for which a complex format;on occurs bctween the ethoxyl groups of the polyethylene glycols and the ~,~
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~2-active substances, which complexes cause a reduced bioavailability of the active substances to result. Eventually, there are also higher-dosed active materials, for example pentetrazole, which are not sufficiently soluble in polyethylene glycols i . .
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SUMMARY OF THE INVENT~ON
Thus, it is an object of the present invention to find solvents which are allowcd for human applications, which have good solvent power, and which do not produce undesired complexes by etboxyl 5 groups.
Ethanol has been known as being a good solvent for many pharmaceutically active substances and is frequently used for the preparation of dropping solutions. Contrary thereto, ethanol, thus far, could not be used for individual-dose gelatin capsules of sufficiently 10 high concentration, since concentrated ethanol is absorbed by the gelatin shell or envelope of the capsule, after preparation, and the gelatin shell becomes softened and deformed thereby; as a result, the capsules with the deformed gelatin shells are not acceptable in the trade.
According to what has been set forth by Czetsch-Lindenwald and Fahrig, Ar~neikapseln Aulendorf, 1962, p. 34, lower aliphatic alcohols may be filled into capsules only to about 5% by weight. In admixture with polyethylene glycols, in a specific recipe, according to DE-OS 35 09 741, a maximurn of 10% ethanol may be filled into gelatin capsules.
The present invention relates to gelatin capsules, both hard shell and soft shell or softgels, consisting of an envelope or shell comprising gelatin and optionally a plasticizer an~ a capsule filling containing at least one active substance and/or a dietetic agent or foodstuff as well as a solvent mixture, and to a process for preparing such capsules or softgels.
Soft gelatin capsules or softgels are predominantly used to contain liquids wherein the active ingredients are present in the dissolved or suspended state. The employed filling materials commonly include vegetable oils, animal oils and mineral oils, liquid hydrocarbons, ethereal oils and polyethylene glycol. Fats and waxes are also commonly used or added to the fill for increasing the consistency.
In recent years, there have also been developed processes for ;~ 15 filling liquids and pasty filling materials into two piece, telescoping hard gelatin capsules.
A particularly good bioavailability of pharmacologically active substances in the fill of the gelatin capsules is attained if the activc substance is successfully dissol~ed in a suitable solvent and the encapsulated solution is administered to a patient. However, such solvents may only include adjuvants which, on the one hand, are acceptable for application to the human organism and, on the other hand, do not impair the stability of the gelatin shell or envelope.
As discussed in DE-OS 33 07 353, there are known soft gelatin capsules or softgels containing, as a solvent, polyethylene glycol having an average alolecular weight of 600 as well as glycerol and/or 172-propylene glycol. These soft gelatin capsules have proven to be very valuable. f lowever, such polyethylene glycols are considerecl to be unsuitable solvents for some active substances. There are sensitive active materials such as, for example, sulfonamides or organic iodine compounds which are chemicaliy instable in polyethylene glycols.
Furthermore, a number of active substances have been known, for example, phenols or phenobarbital, for which a complex format;on occurs bctween the ethoxyl groups of the polyethylene glycols and the ~,~
'~
~l2~316~
~2-active substances, which complexes cause a reduced bioavailability of the active substances to result. Eventually, there are also higher-dosed active materials, for example pentetrazole, which are not sufficiently soluble in polyethylene glycols i . .
'.1~
!
:
, ..,`, ~ ,, .
'.'..:~
,. ~, . .
.
~2t~
SUMMARY OF THE INVENT~ON
Thus, it is an object of the present invention to find solvents which are allowcd for human applications, which have good solvent power, and which do not produce undesired complexes by etboxyl 5 groups.
Ethanol has been known as being a good solvent for many pharmaceutically active substances and is frequently used for the preparation of dropping solutions. Contrary thereto, ethanol, thus far, could not be used for individual-dose gelatin capsules of sufficiently 10 high concentration, since concentrated ethanol is absorbed by the gelatin shell or envelope of the capsule, after preparation, and the gelatin shell becomes softened and deformed thereby; as a result, the capsules with the deformed gelatin shells are not acceptable in the trade.
