CA2281837A1 - Solid pharmaceutical composition comprising a retinoid and polyethylene glycol - Google Patents
Solid pharmaceutical composition comprising a retinoid and polyethylene glycol Download PDFInfo
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- CA2281837A1 CA2281837A1 CA 2281837 CA2281837A CA2281837A1 CA 2281837 A1 CA2281837 A1 CA 2281837A1 CA 2281837 CA2281837 CA 2281837 CA 2281837 A CA2281837 A CA 2281837A CA 2281837 A1 CA2281837 A1 CA 2281837A1
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- Prior art keywords
- retinoid
- polyethylene glycol
- capsules
- solid
- peg
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Classifications
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- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- 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
- A61K9/4866—Organic macromolecular compounds
Abstract
Solid pharmaceutical composition comprising a solid solution of a retinoid in polyethylene glycol. Method of making same comprising steps of dissolving the retinoid in molten polyethylene glycol and cooling to solidify the solution.
Description
SOLID PHARMACEUTICAL COMPOSITION
COMPRISING A RETINOID AND
POLYETHYLENE GLYCOL
COMPRISING A RETINOID AND
POLYETHYLENE GLYCOL
BACKGROUND OF THE INVENTION
Vitamin A compounds, also known as retinoids, have been found to be effective in the treatment of various disorders in mammals and particularly in humans.
As used herein, "retinoids" denotes vitamin A in its naturally occurring forms such as retinol, retinal, retinyl esters, and retinoic acid, as well as synthetic analogs of vitamin A. The ring on the analogs may be aromatic or heteroaromatic and the side chain may be optionally substituted with a halide such as chloride. The terminal group may be oxidized, reduced, estefied, etc. The alkali metal (sodium, potassium, etc.) and alkaline earth metal (magnesium, calcium, etc.) salts of a retinoid carboxylic acid are also included herein.
Examples of retinoids included within the present invention are retinoid acid, 13-cis-retinoid acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethylamide, 9-(2,6-dichloro-4-methoxy-5-methyl-Phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester, 4-0-a-D-glucopyranosyl-D-glucopyranosyl-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenate,3,7-dimethyl-9-(2,4,5-trimethyl-3-thienyl)-nona-2,4,6,8-tetraen-1-oic acid ethyl ester, 9-(4-methoxy-2,4,6-trimethyl-phenyl)-4-fluoro-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester and especially 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester.
These compounds and methods for their preparation are known. See e.g., U.S. pat. No. 3,746,730, U.S. Pat. No. 3,931,257, U.S. Pat. No. 3,950,418, U.S. Pat. No. 4,054,589 and U.S. Pat. No. 4,061,656.
13-cis-retinoic acid is also known as isotretinoin.
Vitamin A compounds, also known as retinoids, have been found to be effective in the treatment of various disorders in mammals and particularly in humans.
As used herein, "retinoids" denotes vitamin A in its naturally occurring forms such as retinol, retinal, retinyl esters, and retinoic acid, as well as synthetic analogs of vitamin A. The ring on the analogs may be aromatic or heteroaromatic and the side chain may be optionally substituted with a halide such as chloride. The terminal group may be oxidized, reduced, estefied, etc. The alkali metal (sodium, potassium, etc.) and alkaline earth metal (magnesium, calcium, etc.) salts of a retinoid carboxylic acid are also included herein.
Examples of retinoids included within the present invention are retinoid acid, 13-cis-retinoid acid, 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethylamide, 9-(2,6-dichloro-4-methoxy-5-methyl-Phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester, 4-0-a-D-glucopyranosyl-D-glucopyranosyl-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenate,3,7-dimethyl-9-(2,4,5-trimethyl-3-thienyl)-nona-2,4,6,8-tetraen-1-oic acid ethyl ester, 9-(4-methoxy-2,4,6-trimethyl-phenyl)-4-fluoro-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester and especially 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester.
