Topical Pharmaceutical Foam Composition

Abstract

A stable topical alcohol-free aerosol foam containing one or more keratolytic agents is provided. The foam-forming formulation is an emulsion which contains an HFA propellant and one or more keratolytic agents. The emulsion has an oil phase and an aqueous, i.e. water-containing, phase. The active agent(s) may be present in either phase of the emulsion or dispersed in the emulsion. The oil phase may consist at least in part of the HFA propellant. Either or both of the oil phase and the aqueous phase may contain one or more surfactants, emulsifiers, emulsion stabilizers, buffers, and/or other excipients. The foam is stable on the skin, for example, for at least 5 minutes at body temperature, preferably at least 20 minutes at body temperature, and disappears into the skin upon rubbing or after prolonged standing. In one embodiment, the formulation contains an HFA propellant which does not contain additional co-solvents or co-propellants. The formulations demonstrate reduced intensity of the odor and/or color associated with the keratolytic agent(s) as compared to conventional formulations containing keratolytic agents.

1 . A topical aerosol foam formulation comprising: 
 (a) one or more keratolytic agents dissolved or dispersed in an oil-in-water emulsion; and    (b) a propellant consisting essentially of one or more hydrofluoroalkanes contacting the emulsion to produce an immediate foaming action on expulsion from a pressurized container.    
     
     
         2 . The formulation of  claim 1 , wherein the keratolytic agent is selected from the group consisting of urea, salicylic acid, papain, sulfur, glycolic acid, pyruvic acid, alpha hydroxy acids, beta hydroxy acids, resorcinol, N-acetylcysteine, retinoids, retinoic acid, coal tar, derivatives thereof, and combinations thereof.  
     
     
         3 . The formulation of  claim 1 , wherein the concentration of the keratolytic agent is from about 1% to 60%.  
     
     
         4 . The formulation of  claim 1 , further comprising one or more active agents selected from the group comprising of antibiotic agents, antimicrobial agents, anti-acne agents, antibacterial agents, antifungal agents, antiviral agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, anesthetics, antipruriginous agents, antiprotozoal agents, anti-oxidants, antihistamines, hormones, vitamins, skin-soothing agents, suncreens, and combinations thereof.  
     
     
         5 . The formulation of  claim 1 , wherein the foam is stable for at least 5 minutes at body temperature.  
     
     
         6 . The formulation of  claim 1 , wherein the foam is stable for at least 20 minutes at body temperature.  
     
     
         7 . The formulation of  claim 2 , wherein the keratolytic agent is urea.  
     
     
         8 . The formulation of  claim 7 , wherein the amount of urea is from about 5% to about 50% (w/w).  
     
     
         9 . The formulation of  claim 8 , wherein the amount of urea is from about 10% to about 50% (w/w).  
     
     
         10 . The formulation of  claim 8 , wherein the amount of urea is from about 20% to about 40% (w/w).  
     
     
         11 . The formulation of  claim 7 , further comprising ammonium lactate.  
     
     
         12 . The formulation of  claim 11 , wherein the amount of ammonium lactate is from about 1% to about 30% (w/w).  
     
     
         13 . The formulation of  claim 12 , wherein the amount of ammonium lactate is from about 5% to about 20% (w/w).  
     
     
         14 . The formulation of  claim 12 , wherein amount of ammonium lactate is from about 10% to about 15% (w/w).  
     
     
         15 . The formulation of  claim 2 , wherein the keratolytic agent is papain.  
     
     
         16 . The formulation of 15, wherein the papain is present in an amount from about 0.5% to about 40%.  
     
     
         17 . The formulation of 16, wherein the papain is present in an amount from about 1% to about 20%.  
     
     
         18 . The formulation of 16, wherein the papain is present in an amount from about 1% to about 10%.  
     
     
         19 . The formulation of  claim 15 , further comprising urea.  
     
     
         20 . The formulation of  claim 19 , wherein the amount of urea is from about 1% to about 60% (w/w).  
     
     
         21 . The formulation of  claim 20 , wherein the amount of urea is from about 2.5% to about 20% (w/w).  
     
     
         22 . The formulation of  claim 21 , wherein the amount of urea is from about 5% to about 15% (w/w).  
     
     
         23 . The formulation of  claim 19 , further comprising chlorophyllin copper complex sodium.  
     