According to what has been set forth by Czetsch-Lindenwald and Fahrig, Ar~neikapseln Aulendorf, 1962, p. 34, lower aliphatic alcohols may be filled into capsules only to about 5% by weight. In admixture with polyethylene glycols, in a specific recipe, according to DE-OS 35 09 741, a maximurn of 10% ethanol may be filled into gelatin capsules.
2 0 However, the example therein only contains 7% by weight of ethanol.
This is confirmed by the European Patent Publication 0 170 623 which employs ethanol as a solvent for the active substance dihydro-(val)2-cyclosporine. Drink solutions contain l0 to 12% by weight of ethanol, whereas the soft gelatin capsules according to Example 2 contain only from 2 to 5% by weight.
lt has now surprisingly found that ethanol mixtures having an cthanol content in excess of 5% by weight7 up to about 50% by weight, can also be encapsulated without the addition of ethylene glycols to form stable preparations, if the solvent mixture contains at least 20%, up to about 95% by weight of partial glycerides of fatty acids having from 6 to 18 carbon atoms. A preferred range of ethanol is about l0-30% by weight and a preferred range of the partial glycerides of fatty acids is 40-90% by weight. Partial glycerides of fatty acids having , from 6 to 12 carbon atoms and/or ricinoleic acid are preferred to be employed.
. .
.
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, DETAILED DESCRIPTION OF
THE PREFERRED EMBODIMENT
The gelatin capsules which are the subject of the present invention comprise a gelatin shell which encloses a filling including an active substance, a dietetic agent or a foodstuff and a solvent mixture, the solvent mixture containing about 5-50% (preferably 10-30% by weight~ by weight of ethanol and about 20-95% by weight (preferably 40-90% by weight) of one or more partial glycerides of fatty acids having from 6-18 carbon atoms. The partial glycerides useful in the fill include monoglycerides o} diglycerides as well as mixtures thereof.
Suitable commercially available products inclucle, for example, glycerol ,~ monocaprylate (Imwitor * 308 of Dynamit Nobel), glycerol monodicaprylate (Imwitor 908), mixtures comprising glycerol mor odicaprylate and glycerol monodicaprate (Imwitor 742) and partial glycerldes of ricinoleic acid (Softigen~701 and Rilanit).
These partial glycerides are readily miscible with ethanol and even allow amounts of ethanol in excess of 10% to be employed in the solvent mixture without any deterioration of ~he stability of the gelatin envelope.
The gelatin capsules accordin8 to the present invention are prepared by dissolving the active substance in the mixture of ethanol and partial glycerides. As the ethanol-partial glyceride mixtures are miscible with lipophilic as well as hydrophilic components, various additives may be used if required, e.g. triglycerides of various fatty 2 5 acids or polyethylene glycols~ provided that they do not impair the stability of the active substances or of the gelatin shell of thc capsule.
The solutions according to the invention may be filled into hard gelatin capsules as well as into soft gelatin capsules. The envelope of soft gelatin capsules usually contain.s one or more plasticizers in addition to gelatin, such as glycerol, propylene glycol, sorbitol, or sorbitans. The shell may also contain colorants, preservatives, flavoring agents, sugar and other polyols.
When using soft gelatin capsules or softgels, the capsules are : 35 simultaneously formed and filled with a fill material using conventional . . ' ' : :~
', , : ' .
methods and procedures such as the rotary die process as discussed, for example, in the article of J.P. Stanley, "lI. Soft Gelatin Capsules,"
pp. 360-384, The Theorv and Practice of Industrial Pharmacv. Soft gel capsules or softgels conventionally comprise gelatin, a plasticizer, such as glycerin, or sorbitol and water. The gelatin shells also commonly contain a preservative, such as mixed parabens, for cxample, methyl or propyl parabens. The parabens are incorporated into the shell formulation in minor proportions as compared to the total weight of the shell formulation. Conventional soft gelatin capsules utilize gelatin having a bloom value of 150 to 200 although this value may be varied The fill material can vary over a wide range and may contain unit dosage amounts of pharmaceuticals, dietary supplements, vitamins and the like, often in liquid form. The capsules are commonly sized and shaped so as to be readily swallowable by a person, usually with the aid of water.
The invention is further illustrated by way of the following examples.
