Methods of stabilizing azithromycin

Abstract

A method of packaging of azithromycin which provides improved stability of azithromycin upon storage. Additionally, 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 container for packaging azithromycin made of gas impermeable material wherein after storage azithromycin degradation products do not exceed 5% by weight of the azithromycin.  
   
   
       2 . The container according to  claim 1 , wherein after storage azithromycin degradation products do not exceed 3% by weight of azithromycin.  
   
   
       3 . The container according to  claim 1 , wherein the gas impermeable material is laminated aluminum.  
   
   
       4 . The container according to  claim 1 , wherein the container comprises at least two layers of gas impermeable material, wherein at least one of those layers is aluminum.  
   
   
       5 . The container according to  claim 1 , wherein the azithromycin is azithromycin solvate.  
   
   
       6 . The container according to  claim 5 , wherein the azithromycin is selected from the group consisting of ethanol solvate, propanol solvate, and a hydrate.  
   
   
       7 . The container according to  claim 6 , wherein the azithromycin is monohydrate azithromycin.  
   
   
       8 . A container for packaging azithromycin monohydrate made of gas impermeable material wherein after storage less than about 5% of azithromycin monohydrate is transformed to azithromycin dihydrate upon storage of one year.  
   
   
       9 . The container according to  claim 8 , wherein the gas impermeable material is laminated aluminum.  
   
   
       10 . The container according to  claim 1 , wherein the container is in the form of a bag or pouch.  
   
   
       11 . The container according to  claim 1 , wherein the gas impermeable material is impermeable to oxygen.  
   
   
       12 . The container according  claim 1 , wherein the gas impermeable is on the interior of the container.  
   
   
       13 . The container according to  claim 1 , wherein the azithromycin is stored at a temperature of about 25° C. to about 55° C.  
   
   
       14 . The container according to  claim 1 , wherein the azithromycin is stored at 60% relative humidity.  
   
   
       15 . The container according to  claim 1 , wherein the azithromycin is stored for at least one month.  
   
   
       16 . The container according to  claim 1 , wherein the degradation products are identified by HPLC relative to retention times of about 0.26, 0.34, 0.37, or 0.80 as compared to azithromycin.  
   
   
       17 . A method for storing azithromycin comprising packaging azithromycin in a container comprising a gas impermeable material wherein after storage azithromycin degradation products do not exceed 5% by weight of the azithromycin.  
   
   
       18 . The method according to  claim 17 , wherein the gas impermeable material is laminated aluminum.  
   
   
       19 . The method according to  claim 18 , wherein the container comprises at least two layers of gas impermeable material, wherein at least one of those layers is laminated aluminum.  
   
   
       20 . A dry blend, used for forming azithromycin tablets by direct compression, comprising: (a) azithromycin obtained from the packaging of  claim 1;  and (b) at least one pharmaceutically acceptable excipient, wherein said azithromycin is not azithromycin dihydrate.  
   
   
       21 - 102 . (canceled)