These compounds and methods for their preparation are known. See e.g., U.S. pat. No. 3,746,730, U.S. Pat. No. 3,931,257, U.S. Pat. No. 3,950,418, U.S. Pat. No. 4,054,589 and U.S. Pat. No. 4,061,656.
13-cis-retinoic acid is also known as isotretinoin.
Belgian patent 762,344 discloses the use of orally administered isotretinoin for the treatment of acne and psoriasis.
U.S. patent 4,322,438 discloses an improved method of treatment of nodulocystic and conglobate acne in humans by oral administration of isotretinoin in regimens which afford an effectively complete remission from the condition even after administration of the compound ceases.
U.S. patent 4,464,394 discloses oral administration of isotretinoin for prophylaxis against development of epithelial carcinomas of the skin, gastrointestinal tract, respiratory tract or genito-urinary tract.
U.S. patent 4,464,394 also discloses compositions in unit dosage forms, including specifically compositions in which the isotretinoin is dispersed in a carrier comprising vegetable oil.
Capsules for oral administration containing isotretinoin are sold in the United States by Roche Laboratories Inc. under the tradename Accutane~. Each capsule contains 10 mg, 20 mg or 40 mg of isotretinoin.
The capsules are in the form of soft gelatin capsules, which comprise a soft gelatin shell filled with a liquid which comprises isotretinoin dispersed in a liquid carrier comprising soybean oil, hydrogenated vegetable oil, hydrogenated soybean oil flakes, beeswax, edetate disodium, and butylated hydroxyanisole.
It is desirable to enable solid compositions for oral administration comprising retinoids, such as tablets or two-piece hard gelatin capsules filled with a solid rather than a liquid, because such compositions are less expensive to manufacture than liquid-filled soft gelatin capsules.
U.S. patent 4,322,438 discloses an improved method of treatment of nodulocystic and conglobate acne in humans by oral administration of isotretinoin in regimens which afford an effectively complete remission from the condition even after administration of the compound ceases.
U.S. patent 4,464,394 discloses oral administration of isotretinoin for prophylaxis against development of epithelial carcinomas of the skin, gastrointestinal tract, respiratory tract or genito-urinary tract.
U.S. patent 4,464,394 also discloses compositions in unit dosage forms, including specifically compositions in which the isotretinoin is dispersed in a carrier comprising vegetable oil.
Capsules for oral administration containing isotretinoin are sold in the United States by Roche Laboratories Inc. under the tradename Accutane~. Each capsule contains 10 mg, 20 mg or 40 mg of isotretinoin.
The capsules are in the form of soft gelatin capsules, which comprise a soft gelatin shell filled with a liquid which comprises isotretinoin dispersed in a liquid carrier comprising soybean oil, hydrogenated vegetable oil, hydrogenated soybean oil flakes, beeswax, edetate disodium, and butylated hydroxyanisole.
It is desirable to enable solid compositions for oral administration comprising retinoids, such as tablets or two-piece hard gelatin capsules filled with a solid rather than a liquid, because such compositions are less expensive to manufacture than liquid-filled soft gelatin capsules.
A difficulty with the manufacture of solid compositions for oral administration containing a retinoid, and in particular isotretinoin, is that retinoids are only sparingly soluble in water; this causes the extent and rate of absorption into systemic circulation after ingestion of a tablet or capsule to be dependent not only on the inactive ingredients (also known as 'excipients') used in the tablet or capsule, but also on the particle size and crystalline form of the retinoid.
It is the object of the present invention to overcome this difficulty, and to enable solid compositions for oral administration comprising a retinoid, wherein the rate and extent of absorption upon oral administration are unaffected, or at least less affected, by the particle size and crystal form of the retinoid that is used.
It is a further object of the present invention to enable solid compositions for oral administration for which the rate and extent of absorption upon oral administration can be well controlled by selection of appropriate quantities of excipients used in the composition.