     
         24 . The formulation of  claim 23 , wherein the amount of chlorophyllin copper complex sodium is from about 0.5% to about 40% (w/w).  
     
     
         25 . The formulation of  claim 24 , wherein the amount of chlorophyllin copper complex sodium is from about 1% to about 20% (w/w).  
     
     
         26 . The formulation of  claim 24 , wherein the amount of chlorophyllin copper complex sodium is from about 1% to about 10% (w/w).  
     
     
         27 . The formulation of  claim 2 , wherein the one or more keratolytic agents are sulfur and sodium sulfacetamide.  
     
     
         28 . The formulation of  claim 27 , wherein the amounts of sulfur and sodium sulfacetamide are each from about 0.01% to about 20% (w/w).  
     
     
         29 . The formulation of  claim 28 , wherein the amounts of sulfur and sodium sulfacetamide are each from about 1% to about 15% (w/w).  
     
     
         30 . The formulation of  claim 28 , wherein the amounts of sulfur and sodium sulfacetamide are each from about 6% to about 12% (w/w).  
     
     
         31 . The formulation of  claim 27 , further comprising one or more agents selected from the group consisting of vitamins, skin-soothing agents, and suncreens.  
     
     
         32 . The formulation of  claim 2 , wherein the keratolytic agent is salicylic acid.  
     
     
         33 . The formulation of  claim 32 , wherein the amount of salicylic acid is from about 1% to about 30% (w/w).  
     
     
         34 . The formulation of  claim 33 , wherein the amount of salicylic acid is from about 4% to about 10% (wlw).  
     
     
         35 . The formulation of  claim 32 , further comprising one or more agents selected from the group consisting of vitamins, skin-soothing agents, and suncreens.  
     
     
         36 . The formulation of  claim 4 , wherein the antibiotic is selected from the group consisting of sodium sulfacetamide, clindamycin, erthyromycin, and metronidazole.  
     
     
         37 . The formulation of  claim 36 , wherein the antibiotic is present in an amount from about 0.01% to about 20% by weight of the composition.  
     
     
         38 . The formulation of  claim 37 , wherein the antibiotic is present in an amount from about 1% to about 15% by weight of the composition.  
     
     
         39 . The formulation of  claim 37 , wherein the antibiotic is present in an amount from about 6% to about 12% by weight of the composition.  
     
     
         40 . The formulation of  claim 1 , further comprising one or more excipients selected from the group consisting of surfactants, emollients, emulsifiers, stabilizing agents, chelating agents, antioxidants, buffers, stabilizers, preservatives and combinations thereof.  
     
     
         41 . The formulation of  claim 1 , wherein the hydrofluorocarbon propellant is present in an amount from about 5% to about 30% by weight of the composition.  
     
     
         42 . The formulation of  claim 1 , wherein the hydrofluorocarbon is selected from the group consisting of 1,1,1,2-tetrafluoroethane (134a); 1,1,1,2,3,3,3-heptafluoropropane (227); and combinations thereof.  
     
     
         43 . The formulation of  claim 1 , wherein the yield stress of the dispensed foam is between 250 and 60,000 dynes/cm 2 .  
     
     
         44 . The formulation of  claim 1 , where the zero shear viscosity of the dispensed foam is between 15,000 and 700,000 cP.  
     
     
         45 . The formulation of  claim 1 , wherein the expansion factor of the dispensed foam is between 1.5 and 15 cm 3 /g.  
     
     
         46 . The formulation of  claim 1 , wherein the foam density is from about 0.1 g/mL to about 0.6 g/mL.  
     
     
         47 . The formulation of  claim 1 , further comprising a fragrance or odor masking agent.  
     
     
         48 . A method of making a topical foam aerosol formulation, the method comprising: 
 (a) making an oil in water emulsion with a predominantly, more than 50%, aqueous phase,    (b) dissolving or dispersing one or more keratolytic agents in the aqueous phase or oil phase prior to emulsification, and    (c) adding a propellant consisting essentially of a hydrofluoroalkane or a mixture of hydrofluoroalkanes, without additional co-solvents or co-propellants, to the emulsion, wherein the emulsion produces an immediate foaming action on expulsion from a pressurized container.    
     
     
         49 . A HFA containing topical foam formulation free of volatile lower alcohols produced by the method of  claim 48.