Exam~le I
A mixture of 300 mg of glycerol monocaprylate (]mwitor 30B) and 150 mg of ethanol was filled into soft gelatin capsules in a known manner according to the Rotary Die Process, and thc capsules wcre dried. Then the ethanol content of the capsule envelope was analyzcd, and an ethanol content of 4.5% was ~ound. The capsules were physically stable; capsule shape and capsule hardness were excellent.
Comr)arative Exam~e I
400 mg of ethanol were filled into soft gelatin capsules as in El~ample 1. After drying the ethanol content of the capsule envelope was 14.0%. The capsules were physically instable, deformed and shrinked due to the ethanol loss.
ComDarative ExarnDle 2 The mixture of 350 mg of medium-chain triglycerides (Miglyol 812) and 100 mg of ethanol were filled into soft gelatin capsules as in Example l. After drying the ethanol content of the capsule envelope ~6 Ei~
was 11.8%. The capsules were physically instable. They were soft and def ormed.
ExamDle 2 A mixture of 300 mg of glycerol mono/dioleate and I S0 mg of ethanol were filled into soft gelatin capsules as in Example 1. After drying the ethanol content of the capsule envelope was 7.8%. The capsule shape was satisfactory, but the capsules were softer than those of Example I because of the higher ethanol content in the envelope.
Exam~le 3 Hard gelatin capsules of size O having an average weight of 97 mg were filled with a mixture of 80% of glycerol monocaprylate (Imwitor 308) and 20% of ethanol and sealed with a gelatin filament. After one week the ethanol content of the capsule envelope was analyzed. The capsule envelopes contained 2% of ethanol, based on 97 mg of capsule 1 5 envelope.
Com~arative ExamDle 3 Hard gelatin capsules of size O as in Example 3 were filled with a mixture of 80% of medium-chain triglycerides ~Miglyol 812) and 20% of ethanol and sealed with a gelatin filament. After one week tlle ethanol content of the capsulç envelope was 11.1%, based on 97 mg of capsule envelope.
Examl)le 4 Pentetrazol100 mg Ethanol 20 mg Imwitor 742100 m~
Fill-in weight 220 mg Ethanol was added to the molten Imwitor 742, and the Pentctrazol was dissolved in the mixture. The finished solution was filled into soft gelatin capsules of size 4 minims. The dried capsules were 3 0 unobjectionable with respect to capsule hardness and capsule appearance.
ExamDle S
Phenobarbital 15.0 mg Ethanol 50.0 mg 1~a~e ~YIarl!
:
.
:
~ 3~
Glycerol monoricinoleate (Softigen 701) 150.0 m~, Fill-in weight 215.0 m8 Phenobarbital was dissolved in the mixture of ethanol and glycerol monoricinoleate and filled into soft gelatin capsules, the capsules were unobjectionable with respect to capsule hardness and capsule appearance.
While in the foregoing there has been provided a detailed description of preferred embodiments of the present invention, it is to be understood that all equivalents obvious to those of ordinary skill in the art are to be included within the scope of the invention as claimed, :
This is confirmed by the European Patent Publication 0 170 623 which employs ethanol as a solvent for the active substance dihydro-(val)2-cyclosporine. Drink solutions contain l0 to 12% by weight of ethanol, whereas the soft gelatin capsules according to Example 2 contain only from 2 to 5% by weight.
lt has now surprisingly found that ethanol mixtures having an cthanol content in excess of 5% by weight7 up to about 50% by weight, can also be encapsulated without the addition of ethylene glycols to form stable preparations, if the solvent mixture contains at least 20%, up to about 95% by weight of partial glycerides of fatty acids having from 6 to 18 carbon atoms. A preferred range of ethanol is about l0-30% by weight and a preferred range of the partial glycerides of fatty acids is 40-90% by weight. Partial glycerides of fatty acids having , from 6 to 12 carbon atoms and/or ricinoleic acid are preferred to be employed.
. .
.
... ,~................................. .
, DETAILED DESCRIPTION OF
THE PREFERRED EMBODIMENT
The gelatin capsules which are the subject of the present invention comprise a gelatin shell which encloses a filling including an active substance, a dietetic agent or a foodstuff and a solvent mixture, the solvent mixture containing about 5-50% (preferably 10-30% by weight~ by weight of ethanol and about 20-95% by weight (preferably 40-90% by weight) of one or more partial glycerides of fatty acids having from 6-18 carbon atoms. The partial glycerides useful in the fill include monoglycerides o} diglycerides as well as mixtures thereof.
