Halobetasol foam composition and method of manufacture thereof

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 storage stable, foamable composition comprising on a weight basis:
 a) 0.02 to 0.10% halobetasol 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; and   h) greater than 0.0% and less than 0.0005% benzoic acid,   wherein the composition has a pH of between about 4.0 to 6.3, and   wherein the composition is produced by:   forming a homogenous solution including (b)-(h), wherein the solution is formed in a single batch vessel at a temperature of between about 55° to 75° C. while minimizing the evaporative losses;   cooling the homogenous solution to a temperature of between about 40° to 55° C.;   adding halobetasol, or a pharmaceutically acceptable salt, ester, or solvate thereof, to the cooled solution and forming a homogenous solution while maintaining a temperature of between about 40° to 55° C.;   filling an aerosol canister with the homogenous solution while the solution is maintained at a temperature of between about 40° to 50° C.; and   charging the canister with the propellant thereby forming the foamable composition.   
     
     
         2 . The composition of  claim 1 , wherein the ethyl alcohol and benzoic acid are combined before adding the propylene glycol, polyoxyl 20 cetostearyl ether, cetostearyl alcohol and water. 
     
     
         3 . The composition of  claim 2 , wherein the benzoic acid is added to the ethyl alcohol which is heated to at least about 55° C. before addition of the benzoic acid. 
     
     
         4 . The composition of  claim 1 , wherein the homogenous solution including (b)-(h) is maintained at a temperature of between about 65° to 70° C. 
     
     
         5 . The composition of  claim 1 , wherein the homogenous solution including (b)-(h) is cooled to a temperature of between about 45° to 50° C. 
     
     
         6 . The composition of  claim 1 , wherein filling is performed while maintaining the solution at a temperature of between about 42° to 48° C. 
     
     
         7 . The composition of  claim 1 , wherein the homogenous solution including (b)-(h) is prepared in a suitable vessel to keep evaporative losses below 0.25% w/w during compounding. 
     
     
         8 . The composition of  claim 1 , wherein the halobetasol remains stable for at least three months at 40° C. 
     
     
         9 . The composition of  claim 1 , wherein the propellant is propane, n-butane, isobutane, or combinations thereof, at 3.25 to 5.75% w/w.