Stable corticosteroid compositions

Abstract

The invention relates to pharmaceutical compositions comprising a corticosteroid and an antioxidant. The invention further relates to methods of treating, preventing, or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract comprising administering the pharmaceutical compositions comprising a corticosteroid and an antioxidant.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a corticosteroid and an antioxidant, wherein the antioxidant comprises a combination of ascorbic acid and a pharmaceutically acceptable salt of ascorbate, and wherein the pharmaceutical composition does not substantially degrade in the presence of oxygen. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the composition does not substantially comprise impurities formed by oxidative degradation after one month of storage. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the composition does not substantially discolor after one month of storage. 
     
     
         4 . The pharmaceutical composition of any one of  claims 1 - 3 , wherein the composition does not substantially comprise impurities formed by oxidative degradation and does not substantially discolor after two months of storage. 
     
     
         5 . The pharmaceutical composition of any one of  claims 1 - 4 , wherein the composition does not substantially comprise impurities formed by oxidative degradation and does not substantially discolor after three months of storage. 
     
     
         6 . The pharmaceutical composition of any one of  claims 1 - 5 , wherein after two months of storage the composition comprises less than 0.2% impurities formed by oxidative degradation. 
     
     
         7 . The pharmaceutical composition of any one of  claims 1 - 6 , wherein the corticosteroid is budesonide. 
     
     
         8 . The pharmaceutical composition of any one of  claims 1 - 7 , wherein the corticosteroid is budesonide and the antioxidant is a combination of ascorbic acid and sodium ascorbate. 
     
     
         9 . The pharmaceutical composition of any one of  claims 2 - 8 , wherein the corticosteroid is budesonide, the antioxidant is a combination of ascorbic acid and sodium ascorbate, and the impurities formed by oxidative degradation comprise 21-dehydrobudesonide. 
     
     
         10 . The pharmaceutical composition of any one of  claims 1 - 9  having a pH of between about 4 and about 5.2. 
     
     
         11 . The pharmaceutical composition of any one of  claims 1 - 10 , further comprising a preservative. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the preservative is selected from sodium benzoate and potassium sorbate. 
     
     
         13 . The pharmaceutical composition of any one of  claims 1 - 12 , wherein the combination of the ascorbic acid and the salt of ascorbate is present in an amount of from about 0.01% to about 0.5% w/w of the composition. 
     
     
         14 . A method of treating, preventing, or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising a corticosteroid and an antioxidant, wherein the antioxidant comprises a combination of ascorbic acid and a pharmaceutically acceptable salt of ascorbate. 
     
     
         15 . The method of  claim 14 , wherein the corticosteroid is budesonide. 
     
     
         16 . The method of  claim 14  or  15 , wherein the corticosteroid is budesonide and the antioxidant is a combination of ascorbic acid and sodium ascorbate. 
     
     
         17 . The method of any of  claims 14 - 16 , wherein the subject is less than 16 years old. 
     
     
         18 . The method of any of  claims 14 - 17 , wherein the subject is less than 12 years old. 
     
     
         19 . The method of any of  claims 14 - 18 , wherein the method of treating, preventing, or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract is a method of treating the symptoms of and inflammation associated with inflammatory diseases and conditions of the esophagus. 
     
     
         20 . The method of any of  claims 14 - 19 , wherein the inflammatory disease of the esophagus is eosinophilic esophagitis. 
     
     
         21 . A kit for treating, preventing, or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract in a subject in need thereof, comprising a pharmaceutical composition comprising a corticosteroid and an antioxidant, wherein the antioxidant comprises a combination of ascorbic acid and a pharmaceutically acceptable salt of ascorbate, and wherein the pharmaceutical composition does not substantially degrade in the presence of oxygen. 
     
     
         22 . The kit of  claim 21 , wherein the corticosteroid is budesonide and the antioxidant is a combination of ascorbic acid and sodium ascorbate.