Suitable commercially available products inclucle, for example, glycerol ,~ monocaprylate (Imwitor * 308 of Dynamit Nobel), glycerol monodicaprylate (Imwitor 908), mixtures comprising glycerol mor odicaprylate and glycerol monodicaprate (Imwitor 742) and partial glycerldes of ricinoleic acid (Softigen~701 and Rilanit).
These partial glycerides are readily miscible with ethanol and even allow amounts of ethanol in excess of 10% to be employed in the solvent mixture without any deterioration of ~he stability of the gelatin envelope.
The gelatin capsules accordin8 to the present invention are prepared by dissolving the active substance in the mixture of ethanol and partial glycerides. As the ethanol-partial glyceride mixtures are miscible with lipophilic as well as hydrophilic components, various additives may be used if required, e.g. triglycerides of various fatty 2 5 acids or polyethylene glycols~ provided that they do not impair the stability of the active substances or of the gelatin shell of thc capsule.
The solutions according to the invention may be filled into hard gelatin capsules as well as into soft gelatin capsules. The envelope of soft gelatin capsules usually contain.s one or more plasticizers in addition to gelatin, such as glycerol, propylene glycol, sorbitol, or sorbitans. The shell may also contain colorants, preservatives, flavoring agents, sugar and other polyols.
When using soft gelatin capsules or softgels, the capsules are : 35 simultaneously formed and filled with a fill material using conventional . . ' ' : :~
', , : ' .
methods and procedures such as the rotary die process as discussed, for example, in the article of J.P. Stanley, "lI. Soft Gelatin Capsules,"
pp. 360-384, The Theorv and Practice of Industrial Pharmacv. Soft gel capsules or softgels conventionally comprise gelatin, a plasticizer, such as glycerin, or sorbitol and water. The gelatin shells also commonly contain a preservative, such as mixed parabens, for cxample, methyl or propyl parabens. The parabens are incorporated into the shell formulation in minor proportions as compared to the total weight of the shell formulation. Conventional soft gelatin capsules utilize gelatin having a bloom value of 150 to 200 although this value may be varied The fill material can vary over a wide range and may contain unit dosage amounts of pharmaceuticals, dietary supplements, vitamins and the like, often in liquid form. The capsules are commonly sized and shaped so as to be readily swallowable by a person, usually with the aid of water.
The invention is further illustrated by way of the following examples.
Exam~le I
A mixture of 300 mg of glycerol monocaprylate (]mwitor 30B) and 150 mg of ethanol was filled into soft gelatin capsules in a known manner according to the Rotary Die Process, and thc capsules wcre dried. Then the ethanol content of the capsule envelope was analyzcd, and an ethanol content of 4.5% was ~ound. The capsules were physically stable; capsule shape and capsule hardness were excellent.
Comr)arative Exam~e I
400 mg of ethanol were filled into soft gelatin capsules as in El~ample 1. After drying the ethanol content of the capsule envelope was 14.0%. The capsules were physically instable, deformed and shrinked due to the ethanol loss.
ComDarative ExarnDle 2 The mixture of 350 mg of medium-chain triglycerides (Miglyol 812) and 100 mg of ethanol were filled into soft gelatin capsules as in Example l. After drying the ethanol content of the capsule envelope ~6 Ei~
was 11.8%. The capsules were physically instable. They were soft and def ormed.
ExamDle 2 A mixture of 300 mg of glycerol mono/dioleate and I S0 mg of ethanol were filled into soft gelatin capsules as in Example 1. After drying the ethanol content of the capsule envelope was 7.8%. The capsule shape was satisfactory, but the capsules were softer than those of Example I because of the higher ethanol content in the envelope.
Exam~le 3 Hard gelatin capsules of size O having an average weight of 97 mg were filled with a mixture of 80% of glycerol monocaprylate (Imwitor 308) and 20% of ethanol and sealed with a gelatin filament. After one week the ethanol content of the capsule envelope was analyzed. The capsule envelopes contained 2% of ethanol, based on 97 mg of capsule 1 5 envelope.
