Slow release vehicles for minimizing skin irritancy of topical compositions

Abstract

StapleStable, aqueous gel vehicles are provided for the topical application to the skin of irritating active ingredients such as retinoids, particularly tretinoin, with slow release of the active ingredient and minimal irritancy to the skin. The vehicles include a gelling agent effective to form a gel and hold the active ingredient in the aqueous medium for slow release on the skin, and an effective amount of an antioxidant to retard decomposition of the active ingredient. The vehicles and formulations are preferably aqueous emulsions which contain a solubilizing agent for the generally non-water soluble active ingredients, as well as usually an emulsifying agent and/or surfactant. Chelating agents, emollients, preservatives and other adjuvants and additives may also be included in the vehicles and formulations.

1. A stable, aqueous retinoid composition for topical application to the skin with slow release of the retinoid and minimal irritancy to the skin, comprising:
 (a) an aqueous medium such that the composition is at least about 40 weight percent water;  
 (b) an amount of retinoid effective for topical treatment of a skin condition, wherein said retinoid is tretinoin;  
 (c) an amount of a high molecular weight polyacrylic acid gelling agent neutralized to a pH of about 3 to 7 effective to form a gel and hold said retinoid for slow release in said aqueous medium; and  
 (d) an amount of antioxidant effective to retard decomposition of said retinoid in said aqueous medium.  
 
     
     
       2. A composition according to  claim 1  comprising about 0.01 to 0.1 weight percent retinoid, about 0.1 to 10 weight percent gelling agent, about 0.01 to 4 weight percent antioxidant, and at least about 50 weight percent water. 
     
     
       3. A composition according to  claim 1  wherein said retinoid is selected from the group consisting of tretinoin and effective, dermatologically acceptable salts, isomers and derivatives thereof. 
     
     
       4. A composition according to  claim 1  wherein said antioxidant is selected from the group consisting of dl-alpha-tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, ascorbyl palmitate, and propyl gallate. 
     
     
       5. A composition according to  claim 1  which includes about 0.1 to 20 weight percent of a solubilizing agent for said retinoid. 
     
     
       6. A composition according to  claim 5  wherein said solubilizing agent is ethanol. 
     
     
       7. A composition according to  claim 1  which includes about 0.1 to 20 weight percent of a non-ionic emulsifying agent to form a stable emulsion of said retinoid in water. 
     
     
       8. A composition according to  claim 7  wherein said emulsifying agent comprises at least one normally liquid glycol. 
     
     
       9. A composition according to  claim 1  which contains a surfactant selected from the group consisting of lecithin, sorbitan monoesters, polysorbates, mononylphenyl ethers of polyethyleneglycols, polyoxyethylene monoesters, dioctyl sodium sulfosuccinate, sodium lauryl sulfate, polyoxamers having a molecular weight of 2000 to 8000, triethanolamine, and ureas. 
     
     
       10. A composition according to  claim 1  which includes up to about 10 weight percent of a lipophilic agent. 
     
     
       11. A composition according to  claim 10  wherein said lipophilic agent is selected from the group consisting of fatty alcohols of about 12 to 20 carbon atoms, fatty acid esters having about 12 to 20 carbon atoms in the fatty acid moiety, petrolatum, plant oils and mineral oils. 
     
     
       12. A composition according to  claim 1  which contains about 0.05 to 2 weight percent of a preservative. 
     
     
       13. A composition according to  claim 12  wherein said preservative is selected from the group consisting of methyl paraben, ethyl paraben and sorbitol. 
     
     
       14. A composition according to  claim 1  which includes up to about 0.5 weight percent of a chelating agent for said retinoid. 
     
     
       15. A composition according to  claim 14  wherein said chelating agent is selected from the group consisting of sodium and calcium salts of EDTA. 
     
     
       16. A method for topical treatment of a skin condition with tretinoin with minimal irritancy to the skin, comprising providing the tretinoin in a stable, aqueous composition for slow release of the tretinoin, the composition comprising:
 ( a )  an aqueous medium such that the composition is at least about  40  weight percent water;      ( b )  an amount of tretinoin effective for topical treatment of a skin condition;      ( c )  an amount of a high molecular weight polyacrylic acid gelling agent neutralized to a pH of about  3  to  7  effective to form a gel and hold the tretinoin for slow release in said aqueous medium; and      ( d )  an amount of antioxidant effective to retard decomposition of the tretioin in said aqueous medium;      
       
         and topically applying the composition to the skin to be treated. 
       
     
     
       17. The method according to  claim 16  wherein the composition comprises about  0 . 01  to  0 . 1  weight percent tretinoin, about  0 . 1  to  10  weight percent gelling agent, about  0 . 01  to  4  weight percent antioxidant, and at least about  50  weight percent water. 
     
     
       18. The method according to  claim 16  wherein said antioxidant is selected from the group consisting of dl- alpha - tocopherol, butylated hydroxyanisole, butylated hydroxytoluene, ascorbyl palmitate, and propyl gallate.   
     
     
       19. The method according to  claim 16  wherein the composition includes about  0 . 1  to  20  weight percent of a solubilizing agent for the tretinoin. 
     
     
       20. The method according to  claim 19  wherein said solubilizing agent is ethanol. 
     
     
       21. The method according to  claim 16  wherein the composition includes about  0 . 1  to  20  weight percent of a non- ionic emulsifying agent to form a stable emulsion of the tretinoin in water.   
     
     
       22. The method according to  claim 21  wherein said emulsifying agent comprises at least one normally liquid glycol. 
     
     
       23. The method according to  claim 16  wherein the composition contains a surfactant selected from the group consisting of lecithin, sorbitan monoesters, polysorbates, mononylphenyl ethers of polyethyleneglycols, polyoxyethylene monoesters, dioctyl sodium sulfosuccinate, sodium lauryl sulfate, polyoxamers having a molecular weight of  2000  to  8000 , triethanolamine, and ureas. 
     
     
       24. The method according to  claim 16  wherein the composition includes up to about  10  weight percent of a lipophilic agent. 
     
     
       25. The method according to  claim 24  wherein said lipophilic agent is selected from the group consisting of fatty alcohols of about  12  to  20  carbon atoms, fatty acid esters having about  12  to  20  carbon atoms in the fatty acid moiety, petrolatum, plant oils and mineral oils. 
     
     
       26. The method according to  claim 16  wherein the composition contains about  0 . 05  to  2  weight percent of a preservative. 
     
     
       27. The method according to  claim 26  wherein said preservative is selected from the group consisting of methyl paraben, ethyl paraben and sorbitol. 
     
     
       28. The method according to  claim 16  wherein the composition includes up to about  0 . 5  weight percent of a chelating agent. 
     
     
       29. The method according to  claim 28  wherein said chelating agent is selected from the group consisting of sodium and calcium salts of EDTA.