DESCRIPTION OF THE INVENTION
It has been found that solid solutions of a retinoid in polyethylene glycol can be made by melting the polyethylene glycol, dissolving the retinoid therein, and cooling the solution to form a solid at room temperature.
Upon oral administration, such solid solutions exhibit improved rate and extent of absorption relative to the pure crystalline retinoid; and moreover, the rate and extent of absorption can be controlled by appropriate selection of the ratio of the polyethylene glycol to retinoid. Generally, increased rate and extent of absorption is achieved by use of a higher ratio of polyethylene glycol to retinoid; i.e., a more dilute solid solution.
The ratio of polyethylene glycol to retinoid will preferably be from about 2 to about 30, and most preferably from about 4 to about 15.
It is the object of the present invention to overcome this difficulty, and to enable solid compositions for oral administration comprising a retinoid, wherein the rate and extent of absorption upon oral administration are unaffected, or at least less affected, by the particle size and crystal form of the retinoid that is used.
It is a further object of the present invention to enable solid compositions for oral administration for which the rate and extent of absorption upon oral administration can be well controlled by selection of appropriate quantities of excipients used in the composition.
DESCRIPTION OF THE INVENTION
It has been found that solid solutions of a retinoid in polyethylene glycol can be made by melting the polyethylene glycol, dissolving the retinoid therein, and cooling the solution to form a solid at room temperature.
Upon oral administration, such solid solutions exhibit improved rate and extent of absorption relative to the pure crystalline retinoid; and moreover, the rate and extent of absorption can be controlled by appropriate selection of the ratio of the polyethylene glycol to retinoid. Generally, increased rate and extent of absorption is achieved by use of a higher ratio of polyethylene glycol to retinoid; i.e., a more dilute solid solution.
The ratio of polyethylene glycol to retinoid will preferably be from about 2 to about 30, and most preferably from about 4 to about 15.
5 Because retinoids have low solubility in polyethylene glycols at room temperature are also prone to degradation at elevated temperatures, it was expected that it would not be possible to make satisfactory solid solutions of retinoids in polyethylene glycols.
However, it has surprisingly been found that it is possible to make such solid solutions and to do so without significant degradation in the process of manufacture. This is done by ensuring that, in the process of manufacture, the mixture is heated to the minimum temperature needed to dissolve the required quantity of retinoid in the polyethylene glycol, and by mixing at that temperature only for so long a time as needed, and then promptly cooling the molten solution.
It is preferred to ensure that the mixture is heated to a high enough temperature and for long enough to ensure that all or substantially all of the retinoid is dissolved in the process, in order to make the dissolution characteristics of the final product completely independent of the particle size and crystal form of the retinoid used.
Depending on the solubility of the retinoid in the PEG and.the relative amounts used, the solution may become supersaturated as it cools and there may be some precipitation of the retinoid as the solution cools and solidifies.
The term solid solution as used herein will be understood to mean the resulting solid product, even if some of the retinoid was undissolved or has precipitated. Regardless of whether or not there is some precipitation, the resulting product still has the advantage of having dissolution characteristics independent of the particle size and crystalline form of the retinoid used in the process, if the retinoid was fully dissolved at some point in the process.
However, it has surprisingly been found that it is possible to make such solid solutions and to do so without significant degradation in the process of manufacture. This is done by ensuring that, in the process of manufacture, the mixture is heated to the minimum temperature needed to dissolve the required quantity of retinoid in the polyethylene glycol, and by mixing at that temperature only for so long a time as needed, and then promptly cooling the molten solution.
It is preferred to ensure that the mixture is heated to a high enough temperature and for long enough to ensure that all or substantially all of the retinoid is dissolved in the process, in order to make the dissolution characteristics of the final product completely independent of the particle size and crystal form of the retinoid used.
