Pharmaceutical composition for transdermal or transmucous administration
The present invention relates to a novel pharmaceutical composition for transdermal or transmucous administration of at least one active substance, and comprising especially a fatty acid as a percutaneous absorption promoter, at least one alcoholic vehicle and also a stabilizer capable of stabilizing the fatty acid in the said pharmaceutical composition.
1. A pharmaceutical composition for transdermal or transmucous administration of at least one active substance, comprising
an active substance,
a fatty acid percutaneous absorption promoter in an amount of between 0.1% and 20%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition,
an alcoholic vehicle comprising an alcohol selected from the group consisting of ethanol and isopropanol, and
a stabilizer capable of stabilizing the fatty acid in said pharmaceutical composition, wherein said stabilizer comprises the fatty acid ester of said fatty acid and said alcohol and is present in an amount of between 0.1% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition and
wherein said composition is in the form of a gel or solution, and
wherein the amount of said fatty acid percutaneous absorption promoter does not vary by more than +/−5% after storage for 6 months at 40° C. and 75% relative humidity.
2. A pharmaceutical composition according to claim 1 , wherein the fatty acid is selected from the group consisting of capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, palmitoleic acid, linoleic acid and linolenic acid.
3. A pharmaceutical composition according to claim 1 , having a pH of between 4 and 10.
4. A pharmaceutical composition according to claim 1 , wherein the fatty acid ester is selected from the group consisting of ethyl oleate, isopropyl oleate, isopropyl myristate, isopropyl palmitate, ethyl octanoate, ethyl dodecanoate, ethyl linoleate and ethyl linolenate.
5. A pharmaceutical composition according to claim 1 , wherein the alcoholic vehicle comprises ethanol.
6. A pharmaceutical composition according to claim 1 , having an alcoholic vehicle content of between 10% and 90%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
7. A pharmaceutical composition according to claim 1 , further comprising a co-solvent selected from the group consisting of glycerol, propylene glycol, polyethylene glycol, and mixtures thereof.
8. A pharmaceutical composition according to claim 7 , having a co-solvent content of between 0.5% and 20% these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
9. A pharmaceutical composition according to claim 1 , being in the form of a gel, and-further comprising between 0.2% and 30% of a gelling agent, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
10. A pharmaceutical composition according to claim 9 , wherein the gelling agent is selected from the group consisting of carbomers, non-preneutralized acrylic polymers, cellulose derivatives, poloxamers, poloxamines, chitosan, dextran pectins, natural gums, and mixtures thereof.
11. A pharmaceutical composition according to claim 9 , further comprising a neutralizer.
12. A pharmaceutical composition according to claim 11 , wherein the neutralizer is selected from the group consisting of triethanolamine, sodium hydroxide, ammonium hydroxide, potassium hydroxide, arginine, aminomethylpropanol and tromethamine, and mixtures thereof.
13. A pharmaceutical composition according to claim 11 , wherein the neutralizer/gelling agent ratio is between 10/1 and 0.1/1.
14. A pharmaceutical composition according to claim 1 , wherein the active substance is selected from the group consisting of oestrogens, progestins, androgens, anti-oestrogens and anti-androgens, or mixtures thereof.
15. A pharmaceutical composition according to claim 14 , having an active substance content of between 0.01% and 5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
16. A pharmaceutical composition according to claim 1 , having a fatty acid content of between 0.2% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
17. A pharmaceutical composition according to claim 1 , having a fatty acid content of between 0.5% and 5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
18. A pharmaceutical composition according to claim 1 , having a pH of between 5 and 9.
19. A pharmaceutical composition according to claim 1 , having a pH of between 6 and 8.
20. A pharmaceutical composition according to claim 1 , having a fatty acid ester content of between 0.2% and 5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
21. A pharmaceutical composition according to claim 1 , having a fatty acid ester content of between 0.5% and 2.5%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
22. A pharmaceutical composition according to claim 1 , having an alcoholic vehicle content of between 20% and 80%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
23. A pharmaceutical composition according to claim 1 , having an alcoholic vehicle content of between 40% and 70%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
24. A pharmaceutical composition according to claim 7 , having a co-solvent content of between 1% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
25. A pharmaceutical composition according to claim 1 , being in the form of a gel, and-further comprising between 0.5% and 10% of a gelling agent, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
26. A pharmaceutical composition according to claim 1 , being in the form of a gel, and-further comprising between 0.3% and 5% of a gelling agent, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition.
27. A pharmaceutical composition according to claim 9 , wherein the gelling agent is selected from the group consisting of carbomers, cellulose derivatives, and mixtures thereof.
28. A pharmaceutical composition according to claim 9 , wherein the gelling agent is selected from the group consisting of Carbopol® 980, hydroxypropylcellulose and mixtures thereof.
29. A pharmaceutical composition according to claim 11 , wherein the neutralizer is selected from the group consisting of triethanolamine, tromethamine, and mixtures thereof.
30. A pharmaceutical composition according to claim 11 , wherein the neutralizer/gelling agent ratio is between 7/1 and 0.5/1.
31. A pharmaceutical composition according to claim 11 , wherein the neutralizer/gelling agent ratio is between 4/1 and 1/1.
32. A pharmaceutical composition for transdermal or transmucous administration of at least one active substance, comprising
an active substance,
oleic acid in an amount of between 0.1% and 20%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition,
an alcoholic vehicle comprising ethanol, and
ethyl oleate in an amount of between 0.1% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition,
wherein said composition is in the form of a gel or solution, and wherein the amount of oleic acid does not vary by more than +/−5% after storage for 6 months at 40° C. and 75% relative humidity.
33. A method of making a pharmaceutical composition for transdermal or transmucous administration of at least one active substance, comprising admixing:
an active substance,
a fatty acid percutaneous absorption promoter in an amount of between 0.1% and 20%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition,
an alcoholic vehicle comprising an alcohol selected from the group consisting of ethanol and isopropanol, and
a stabilizer capable of stabilizing the fatty acid in said pharmaceutical composition, wherein said stabilizer comprises the fatty acid ester of said fatty acid and said alcohol and is present in an amount of between 0.1% and 10%, these percentages being expressed on a weight basis relative to 100 g of pharmaceutical composition,
wherein said composition is in the form of a gel or solution.
34. A pharmaceutical composition made by a method according to claim 33 .