Amorphous form of esomeprazole salts

Abstract

The invention relates to an amorphous form of the salts of the (−) enantiomer or (S)-enantiomer of omeprazole, i.e., esomeprazole. The invention also relates to processes for preparing amorphous esomeprazole salts and pharmaceutical compositions that include the amorphous esomeprazole salts.

1 . An amorphous form of a salt of esomeprazole.  
     
     
         2 . The amorphous form of a salt of esomeprazole of  claim 1 , wherein a cation is selected from the group consisting Na, Mg, Li, K, Ca, and N(R) 4 , where R is a hydrogen or an alkyl group with 1-4 carbon atoms.  
     
     
         3 . The amorphous form of a salt of esomeprazole of  claim 2 , wherein the cation comprises Na.  
     
     
         4 . The amorphous form of a salt of esomeprazole of  claim 2 , wherein the cation comprises Mg.  
     
     
         5 . The amorphous form of a salt of esomeprazole of  claim 2 , wherein the cation comprises K.  
     
     
         6 . The amorphous form of a salt of esomeprazole of  claim 2 , wherein the cation comprises Ca.  
     
     
         7 . The amorphous form of a salt of esomeprazole of  claim 1 , wherein the esomeprazole salt has the X-ray diffraction pattern of a plain halo.  
     
     
         8 . (Cancelled).  
     
     
         9 . A pharmaceutical composition comprising: 
 a therapeutically effective amount of an amorphous form of a salt of esomeprazole; andone or more pharmaceutically acceptable carriers, excipients or diluents.    
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein a cation is selected from the group consisting of Na, Mg, Li, K, Ca, and N(R) 4 , where R is a hydrogen or an alkyl group with 1-4 carbon atoms.  
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the cation comprises Na.  
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the cation comprises Mg.  
     
     
         13 . The pharmaceutical composition of  claim 10 , wherein the cation comprises K.  
     
     
         14 . The pharmaceutical composition of  claim 10 , wherein the cation comprises Ca.  
     
     
         15 . The pharmaceutical composition of  claim 10 , wherein the esomeprazole salt has the X-ray diffraction pattern of a plain halo of FIG. 1.  
     
     
         16 . (Cancelled)  
     
     
         17 . A process for the preparation of a salt of the amorphous form of esomeprazole, the process comprising: 
 preparing a solution of a salt of esomeprazole in one or more solvents; and    recovering the salt of esomeprazole in the amorphous form from the solution thereof by the removal of the solvent.    
     
     
         18 . The process of  claim 17 , wherein a cation is selected from the group consisting of Na, Mg, Li, K, Ca, and N(R) 4 , where R is a hydrogen or an alkyl group with 1-4 carbon atoms.  
     
     
         19 . The process of  claim 18 , wherein the cation comprises Na.  
     
     
         20 . The process of  claim 18 , wherein the cation comprises Mg.  
     
     
         21 . The process of  claim 18 , wherein the cation comprises K.  
     
     
         22 . The process of  claim 18 , wherein the cation comprises Ca.  
     
     
         23 . The process of  claim 17 , wherein the solvent comprises one or more of lower alkanol, ketone, ester, chlorinated solvent, acetonitrile or mixtures thereof.  
     
     
         24 . The process of  claim 23 , wherein the lower alkanol comprises one or more of primary, secondary and tertiary alcohol having from one to six carbon atoms.  
     
     
         25 . The process of  claim 23 , wherein the lower alkanol comprises one or more of methanol, ethanol, denatured spirit, n-propanol, isopropanol, n-butanol, isobutanol, and t-butanol.  
     
     
         26 . The process of  claim 23 , wherein the lower alkanol comprises one or more of methanol, ethanol, and denatured spirit.  
     
     
         27 . The process of  claim 23 , wherein the ketone comprises one or more of acetone, 2-butanone, and 4-methylpentan-2-one.  
     
     
         28 . The process of  claim 23 , wherein the ester comprises one or more of ethyl acetate and n-butyl acetate.  
     
     
         29 . The process of  claim 23 , wherein the chlorinated solvent comprises one or more of chloroform and dichloromethane.  
     
     
         30 . The process of  claim 17 , wherein removing the solvent comprises one or more of distillation, distillation under vacuum, evaporation, spray drying, and freeze drying.  
     
     
         31 . The process of  claim 17 , wherein the salt of esomeprazole in an amorphous form is recovered from the solution by spray drying.  
     
     
         32 . The process of  claim 17 , wherein the salt of esomeprazole in an amorphous form is recovered from the solution by freeze-drying.  
     
     
         33 . The process of  claim 17 , further comprising additional drying of the product obtained.  
     
     
         34 . The process of  claim 17 , further comprising forming the product obtained into a finished dosage form.  
     
     
         35 . The process of  claim 17 , further comprises adding one or both of an organic amine and ammonia to the solution.  
     
     
         36 . The process of  claim 36 , wherein the organic amine and/or ammonia is added to the solution prior to removal of the solvent.  
     
     
         37 . The process of  claim 17 , wherein the amorphous esomeprazole salt obtained has the X-ray diffraction pattern of a plain halo.  
     
     
         38 . (Cancelled).