Depending on the solubility of the retinoid in the PEG and.the relative amounts used, the solution may become supersaturated as it cools and there may be some precipitation of the retinoid as the solution cools and solidifies.
The term solid solution as used herein will be understood to mean the resulting solid product, even if some of the retinoid was undissolved or has precipitated. Regardless of whether or not there is some precipitation, the resulting product still has the advantage of having dissolution characteristics independent of the particle size and crystalline form of the retinoid used in the process, if the retinoid was fully dissolved at some point in the process.
Since retinoids are prone to degradation by oxidation, it is preferred to incorporate in the solid solution an antioxidant such as, for example, a tocopherol, butylated hydroxyanisole, or buylated hydroxytoluene.
Polyethylene glycol is commonly known by the acronym 'PEG'. PEG's of various average molecular weights are sold by Union Carbide Corp. under the tradenarne Carbowax~. The melting range of PEG increases with average molecular weight. For example, the melting range for PEG's of various average molecular weights are as follows:
AVERAGE MOLECULAR WEIGHT MELTING RANGE
PEG1000 1000 37 to 40°C
PEG1450 1450 43 to 46°C
PEG3350 3350 54 to 58°C
PEG8000 8000 .60 to 63°C
Solutions of a retinoid in PEG that are solid at room temperature are enabled by use of any PEG with a melting point of above about 30°C. Generally a higher melting point is more desirable, as a higher melting point PEG provides a harder and less hydroscopic solid at room temperature.
Accordingly, PEG3350 and PEG8000 are preferred.
The solid solution can be used directly as a fill for two-piece hard gelatin capsules. This can be done by filling the solution into the capsules when the solution is still molten, and allowing it to cool and solidify after it is filled into the capsules.
Polyethylene glycol is commonly known by the acronym 'PEG'. PEG's of various average molecular weights are sold by Union Carbide Corp. under the tradenarne Carbowax~. The melting range of PEG increases with average molecular weight. For example, the melting range for PEG's of various average molecular weights are as follows:
AVERAGE MOLECULAR WEIGHT MELTING RANGE
PEG1000 1000 37 to 40°C
PEG1450 1450 43 to 46°C
PEG3350 3350 54 to 58°C
PEG8000 8000 .60 to 63°C
Solutions of a retinoid in PEG that are solid at room temperature are enabled by use of any PEG with a melting point of above about 30°C. Generally a higher melting point is more desirable, as a higher melting point PEG provides a harder and less hydroscopic solid at room temperature.
Accordingly, PEG3350 and PEG8000 are preferred.
The solid solution can be used directly as a fill for two-piece hard gelatin capsules. This can be done by filling the solution into the capsules when the solution is still molten, and allowing it to cool and solidify after it is filled into the capsules.
Alternatively, the molten solution can be allowed to solidify into a solid mass, which can then be ground up into granules. The granules can then be filled into two-piece hard gelatin capsules, either as-is, or after mixing with further excipients, such as, for example, fillers, lubricants and glidants.
Alternatively, the granules can be compressed into tablets on a tablet press, again either as-is, or after mixing with further excipients such as, for example, fillers, binders, lubricants and glidants.
The following examples are illustrative of the invention.
Example 1 120 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
The following were then blended into the molten PEG3350 for about 10 minutes at 125°C.
BUTYLATED HYDROXYANISOLE 0.120 g EDETATE DISODIUM 0.120 g ISOTRETRINOIN 8.00 g The resulting clear solution was then cooled to 70-80°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 641.2 mg per capsule: It follows that each capsule contained 40 mg of isotretinoin in 600 mg of PEG3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
Alternatively, the granules can be compressed into tablets on a tablet press, again either as-is, or after mixing with further excipients such as, for example, fillers, binders, lubricants and glidants.
The following examples are illustrative of the invention.
Example 1 120 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
The following were then blended into the molten PEG3350 for about 10 minutes at 125°C.
