Amorphous form of esomeprazole salts
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. 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 at least one organic solvent, wherein the organic solvent contains an organic amine or ammonia, and
recovering the salt of esomeprazole in the amorphous form from the solution thereof by the removal of the solvent.
2. The process of claim 1 , wherein a cation is selected from the group consisting of Na, Mg, Li, K, Ca, and N(R.).sub.4, where R is a hydrogen or an alkyl group with 1-4 carbon atoms.
3. The process of claim 2 , wherein the cation is Na.
4. The process of claim 2 , wherein the cation is Mg.
5. The process of claim 2 , wherein the cation is K.
6. The process of claim 2 , wherein the cation is Ca.
7. The process of claim 1 , wherein the solvent is at least one of a lower alkanol, ketone, ester, chlorinated solvent, acetonitrile or mixtures thereof.
8. The process of claim 7 , wherein the lower alkanol is selected from a primary, secondary or tertiary alcohol having from one to six carbon atoms.
9. The process of claim 7 , wherein the lower alkanol is methanol, ethanol, denatured spirit, n-propanol, isopropanol, n-butanol, isobutanol, and t-butanol or a mixture thereof.
10. The process of claim 7 , wherein the ketone is selected from acetone, 2-butanone, and 4-methylpentan-2-one or a mixture thereof.
11. The process of claim 7 , wherein the ester is selected from ethyl acetate, n-butyl acetate or a mixture thereof.
12. The process of claim 7 , wherein the chlorinated solvent is selected from chloroform, dichloromethane or a mixture thereof.
13. The process of claim 1 , wherein removing the solvent comprises one or more of distillation, distillation under vacuum, evaporation, spray drying, and freeze drying.
14. The process of claim 1 , wherein the salt of esomeprazole in an amorphous form is recovered from the solution by spray drying.
15. The process of claim 1 , wherein the salt of esomeprazole in an amorphous form is recovered from the solution by freeze-drying.
16. The process of claim 1 , further comprising additional drying of the product obtained.