Corticosteriod containing foam compositions

Abstract

The present invention provides a method of manufacturing foamable, corticosteroid containing compositions as well as methods for treating various skin diseases.

What is claimed is: 
     
         1 . A foamable pharmaceutical composition comprising:
 a) a corticosteroid or a pharmaceutically acceptable salt, ester, or solvate thereof;   b) an aliphatic alcohol;   c) at least one foam structuring agent comprising one or more fatty alcohols, non-ionic surfactants, or combinations thereof;   d) a polyol;   e) a can corrosion inhibitor; and   e) water; and   f) a propellant, wherein the composition is void of a buffer.   
     
     
         2 . The composition of  claim 1 , wherein the corticosteroid is selected from the group consisting of methylprednisolone, hydrocortisone, prednisolone, clobetasone, hydrocortisone butyrate, flumetasone, fluocortin, fluperolone, fluorometholone, fluprednidene, desonide, triamcinolone, alclometasone, hydrocortisone buteprate, dexamethasone, clocortolone, betamethasone, fluclorolone, desoximetasone, fluocinolone acetonide, fluocortolone, diflucortolone, fludroxycortide, fluocinonide, budesonide, diflorasone, amcinonide, halometasone, mometasone furoate, methylprednisolone aceponate, beclomethasone, hydrocortisone aceponate, fluticasone, prednicarbate, difluprednate, halobetasol, resocortol butyrate, clobetasol and halcinonide. 
     
     
         3 . The composition of  claim 2 , wherein the corticosteroid is halobetasol. 
     
     
         4 . The composition of  claim 1 , wherein the aliphatic alcohol is methyl, ethyl, isopropyl or butyl alcohol, or a combination thereof. 
     
     
         5 . The composition of  claim 1 , wherein the aliphatic alcohol is ethyl alcohol. 
     
     
         6 . The composition of  claim 1 , wherein the fatty alcohol is selected from the group consisting of lauryl alcohol, myristyl alcohol, cetyl alcohol, lauryl alcohol, stearyl alcohol, octyldodecanol, and combinations thereof. 
     
     
         7 . The composition of  claim 1 , wherein the fatty alcohol is a mixture of cetyl alcohol and stearyl alcohol. 
     
     
         8 . The composition of  claim 1 , wherein the polyol is selected from the group consisting of glycerin, propylene glycol, butylene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol and combinations thereof. 
     
     
         9 . The composition of  claim 1 , wherein the polyol is propylene glycol. 
     
     
         10 . The composition of  claim 1 , wherein the at least one foam structuring agent comprises an ethoxylated alcohol. 
     
     
         11 . The composition of  claim 10 , wherein the ethoxylated alcohol is polyoxyl 20 cetostearyl ether. 
     
     
         12 . The composition of  claim 1 , wherein the at least one foam structuring agent is a combination of one or more of cetyl alcohol, stearyl alcohol, and an ethoxylated alcohol. 
     
     
         13 . The composition of  claim 1 , wherein the at least one foam structuring agent is Emulsifying Wax, NF. 
     
     
         14 . The composition of  claim 1 , wherein the can corrosion inhibitor is less than approximately 0.005%, 0.001% or 0.0005% w/w of benzoic acid. 
     
     
         15 . The composition of  claim 1 , wherein the composition has a pH of about 4.0 to 6.3. 
     
     
         16 . The composition of  claim 1 , wherein the propellant is selected from propane, n-butane, isobutane, n-pentane, isopentane, dichloro difluoro methane, dichloro tetrafluoro ethane, octafluoro cyclobutane, 1,1,1,2-tetrafluoroethane, 1,1-difluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and mixtures of two or more thereof. 
     
     
         17 . The composition of  claim 1 , further comprising one or more members selected from the group consisting of one or more additional therapeutic agents, coloring agents, preservatives, viscosity control agents, and fragrances. 
     
     
         18 . The composition of  claim 1  comprising, on a weight basis:
 a) 0.02 to 0.10% corticosteroid or its pharmaceutically acceptable salts, esters, and solvates; 
 b) 40 to 60% ethyl alcohol; 
 c) 0.1 to 5.0% Emulsifying Wax, NF; 
 d) 0.05 to 1.0% cetostearyl alcohol; 
 e) 0.05 to 1.0% polyoxyl 20 cetostearyl ether; 
 f) 1 to 10% propylene glycol; 
 g) 30 to 40% water; 
 h) less than 0.001% benzoic acid as the can corrosion inhibitor; and 
 i) 3.25 to 5.75% propellant, wherein the composition has a pH of between about 4.0 to 6.3. 
 
     
     
         19 . The composition of  claim 18 , wherein the composition has an acceptable shelf-life of greater than about 24, 27, 30, 33, 36, 39, 42, 45 or 48 months. 
     
     
         20 . The composition of  claim 19 , wherein the composition has an acceptable shelf-life of greater than about 36 months. 
     
     
         21 . The composition of  claim 20 , wherein the shelf-life is determined at International Conference on Harmonisation (ICH) long-term storage condition by:
 a) the 95% one-sided lower confidence interval of the linear regression of the assay for halobetasol or its pharmaceutically acceptable salts, esters, and solvates;   b) the 95% one-sided upper confidence interval of the linear regression of the degradant products for halobetasol or its pharmaceutically acceptable salts, esters, and solvates; or   c) the pH stability of the composition.