Com~arative ExamDle 3 Hard gelatin capsules of size O as in Example 3 were filled with a mixture of 80% of medium-chain triglycerides ~Miglyol 812) and 20% of ethanol and sealed with a gelatin filament. After one week tlle ethanol content of the capsulç envelope was 11.1%, based on 97 mg of capsule envelope.
Examl)le 4 Pentetrazol100 mg Ethanol 20 mg Imwitor 742100 m~
Fill-in weight 220 mg Ethanol was added to the molten Imwitor 742, and the Pentctrazol was dissolved in the mixture. The finished solution was filled into soft gelatin capsules of size 4 minims. The dried capsules were 3 0 unobjectionable with respect to capsule hardness and capsule appearance.
ExamDle S
Phenobarbital 15.0 mg Ethanol 50.0 mg 1~a~e ~YIarl!
:
.
:
~ 3~
Glycerol monoricinoleate (Softigen 701) 150.0 m~, Fill-in weight 215.0 m8 Phenobarbital was dissolved in the mixture of ethanol and glycerol monoricinoleate and filled into soft gelatin capsules, the capsules were unobjectionable with respect to capsule hardness and capsule appearance.
While in the foregoing there has been provided a detailed description of preferred embodiments of the present invention, it is to be understood that all equivalents obvious to those of ordinary skill in the art are to be included within the scope of the invention as claimed, :
Claims (16)
1. A capsule having a gelatin shell and the filling therein, said filling comprising an active material and a solvent, said solvent containing at least 5% by weight of ethanol and at least 20% by weight of partial glycerides of fatty acids having from 6-18 carbon atoms.
2. The capsule of claim 1 wherein said active substance is a dietary substance.
3. The capsule of claim 1 wherein said active substance is a food supplement.
4. The capsule of claim 1 wherein said active substance is a pharmaceutical substance.
5. The capsule of claim 1 wherein said ethanol is present in an amount of about 5-50% by weight and said partial glycerides of fatty acids are present in an amount of about 20-95% by weight.
6. The capsule of claim 1 wherein said ethanol is present in an amount of about 10-30% by weight and said partial glycerides of fatty acids are present in an amount of about 40-90% by weight.
7. The capsule of Claim 1 wherein said partial glycerides of fatty acids have from 6-12 carbon atoms.
8. The capsule of claim 1 wherein said partial glycerides of fatty acids is ricinoleate acid.
9. A process for preparing a gelatin capsule of the type having a gelatin shell and a fill material enclosed within said gelatin shell, said process comprising the steps of dissolving an active substance in a solvent, said solvent containing at least 5% by weight of ethanol and at least 7% by weight of partial glycerides of fatty acids having from 6-18 carbon atoms, and filling the solution into the gelatin capsule.
10. The process of claim 9 wherein said active substance is a dietary substance.
11. The process of claim 9 wherein said active substance is a food supplement.
12. The process of claim 9 wherein said active substance is a pharmaceutical substance.
13. The process of claim 9 wherein said ethanol is present in an amount of about 5-50% by weight and said partial glycerides of fatty acids are present in an amount of about 20-95% by weight.
14. The process of claim 9 wherein said ethanol is present in an amount of about 10-30% by weight and said partial glycerides of fatty acids are present in an amount of about 40-90% by weight.
