Topical montelukast for treatment of atopic dermatitis

Abstract

A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof, a gelling agent and water for the treatment of atopic dermatitis.

1 . A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof, a gelling agent and water for the treatment of atopic dermatitis. 
     
     
         2 . The topical formulation of  claim 1 , wherein the concentration of Montelukast tor its pharmaceutically acceptable salt is between about 0.5 % w/w to about 5 % w/w or between about 5 % w/w to about 10 % w/w. 
     
     
         3 . The topical formulation of  claim 1 , wherein the concentration of montelukast or a pharmaceutically acceptable salt is 5 %w/w. 
     
     
         4 . The topical formulation of  claim 1 , wherein between about 0.5% to about 1% of Montelukast is deposited within the skin following topical application. 
     
     
         5 . The topical formulation of  claim 1 , wherein the pH of the formulation is less than 6. 
     
     
         6 . The topical formulation of  claim 1 , wherein the pH is in the range 5 to 6. 
     
     
         7 . The topical formulation of  claim 1 , wherein the formulation further comprises a water miscible organic solvent. 
     
     
         8 . The topical formulation of  claim 1 , wherein the formulation further comprises a penetration enhancer. 
     
     
         9 . The topical formulation of  claim 1 , wherein the formulation further comprises an antioxidant. 
     
     
         10 . The topical formulation of  claim 1 , wherein the formulation further comprises a preservative. 
     
     
         11 . The topical formulation of  claim 1  comprising:
 a) 
                 Category   Ingredient     Active   Montelukast sodium     Water miscible organic solvent   Alcohol 96%     Penetration enhancer   DMSO     Antioxidant   BHT                       
                 Chelating Agent   EDTA     Water   Purified water     Preservative   Methyl paraben     Preservative   Propyl paraben     Gelling agent   Hydroxyethylcellulose (M w 90,000 to 1,300,000)     pH adjusting agent   HCl (10% solution)                        
 b) 
                 Category of ingredient   Example of Ingredient     Occlusive ingredient   Dimethicone     Occlusive ingredient   Cyclomethicone     Active   Montelukast sodium     Emulsifier   Silicone Glycerol emulsifier     Occlusive ingredient   Cetearyl Ethylhexanoate     Water miscible organic solvent   Glycerin     Solvent   Water     Gelling agent   Sodium Carbomer     Lubricant   Sodium Hyaluronate                            
 c) 
                 Category of ingredient   Example of Ingredient     Active   Montelukast sodium     Water miscible organic solvent   Alcohol     Antioxidant   BHT     Water   Purified water     Penetration enhancer   DMSO     Preservative   Methyl paraben     Preservative   Propyl paraben     Gelling agent   Carbopol 947P(polymers of acrylic acid)     Chelating agent   EDTA     Emulsifier/Thickener/Stabilizer   Sepineo 600 (Acrylamide /Sodium Acryloyldimethyl Taurate copolymer /isohexadecane and Polysorbate 80)                             
 d) 
                 Category of ingredient   Example of Ingredient     Active   Montelukast sodium     Water miscible organic solvent   Alcohol     Antioxidant   BHT     Water   Purified water     Penetration enhancer   DMSO     Preservative   Methyl paraben     Preservative   Propyl paraben     Gelling agent   Carbopol 947P(polymers of acrylic acid)     Chelating agent   EDTA     Emulsifier/Thickener/Stabilizer   Sepineo 600(Acrylamide /Sodium Acryloyldimethyl Taurate copolymer /isohexadecane and Polysorbate 80)     pH adjusting agent   Phosphate or citric acid Buffer                              
 . 
 
     
     
         12 . A topical formulation as in  claim 11  selected from any one of the following 
 a) 
                     Category   Ingredient   % W/W     Active   Montelukast sodium   5.00     Water miscible organic solvent   Alcohol 96%   25.00     Penetration enhancer   DMSO   10.00     Antioxidant   BHT   0.10     Chelating Agent   EDTA   0.10     Water   Purified water   57.90     Preservative   Methyl paraben   0.30     Preservative   Propyl paraben   0.10     Gelling agent   Hydroxyethylcellulose (M w  90,000 to 1,300,000)   1.50     pH adjusting agent   HCl (10% solution)   q.s.                             
 b) 
                     Category of ingredient   Ingredient   % W/W     Occlusive ingredient   Dimethicone   1     Occlusive ingredient   Cyclomethicone   4     Active   Montelukast sodium   3     Emulsifier   Silicone Glycerol emulsifier   1.5                       
                     Occlusive ingredient   Cetearyl Ethylhexanoate   2.5     Water miscible organic solvent   Glycerin   3.0     Solvent   Water   Up to 100     Gelling agent   Sodium Carbomer   2.5     Lubricant   Sodium Hyaluronate   1.0                       
 c) 
                     Category of ingredient   Ingredient   % W/W     Active   Montelukast sodium   1%     Water miscible organic solvent   Alcohol   25%     Antioxidant   BHT   0.10%     Water   Purified water   60.00     Penetration enhancer   DMSO   10.00%     Preservative   Methyl paraben   0.30%     Preservative   Propyl paraben   0.10%     Gelling agent   Carbopol 947P (polymers of acrylic acid)   0.40%     Chelating agent   EDTA   0.10%     Emulsifier/Thickener/Stabilizer   Sepineo 600 (Acrylamide /Sodium Acryloyldimethyl Taurate copolymer /isohexadecane and Polysorbate 80   3%                             
 d) 
                     Category of ingredient   Ingredient   % W/W     Active   Montelukast sodium   1%     Water miscible organic solvent   Alcohol   25%     Antioxidant   BHT   0.10%     Water   Purified water   60.00     Penetration enhancer   DMSO   10.00%     Preservative   Methyl paraben   0.30%     Preservative   Propyl paraben   0.10%     Gelling agent   Carbopol 947P (polymers of acrylic acid)   0.40%     Chelating agent   EDTA   0.10%     Emulsifier/Thickener/Stabilizer   Sepineo 600 ( Acrylamide /Sodium   3%         Acryloyldimethyl Taurate copolymer /isohexadecane and Polysorbate 80         pH adjusting agent   Phosphate Buffer   pH 5.6                               
 . 
 