BUTYLATED HYDROXYANISOLE 0.120 g EDETATE DISODIUM 0.120 g ISOTRETRINOIN 8.00 g The resulting clear solution was then cooled to 70-80°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 641.2 mg per capsule: It follows that each capsule contained 40 mg of isotretinoin in 600 mg of PEG3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
Example 2 100 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
The following were then blended into the molten PEG3350 for about 10 minutes at 125°C.
BUn~TED HYDROXYANISOLE 0.100 g EDETATE DISODIUM 0.100 g ISOTRETRINOIN 10.00 g The resulting clear solution was then cooled to 90-100°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 440.8 mg per capsule. It follows that each capsule contained 40 mg of isotretinoin in 400 mg of PEG3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
Example 3 80 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
40 g of isotretrinoin was then blended into the molten PEG 3350 for about 10 minutes at 150°C. A substantial portion but not all of the isotretrinoin was dissolved. The molten mass was cooled and allow to solidify. It was then ground up into granules. The granules were filled into two piece hard gelatin capsules at a net fill weight of 120 mg per capsule. It follows that each capsule contained 40 mg of isotretinoin in 80 mg of PEG 3350.
The following were then blended into the molten PEG3350 for about 10 minutes at 125°C.
BUn~TED HYDROXYANISOLE 0.100 g EDETATE DISODIUM 0.100 g ISOTRETRINOIN 10.00 g The resulting clear solution was then cooled to 90-100°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 440.8 mg per capsule. It follows that each capsule contained 40 mg of isotretinoin in 400 mg of PEG3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
Example 3 80 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
40 g of isotretrinoin was then blended into the molten PEG 3350 for about 10 minutes at 150°C. A substantial portion but not all of the isotretrinoin was dissolved. The molten mass was cooled and allow to solidify. It was then ground up into granules. The granules were filled into two piece hard gelatin capsules at a net fill weight of 120 mg per capsule. It follows that each capsule contained 40 mg of isotretinoin in 80 mg of PEG 3350.
Example 4 300 g of PEG 3350 was placed in a glass beaker and heated on a hotplate until melted.
The following were then blended into the molten PG 3350 for about 10 minutes at 100°C:
ISOTRETRINOIN 10.0 g The resulting clear solution was then cooled 70-80°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 310 mg per capsule. It follows that each capsule contained 10 mg of isotretinoin in 300 mg of PEG 3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
BIOAVAILABILITY STUDY
A 3-way comparative bioavailability study was done in 9 human subjects in 3 sessions.
In each session, 3 of the subjects ingested a capsule of example 1, 3 of the subjects ingested a capsule of example 2, and 3 of the subjects ingested a capsule of Accutane~ 40 mg.
Blood samples were taken at numerous times up to 72 hours after ingestion, and the samples were analyzed to determine the drug concentrations. For the capsules of examples 1 and 2, the mean peak concentration (Cmax) relative to Accutane~ and the mean extent of absorption, as indicated by the area under the curve to 72 hours (AUC), relative to Accutane~ were calculated. The results were as follows.
~ ~.,.,., r~....,.,.. ~ ~...,., n . .n Capsules of example 1 206.3% 178.3%
Capsules of example 2 137.9% 123.2%
It can thus be seen that the capsules of examples 1 and 2 both provide higher peak concentrations and also higher extent of absorption than Accutane~.
Also, because of the lower ratio of PEG to isotretinoin, the capsules of example 2 provide lower peak concentration and lower extent of absorption 10 than the capsules of example 1.
A capsule giving peak concentration and extent of absorption equivalent to that of Accutane~ could presumably be made by further reducing the ratio of PEG to isotretinoin.
The following were then blended into the molten PG 3350 for about 10 minutes at 100°C:
ISOTRETRINOIN 10.0 g The resulting clear solution was then cooled 70-80°C and, at that temperature, the liquid was filled into two-piece hard gelatin capsules at a net fill weight of 310 mg per capsule. It follows that each capsule contained 10 mg of isotretinoin in 300 mg of PEG 3350. The contents of the capsules solidified upon cooling of the capsules to room temperature.