15. The process of Claim 9 wherein said partial glycerides of fatty acids have from 6-12 carbon atoms.
16. The process of claim 9 wherein said partial glycerides of fatty acids is ricinoleate acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3629386.5 | 1986-08-29 | ||
| DE19863629386 DE3629386A1 (en) | 1986-08-29 | 1986-08-29 | GELATINE CAPSULES AND METHOD FOR THEIR PRODUCTION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1296628C true CA1296628C (en) | 1992-03-03 |
Family
ID=6308451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000545611A Expired - Lifetime CA1296628C (en) | 1986-08-29 | 1987-08-28 | Ethanol fill formulation for softgels containing vitamins, dietary supplements and the like |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4888239A (en) |
| EP (1) | EP0257386B1 (en) |
| JP (1) | JPH0830006B2 (en) |
| KR (1) | KR930008955B1 (en) |
| AT (1) | ATE68967T1 (en) |
| AU (1) | AU607434B2 (en) |
| CA (1) | CA1296628C (en) |
| DE (2) | DE3629386A1 (en) |
| ES (1) | ES2025601T3 (en) |
| GR (1) | GR3003036T3 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6007840A (en) * | 1988-09-16 | 1999-12-28 | Novartis Ag | Pharmaceutical compositions comprising cyclosporins |
| KR0148748B1 (en) * | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | A multiphase cyclosporin composition |
| GB8904182D0 (en) * | 1989-02-23 | 1989-04-05 | Glaxo Canada | Pharmaceutical compositions |
| DE4025912A1 (en) * | 1990-08-16 | 1992-02-20 | Werner Ratjen | ORAL INGREDIENTS |
| US6262022B1 (en) | 1992-06-25 | 2001-07-17 | Novartis Ag | Pharmaceutical compositions containing cyclosporin as the active agent |
| US5141961A (en) * | 1991-06-27 | 1992-08-25 | Richrdson-Vicks Inc. | Process for solubilizing difficulty soluble pharmaceutical actives |
| JP3121080B2 (en) * | 1991-12-19 | 2000-12-25 | アール・ピー・シーラー コーポレイション | Encapsulation solution |
| ATE147619T1 (en) | 1992-05-13 | 1997-02-15 | Sandoz Ag | OPTHALMIC COMPOSITIONS CONTAINING A CYCLOSPORIN |
| ES2168271T3 (en) | 1992-09-25 | 2002-06-16 | Novartis Ag | PHARMACEUTICAL COMPOSITIONS CONTAINING CYCLOSPORINS. |
| US5376688A (en) * | 1992-12-18 | 1994-12-27 | R. P. Scherer Corporation | Enhanced solubility pharmaceutical solutions |
| US5431916A (en) * | 1993-04-29 | 1995-07-11 | The Procter & Gamble Company | Pharmaceutical compositions and process of manufacture thereof |
| US20020099067A1 (en) * | 1993-07-08 | 2002-07-25 | Ulrich Posanski | Pharmaceutical compositions for sparingly soluble therapeutic agents |
| DE69435104D1 (en) | 1993-09-28 | 2008-07-31 | Scherer Gmbh R P | Production of soft gelatine capsules |
| US5484606A (en) * | 1994-01-24 | 1996-01-16 | The Procter & Gamble Company | Process for reducing the precipitation of difficulty soluble pharmaceutical actives |
| CA2231404C (en) | 1994-11-03 | 2009-02-17 | Arzneimittelwerk Dresden Gmbh | Novel cyclosporine preparation forms for oral administration of simple composition and high bio-availability, and process for producing them |
| DE19544507B4 (en) | 1995-11-29 | 2007-11-15 | Novartis Ag | Cyclosporin containing preparations |
| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| DE29824679U1 (en) | 1997-01-30 | 2002-03-28 | Novartis Ag | Pharmaceutical compositions |
| DE69804624T2 (en) * | 1997-07-29 | 2002-09-19 | Upjohn Co | SELF-TEMPERATURE FORMULATION CONTAINING LIPOPHILE COMPOUNDS |
| SI0999826T1 (en) * | 1997-07-29 | 2004-12-31 | Pharmacia & Upjohn Company | Self-emulsifying formulation for lipophilic compounds |
| US6063401A (en) | 1998-05-06 | 2000-05-16 | M.E. Cody Products, Inc. | Plantago major and hypericum perforatum compound for use in treating a tobacco or nicotine habit |
| US6045825A (en) | 1998-06-17 | 2000-04-04 | M. E. Cody Products, Inc. | Plantago major and Piper methysticum compound for use in treating a tobacco or nicotine habit |
