Stabilized azithromycin compositions

Abstract

Compositions and methods of stabilizing azithromycin compositions are described. Stabilized azithromycin compositions comprise an intimate admixture of azithromycin and a stabilizing-effective amount of an antioxidant to improve the resistance of the azithromycin to degradation. Coprecipitation or co-milling of azithromycin and an antioxidant are particularly preferred means of achieving an intimate admixture. Pharmaceutical formulations comprising a stabilized azithromycin composition and methods of making such formulations are also described.

1 . A stabilized azithromycin composition comprising an intimate admixture of azithromycin and a stabilizing-effective amount of an antioxidant.  
     
     
         2 . The azithromycin composition according to  claim 1 , wherein less than about 3.5% of the azithromycin is degraded on exposure to 55° C. for seven days.  
     
     
         3 . The azithromycin composition according to  claim 1 , wherein less than about 1.25% of the azithromycin is degraded on exposure to 50° C. for 20 hours.  
     
     
         4 . The azithromycin composition according to  claim 1 , wherein the intimate admixture is achieved by coprecipitation of the azithromycin and the antioxidant.  
     
     
         5 . The azithromycin composition according to  claim 1 , wherein the intimate admixture is achieved by co-milling the azithromycin and the antioxidant.  
     
     
         6 . The azithromycin composition according to  claim 1 , wherein the intimate admixture is achieved by compaction or slugging of the azithromycin and the antioxidant.  
     
     
         7 . The azithromycin composition according to  claim 1 , wherein the azithromycin is azithromycin ethanolate monohydrate.  
     
     
         8 . The azithromycin composition according to  claim 1 , wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, ascorbic acid, a pharmaceutically acceptable salt or ester thereof, and mixtures thereof.  
     
     
         9 . The azithromycin composition according to  claim 1 , wherein the antioxidant is present in amount of from about 0.01% to about 10% by weight azithromycin.  
     
     
         10 . The azithromycin composition according to  claim 1 , wherein the antioxidant is present in an amount of from about 0.1% to about 5% by weight azithromycin.  
     
     
         11 . The azithromycin composition according to  claim 1 , wherein the antioxidant is butylated hydroxytoluene.  
     
     
         12 . The azithromycin composition according to  claim 1 , wherein the antioxidant is sodium ascorbate.  
     
     
         13 . A pharmaceutical formulation comprising the stabilized azithromycin composition of  claim 1  and a carrier, wherein the pharmaceutical formulation is in a form selected from the group consisting of a tablet, granulate, dragee, capsule, powder, solution, emulsion and suspension.  
     
     
         14 . The pharmaceutical formulation according to  claim 13 , wherein the formulation is in a form of a tablet or capsule.  
     
     
         15 . The pharmaceutical formulation according to  claim 14 , wherein the formulation is in the form of a tablet.  
     
     
         16 . The pharmaceutical formulation according to  claim 13 , wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, ascorbic acid, a pharmaceutically acceptable salt or ester of one of these compounds, and mixtures thereof.  
     
     
         17 . The pharmaceutical formulation according to  claim 16 , wherein the antioxidant is butylated hydroxytoluene.  
     
     
         18 . The pharmaceutical formulation according to  claim 16 , wherein the antioxidant is present in an amount of from about 0.01% to about 10% by weight azithromycin.  
     
     
         19 . The pharmaceutical formulation according to  claim 16 , wherein the antioxidant is present in an amount of from about 0.1% to about 5% by weight azithromycin.  
     
     
         20 . The pharmaceutical formulation according to  claim 13 , wherein the stabilized azithromycin composition is made by dissolving azithromycin and an antioxidant in a solvent followed by evaporation of the solvent.  
     
     
         21 . The pharmaceutical formulation according to  claim 20 , wherein the azithromycin is azithromycin ethanolate monohydrate.  
     
     
         22 - 34  (Canceled).  
     
     
         35 . A method of treating a bacterial infection in a human or non-human animal in need of such treatment comprising administering to said human or non-human animal a pharmaceutical formulation comprising a stabilized azithromycin composition wherein said composition comprises an intimate admixture of azithromycin and a stabilizing-effective amount of an antioxidant.