Ziprasidone free from colored impurities and a process for its preparation

Abstract

Ziprasidone base or a pharmaceutically acceptable salt thereof free from colored impurities, in particular those giving the product a “slightly pink to pink” coloration.

1 . A process for the preparation of ziprasidone base or a pharmaceutically acceptable salt thereof, comprising:
 preparing a ziprasidone free base dispersion in a polar protic organic solvent;   reacting the ziprasidone free base with an organic acid to obtain a resulting addition salt;   separating and recovering the resulting addition salt;   preparing crystalline ziprasidone hydrochloride by displacing the organic acid by reaction with hydrochloric acid in water-alcohol mixture; and   recovering anhydrous ziprasidone hydrochloride, and optionally, converting to ziprasidone free base and/or to another pharmaceutically acceptable salt thereof.   
   
   
       2 . The process according to  claim 1 , wherein the polar protic organic solvent is an alkanol. 
   
   
       3 . The process according to  claim 1 , wherein the organic acid is a sulfonic acid. 
   
   
       4 . The process according to  claim 3 , wherein the sulfonic acid is camphorsulfonic acid, either as single (S) or (R) enantiomer or as a racemic mixture thereof. 
   
   
       5 . The process according to  claim 1 , wherein hydrochloric acid is added in two subsequent portions. 
   
   
       6 . The process according to  claim 1 , wherein the Ziprasidone base or a pharmaceutically acceptable salt thereof is free from colored impurities. 
   
   
       7 . The process according to  claim 1 , wherein the Ziprasidone base or a pharmaceutically acceptable salt thereof is selected from the group consisting of anhydrous ziprasidone hydrochloride, ziprasidone hydrochloride hemi-hydrate, mono-hydrate ziprasidone, ziprasidone mesylate di-hydrate and ziprasidone mesylate tri-hydrate. 
   
   
       8 . The process according to  claim 7  wherein the Ziprasidone base or a pharmaceutically acceptable salt thereof is anhydrous ziprasidone hydrochloride in the form of particles having mean diameter above 85 μm and purity degree equal to or higher than 99.9%.