| US6346231B1 (en) * | 1999-10-06 | 2002-02-12 | Joar Opheim | Flavored gelatin capsule and method of manufacture |
| US20030124225A1 (en) * | 1999-11-01 | 2003-07-03 | Paul West | Encapsulated alcoholic beverage |
| US7732404B2 (en) | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
| KR100393920B1 (en) * | 2000-11-28 | 2003-08-06 | 주식회사 서흥캅셀 | Gelatin hard capsule reducing the static electricity and enhancing the lubrication of surface |
| ITMI20011401A1 (en) * | 2001-07-02 | 2003-01-02 | Altergon Sa | PHARMACEUTICAL FORMULATIONS FOR THYROID HORMONES |
| JP4156234B2 (en) * | 2001-12-27 | 2008-09-24 | 日本メナード化粧品株式会社 | Soft capsule |
| CN1655770A (en) * | 2002-04-25 | 2005-08-17 | 旗帜药物胶囊公司 | Chewable soft capsule |
| CN101141953A (en) * | 2005-03-21 | 2008-03-12 | 伊瓦克斯制药有限公司 | Crystallization inhibitor and its use in gelatin capsules |
| US20150118365A1 (en) * | 2013-10-31 | 2015-04-30 | Steven J. Hollenkamp | Alcohol containing beads and method for making same |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4062799A (en) * | 1973-01-30 | 1977-12-13 | Fuji Photo Film Co., Ltd. | Method of forming microcapsule films having low porosity |
| US4029758A (en) * | 1975-12-15 | 1977-06-14 | Hoffmann-La Roche Inc. | Preparation of pharmaceutical unit dosage forms |
| BE861612A (en) * | 1977-12-07 | 1978-06-07 | Kali Chemie Pharma Gmbh | HIGHLY RESORBABLE PREPARATIONS BY ENTERAL ROUTE OF LITTLE RESORBABLE MEDICINES AND PROCESS FOR THE PREPARATION OF THESE |
| US4627850A (en) * | 1983-11-02 | 1986-12-09 | Alza Corporation | Osmotic capsule |
| US4717566A (en) * | 1984-03-19 | 1988-01-05 | Alza Corporation | Dosage system and method of using same |
| NZ211078A (en) * | 1984-03-19 | 1987-08-31 | Bristol Myers Co | Oral dosage form of etoposide |
| DE3500103A1 (en) * | 1985-01-04 | 1986-07-10 | R.P. Scherer GmbH, 6930 Eberbach | PHARMACEUTICAL PREPARATION WITH AN INTENSIVE SOLUTION IN WATER AND DIGESTIVE JUICES |
| US4717568A (en) * | 1985-08-09 | 1988-01-05 | Alza Corporation | Laminar arrangement for increasing delivery of beneficial agent from dispenser |
-
1986
- 1986-08-29 DE DE19863629386 patent/DE3629386A1/en active Granted
-
1987
- 1987-08-05 AT AT87111310T patent/ATE68967T1/en not_active IP Right Cessation
- 1987-08-05 ES ES198787111310T patent/ES2025601T3/en not_active Expired - Lifetime
- 1987-08-05 EP EP87111310A patent/EP0257386B1/en not_active Expired - Lifetime
- 1987-08-05 DE DE8787111310T patent/DE3774210D1/en not_active Expired - Lifetime
- 1987-08-25 US US07/089,065 patent/US4888239A/en not_active Expired - Lifetime
- 1987-08-28 AU AU77655/87A patent/AU607434B2/en not_active Expired
- 1987-08-28 CA CA000545611A patent/CA1296628C/en not_active Expired - Lifetime
- 1987-08-29 JP JP62216277A patent/JPH0830006B2/en not_active Expired - Lifetime
- 1987-08-29 KR KR1019870009524A patent/KR930008955B1/en not_active IP Right Cessation
-
1991
- 1991-10-31 GR GR91401480T patent/GR3003036T3/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR3003036T3 (en) | 1993-02-17 |
| EP0257386B1 (en) | 1991-10-30 |
| DE3629386C2 (en) | 1988-06-23 |
| KR930008955B1 (en) | 1993-09-17 |
| EP0257386A3 (en) | 1989-05-03 |
| DE3774210D1 (en) | 1991-12-05 |
| AU7765587A (en) | 1988-03-03 |
| ATE68967T1 (en) | 1991-11-15 |
| AU607434B2 (en) | 1991-03-07 |
| JPS63132826A (en) | 1988-06-04 |
| ES2025601T3 (en) | 1992-04-01 |
| US4888239A (en) | 1989-12-19 |
| DE3629386A1 (en) | 1988-03-03 |
| KR880002512A (en) | 1988-05-09 |
| JPH0830006B2 (en) | 1996-03-27 |
| EP0257386A2 (en) | 1988-03-02 |
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Legal Events
| Date | Code | Title | Description |
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| MKEX | Expiry |