Crystalline forms of vilazodone hydrochloride and vilazodone free base

Abstract

The present application relates to crystalline and amorphous Vilazodone hydrochloride. The present application further relates to amorphous solid dispersions of vilazodone hydrochloride with pharmaceutically acceptable carriers. The present application also relates to a process for the preparation of form I of vilazodone free base.

1 - 78 . (canceled) 
     
     
         79 . Crystalline form of vilazodone hydrochloride wherein the crystalline form is selected from a group of:
 form B of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 7.10, 14.96, 17.31 and 21.64±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 7.10, 14.96, 17.31 19.63, 21.64, 22.40, 22.99, 25.91 and 26.72±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 7.10, 12.10, 12.66, 14.96, 17.31 19.63, 21.64, 22.40, 22.99, 25.91 and 26.72±0.2 degrees 2θ;   form C of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 10.50, 14.20 and 20.20±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 9.06, 10.50, 14.20 and 20.20±0.2 degrees 2θ;   form D of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 13.39, 13.67, 16.00, 21.22 and 24.61±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 5.53, 9.60, 10.54, 11.09, 13.39, 13.67, 16.00, 21.22 and 24.61±0.2 degrees 2θ;   form E of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 10.62, 16.18 and 21.42±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 5.55, 9.54, 10.62, 11.06, 16.18 and 21.42±0.2 degrees 2θ;   form F of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 13.45, 13.73, 21.24 and 24.85±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 10.65, 11.07, 13.45, 13.73, 16.07, 21.24 and 24.85±0.2 degrees 2θ; powder X-ray diffraction (PXRD) pattern having peaks at about 5.55, 9.61, 10.65, 11.07, 13.45, 13.73, 15.31, 16.07, 21.24 and 24.85±0.2 degrees 2θ; and   form H of vilazodone hydrochloride characterized by powder X-ray diffraction (PXRD) pattern having peaks at about 19.72, 20.92, 25.25 and 26.26±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 8.45, 12.46, 18.54, 19.18, 19.72, 20.92, 25.25 and 26.26±0.2 degrees 2θ; or powder X-ray diffraction (PXRD) pattern having peaks at about 8.45, 12.46, 13.08, 16.25, 18.54, 19.18, 19.72, 20.92, 25.25 and 26.26±0.2 degrees 2θ.   
     
     
         80 . The crystalline form B of vilazodone hydrochloride of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 1  or  FIG. 2  or  FIG. 3  or  FIG. 4  or  FIG. 5 . 
     
     
         81 . The crystalline Form C of vilazodone hydrochloride of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 6  or  FIG. 7  or  FIG. 8 . 
     
     
         82 . The crystalline vilazodone hydrochloride form D of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 9 . 
     
     
         83 . The crystalline vilazodone hydrochloride form E of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 10 . 
     
     
         84 . The crystalline vilazodone hydrochloride form F of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 11 . 
     
     
         85 . The crystalline form G of vilazodone hydrochloride of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 13 . 
     
     
         86 . The crystalline form H of vilazodone hydrochloride of  claim 79 , characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 14 . 
     
     
         87 . Process for preparing crystalline form B of vilazodone hydrochloride of  claim 79 , which comprises:
 a) providing a mixture of vilazodone free base in suitable solvent or mixtures thereof;   b) combining hydrochloric acid with the mixture of step a);   c) isolating crystalline form B of vilazodone hydrochloride; and   d) optionally drying and humidifying crystalline form B of vilazodone hydrochloride.   
     
     
         88 . Process for preparing crystalline form C of vilazodone hydrochloride of  claim 79 , by drying the crystalline form B of vilazodone hydrochloride with a suitable drying technique. 
     
     
         89 . Process for preparing crystalline form D of vilazodone hydrochloride of  claim 79 , which comprises:
 a) providing a solution of vilazodone hydrochloride in dimethyl sulfoxide solvent;   b) combining ethyl acetate with the solution of step a); and   c) isolating crystalline form D of vilazodone hydrochloride.   
     
     
         90 . Process for preparing crystalline form E of vilazodone hydrochloride of  claim 79 , which comprises:
 a) providing a solution of vilazodone hydrochloride in N-methyl-2-pyrrolidone solvent;   b) combining dichloromethane with the solution of step a); and   c) isolating crystalline form E of vilazodone hydrochloride.   
     
     
         91 . Process for preparing crystalline form F of vilazodone hydrochloride of  claim 79 , which comprises:
 a) providing a solution of vilazodone hydrochloride in N,N-dimethylformamide solvent;   b) combining ethyl acetate with the solution of step a); and   c) isolating crystalline form F of vilazodone hydrochloride.   
     
     
         92 . (canceled) 
     
     
         93 . Process for preparing crystalline form H of vilazodone hydrochloride of  claim 79 , which comprises:
 a) providing a mixture of vilazodone free base in suitable solvent or mixtures thereof;   b) combining hydrochloric acid with the mixture of step a);   c) isolating crystalline vilazodone hydrochloride; and   d) stirring crystalline vilazodone hydrochloride as obtained in step c) in water; and   e) isolating crystalline form H of vilazodone hydrochloride.   
     
     
         94 . (canceled) 
     
     
         95 . An amorphous form of vilazodone hydrochloride wherein the amorphous form is selected from a group of:
 pure amorphous form of vilzodone hydrochloride characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 20 ; and   amorphous solid dispersion of vilazodone hydrochloride with a pharmaceutically acceptable carrier wherein the pharmaceutically acceptable carrier is selected from a group of polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC), characterized by a PXRD pattern which is substantially as illustrated in the pattern of  FIG. 12 .   
     
     
         96 . Process for preparing amorphous solid dispersion of vilazodone hydrochloride of  claim 95 , with a pharmaceutically acceptable carrier, which comprises:
 a) providing a mixture of vilazodone hydrochloride and pharmaceutically acceptable carrier in suitable solvent or mixtures thereof;   b) heating the mixture to obtain a clear solution; and   c) isolating amorphous solid dispersion of vilazodone hydrochloride with a pharmaceutically acceptable carrier.   
     
     
         97 . Pharmaceutically acceptable dosage form comprising amorphous form of vilazodone hydrochloride of  claim 95  and one or more pharmaceutically acceptable excipients. 
     
     
         98 . A process for preparing vilazodone free base comprising the condensation of 5-(piperazin-1-yl)benzofuran-2-carboxamide with 3-(4-chlorobutyl)-1H-indole-5-carbonitrile in a suitable solvent in presence of a base and an additive selected from a group of an ionic additive, a phase transfer catalyst and mixture thereof.