BIOAVAILABILITY STUDY
A 3-way comparative bioavailability study was done in 9 human subjects in 3 sessions.
In each session, 3 of the subjects ingested a capsule of example 1, 3 of the subjects ingested a capsule of example 2, and 3 of the subjects ingested a capsule of Accutane~ 40 mg.
Blood samples were taken at numerous times up to 72 hours after ingestion, and the samples were analyzed to determine the drug concentrations. For the capsules of examples 1 and 2, the mean peak concentration (Cmax) relative to Accutane~ and the mean extent of absorption, as indicated by the area under the curve to 72 hours (AUC), relative to Accutane~ were calculated. The results were as follows.
~ ~.,.,., r~....,.,.. ~ ~...,., n . .n Capsules of example 1 206.3% 178.3%
Capsules of example 2 137.9% 123.2%
It can thus be seen that the capsules of examples 1 and 2 both provide higher peak concentrations and also higher extent of absorption than Accutane~.
Also, because of the lower ratio of PEG to isotretinoin, the capsules of example 2 provide lower peak concentration and lower extent of absorption 10 than the capsules of example 1.
A capsule giving peak concentration and extent of absorption equivalent to that of Accutane~ could presumably be made by further reducing the ratio of PEG to isotretinoin.
Claims (8)
1. A solid composition comprising a solid solution of a retinoid in polyethylene glycol.
2. A composition of claim 1 wherein the polyethylene glycol and retinoid are present in a ratio of polyethylene glycol to retinoid by weight of about 2 to about 30.
3. A composition of claim 1 wherein the polyethylene glycol and retinoid are present in a ratio of polyethylene glycol to retinoid by weight of about 4 to about 15.
4. A composition according to Claim 2 or 3 wherein the average molecular weight of polyethylene glycol is from about 3350 to about 8000.
5. A composition of any of claims 1 to 4 further comprising an antioxidant.
6. A composition of any of claims 1 to 5 in the form of a tablet or capsule.
7. A composition of any of claims 1 to 6 wherein the retinoid is isotretinoin.
8. A method of making a composition of any of claims 1 to 7 comprising the steps of melting polyethylene glycol, dissolving the retinoid therein, and cooling to solidify the solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2281837 CA2281837A1 (en) | 1999-09-07 | 1999-09-07 | Solid pharmaceutical composition comprising a retinoid and polyethylene glycol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2281837 CA2281837A1 (en) | 1999-09-07 | 1999-09-07 | Solid pharmaceutical composition comprising a retinoid and polyethylene glycol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2281837A1 true CA2281837A1 (en) | 2001-03-07 |
Family
ID=4164100
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2281837 Abandoned CA2281837A1 (en) | 1999-09-07 | 1999-09-07 | Solid pharmaceutical composition comprising a retinoid and polyethylene glycol |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2281837A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1455730A1 (en) * | 2001-12-06 | 2004-09-15 | Ranbaxy Laboratories, Ltd. | Isotretinoin nanoparticulate compositions |
| WO2004103346A1 (en) * | 2003-05-20 | 2004-12-02 | Ranbaxy Laboratories Limited | Pharmaceutical compositions of acitretin |
-
1999
- 1999-09-07 CA CA 2281837 patent/CA2281837A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1455730A1 (en) * | 2001-12-06 | 2004-09-15 | Ranbaxy Laboratories, Ltd. | Isotretinoin nanoparticulate compositions |
| EP1455730A4 (en) * | 2001-12-06 | 2006-01-18 | Ranbaxy Lab Ltd | Isotretinoin nanoparticulate compositions |
| WO2004103346A1 (en) * | 2003-05-20 | 2004-12-02 | Ranbaxy Laboratories Limited | Pharmaceutical compositions of acitretin |
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