Polymorphs of esomeprazole salts

Abstract

The present invention relates to a high assayed esomeprazole magnesium dihydrate substantially free of its trihydrate form. The present invention further provides an improved and commercially viable process for preparation of high assayed esomeprazole magnesium dihydrate substantially free of its trihydrate form. The present invention also provides an improved process for preparation of pure amorphous esomeprazole magnesium. The present invention further provides an improved and commercially viable process for preparation of substantially enantiomerically pure esomeprazole in neutral form or as a pharmaceutically acceptable salt or as its solvates including hydrates. The present invention also provides solid form of esomeprazole calcium salt, its polymorphs (form 1, form 2 and amorphous form) and processes for their preparation thereof.

1 - 34 . (canceled) 
     
     
         35 . A process for preparing substantially enantiomerically pure esomeprazole or a pharmaceutically acceptable salt thereof from enantiomerically impure esomeprazole calcium salt; which comprises:
 a) dissolving enantiomerically impure esomeprazole calcium salt in an alcoholic solvent;   b) isolating substantially enantiomerically pure esomeprazole calcium salt as a crystalline solid; and   c) neutralizing the enantiomerically pure esomeprazole calcium salt formed in step (b) with an acid to obtain substantially enantiomerically pure esomeprazole and optionally converting esomeprazole formed into the calcium salt of the enantiomerically pure esomeprazole.   
     
     
         36 . The process as claimed in  claim 35 , wherein the alcoholic solvent used in step (a) is methanol or ethanol. 
     
     
         37 . (canceled) 
     
     
         38 . The process as claimed in  claim 35 , wherein the enantiomerically impure esomeprazole calcium salt in step (a) is dissolved in the alcoholic solvent at a temperature below 60° C. 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . The process as claimed in  claim 35 , wherein the isolation of enantiomerically pure esomeprazole calcium salt in step (b) is carried out by methods such as cooling, partial removal of the solvent from the solution, addition of an anti-solvent or a combination thereof. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The process as claimed in  claim 35 , wherein the acid used in step (c) is an organic or inorganic acid. 
     
     
         45 . The process as claimed in  claim 44 , wherein the organic acid is selected from the group consisting of carboxylic acids such as acetic acid and formic acid; and sulfonic acids such as methane sulfonic acid. 
     
     
         46 . (canceled) 
     
     
         47 . The process as claimed in  claim 44 , wherein the inorganic acid is a mineral acid such as sulfuric acid, hydrochloric acid and phosphoric acid. 
     
     
         48 . (canceled) 
     
     
         49 . (canceled) 
     
     
         50 . The process as claimed in  claim 35 , wherein the neutralization reaction in step (c) is carried out in a solvent system containing water and an organic solvent. 
     
     
         51 . The process as claimed in  claim 50 , wherein the organic solvent is selected from the group consisting of ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate, ethyl formate, methylene dichloride, chloroform, carbontetrachloride, ethylene dichloride, toluene and xylene. 
     
     
         52 . (canceled) 
     
     
         53 . The process as claimed in  claim 35 , wherein the neutralization reaction in step (c) is carried out at a temperature below 40° C. 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . Enantiomerically pure esomeprazole calcium salt. 
     
     
         57 . The compound as claimed in  claim 56 , wherein the esomeprazole calcium salt has a content of the R-omeprazole isomeric impurity of less than about 0.5% by weight. 
     
     
         58 . The compound as claimed in  claim 57 , wherein the esomeprazole calcium salt has a content of isomeric impurity of less than about 0.1% by weight. 
     
     
         59 . The compound as claimed in  claim 58 , wherein the esomeprazole calcium salt has a content of isomeric impurity of less than about  0 . 05 % by weight. 
     
     
         60 . The compound as claimed in  claim 59 , wherein the esomeprazole calcium salt has no traces of the isomeric impurity. 
     
     
         61 - 101 . (canceled) 
     
     
         102 . A pharmaceutical composition comprising the enantiomerically pure esomeprazole calcium salt of  claim 56  and a pharmaceutically acceptable excipient. 
     
     
         103 . A pharmaceutical composition comprising the enantiomerically pure esomeprazole calcium salt of  claim 57  and a pharmaceutically acceptable excipient. 
     
     
         104 . A pharmaceutical composition comprising the enantiomerically pure esomeprazole calcium salt of  claim 58  and a pharmaceutically acceptable excipient. 
     
     
         105 . A pharmaceutical composition comprising the enantiomerically pure esomeprazole calcium salt of  claim 59  and a pharmaceutically acceptable excipient. 
     
     
         106 . A pharmaceutical composition comprising the enantiomerically pure esomeprazole calcium salt of  claim 60  and a pharmaceutically acceptable excipient.