     
     
         13 . The topical formulation of  claim 1 , wherein the montelukast is homogeneously suspended in the formulation or wherein montelukast crystals are present in the formulation. 
     
     
         14 . A topical formulation comprising Montelukast or a pharmaceutically acceptable salt thereof and at least one oil for the treatment of atopic dermatitis wherein the formulation is waterless. 
     
     
         15 . A topical formulation as in  claim 14  wherein the formulation further comprises a topically acceptable solvent, and an amphiphilic compound and further an occlusive ingredient. 
     
     
         16 . A topical formulation as in  claim 15  selected from any of the following :
 a solution comprising 
                 Category of ingredient   Example     Topically acceptable solvent   Alcohol (Dehydrated)     Amphiphilic compound   Poloxylhydrogenated Castor oil     Active   Montelukast sodium     Oil   Fractionated Coconut oil                       
 or a gel formulation comprising 
                 Category of ingredient   Example of ingredient     Topically acceptable solvent   Alcohol (Dehydrated)     Amphiphilic compound   Poloxylhydrogenated Castor oil     Active   Montelukast sodium     Oil   Fractionated Coconut oil     Gelling agent   Hydroxypropylcellulose                        
 or an ointment comprising 
                 Category of ingredient   Example of Ingredient     Active   Montelukast sodium     Occlusive ingredient   Petroleum jelly/white petrolatum     Oil   Trihydroxystearin     Oil   Olive oil                       
 or an ointment comprising 
                 Category of ingredient   Example of Ingredient     Active   Montelukast sodium     Water miscible organic solvent   Glycerine     Oil   Medium chain triglycerides     Antioxidant   Antioxidant                       
 or an ointment comprising 
                 Category of ingredient   Example of Ingredient     Active   Montelukast Sodium     Antioxidant   BHT     Occlusive ingredient   Cyclomethicone 5, NF     Occlusive ingredient   Cyclomethicone and Dimethicone 5225C                       
 or an ointment comprising 
                 Category of ingredient   Example of Ingredient     Active   Montelukast Sodium     Antioxidant   BHT     Occlusive ingredient   Petrolatum White USP     Amphiphilic compound   Propylene Glycol-15 Stearyl Ether     Oil   Medium Chain Triglycerides     Amphiphilic compound   Monosteol(propylene glycol monostearate)                         
 or an ointment comprising 
                     Category of ingredient   Example of Ingredient     Active   Montelukast Sodium     Antioxidant   BHT     Occlusive ingredient/   Petrolatum White USP     Oil   Mineral Oil                       
 . 
 
     
     
         17 . A topical formulation as in  claim 16  selected from any one of the following:
 a solution comprising 
                     Category of Ingredient   Ingredient   % W/W     Topically acceptable   Alcohol (Dehydrated)   34.5     Amphiphilic compound   Poloxylhydrogenated Castor   2.5     Active   Montelukast sodium   3     oil   Fractionated Coconut oil   60                       
 or a gel formulation comprising 
                     Category of ingredient   Ingredient   % W/W     Topically acceptable solvent   Alcohol (Dehydrated)   31     Amphiphilic compound   Poloxylhydrogenated Castor   2.5     Active   Montelukast sodium   3     oil   Fractionated Coconut oil   60     Gelling agent   Hydroxy propyl cellulose   3.5                        
 . 
 or an ointment comprising 
                     Category of ingredient   Ingredient   % W/W     Active   Montelukast sodium   0.5-5     Occlusive ingredient   Petroleum jelly/white petrolatum   80     Oil   Trihydroxystcarin   1 -3     oil   Olive oil   12- 18.5                       
 or an ointment comprising 
                     Category of ingredient   Ingredient   % W/W′     Active   Montelukast sodium   0.5-5     Water miscible organic solvent   Glycerine   65-75     Oil   Medium chain triglycerides   20     Antioxidant   Antioxidant   0-0.5                       
 or an ointment comprising 
                     Category of ingredient   Ingredient   % W/W′     Active   Montelukast Sodium   5     Antioxidant   BHT   0.08     Occlusive ingredient   Cyclomethicone   94.52     Amphiphilic compound   Cyclomethicone and Dimethicone   0.40                       
 or an ointment comprising 
                     Category of ingredient   Ingredient   % W/W′     Active   Montelukast Sodium   5     Antioxidant   BHT   0.08     Occlusive ingredient   Petrolatum White   55.92     Amphiphilic compound   PPG-15 Stearyl Ether   16     Oil   Medium Chain Triglycerides   20     Amphiphilic compound   Monostcol   3                         
 or an ointment comprising 
                     Category of ingredient   Ingredient   % W/W′     Active   Montelukast Sodium   5     Antioxidant   BHT   0.08     Occlusive ingredient/   Petrolatum White   49.92     Oil   Mineral Oil   45                       
 .