Polymorphic forms of ziprasidone HCI and processes for their preparation

Abstract

Provided are various polymorphic forms of ziprasidone HCl and processes for their preparation.

1 . A crystalline form of ziprasidone HCl (Form E), wherein the crystalline form is characterized by a powder XRD pattern with peaks at 7.4, 13.0, 20.7, 23.4, 25.9±0.2 degrees 2 theta.  
     
     
         2 . The crystalline form of  claim 1 , wherein the crystalline form is further characterized by peaks at 13.7, 20.0, 21.3, 25.2±0.2 degrees two-theta.  
     
     
         3 . The crystalline form of  claim 2 , has an XRD pattern as substantially depicted in  FIG. 4 .  
     
     
         4 . A process for preparing ziprasidone HCl of  claim 1 , comprising: 
 a) combining aqueous HCl with ziprasidone base in the presence of ethyl acetate or acetonitrile to obtain a slurry;    b) maintaining the slurry to obtain ziprasidone HCl; and    c) recovering the ziprasidone HCl.    
     
     
         5 . The process of  claim 4 , wherein the ziprasidone base is ziprasidone Form B.  
     
     
         6 . The process of  claim 4 , wherein the slurry temperature is at least about 40° C.  
     
     
         7 . A crystalline form of ziprasidone HCl, wherein the crystalline form is a trihydrate.  
     
     
         8 . The crystalline form of  claim 7 , wherein the crystalline form is a solvated form of ethyl acetate.  
     
     
         9 . The crystalline form of  claim 7 , wherein the crystalline form is a solvated form of acetonitrile.  
     
     
         10 . A process for preparing ziprasidone HCl of  claim 1  in a mixture with a crystalline ziprasidone HCl having an X-Ray diffraction pattern having peaks at about 10.9, 17.4 and 19.1±0.2 degrees 2 theta, comprising: 
 a) combining aqueous HCl with ziprasidone base in the presence of tetrahydrofuran to obtain a slurry;    b) maintaining the slurry to obtain Ziprasidone HCl; and    c) recovering the ziprasidone HCl mixture.    
     
     
         11 . The process of  claim 10 , wherein the slurry is at about room temperature.  
     
     
         12 . Crystalline form of ziprasidone HCl prepared by the processes of any of claims  4  or  10 .