Sertraline hydrochloride form II and methods for the preparation thereof

Abstract

The present invention is directed to Form II of sertraline hydrochloride and novel methods for its preparation. According to the present invention, sertraline hydrochloride Form II may be produced directly form sertraline base or sertraline mandelate. It may also be produced from sertraline hydrochloride solvate and hydrate forms, and crystallized from new solvent systems. Pharmaceutical compositions containing sertraline hydrochloride Form II and methods of treatment using such pharmaceutical compositions are also disclosed.

1 . Sertraline Hydrochloride Form II made by a process comprising the steps of:
 (a) dissolving sertraline base or sertraline mandelate in an organic solvent to form a solution;   (b) adding hydrogen chloride to the solution;   (c) heating the solution to a temperature between about room temperature and about reflux for a time sufficient to induce the formation of sertraline hydrochloride Form II; and   (d) isolating sertraline hydrochloride Form II.   
   
   
       2 . Sertraline hydrochloride Form II made by a process comprising the steps of:
 (a) dissolving sertraline hydrochloride in a solvent selected from the group consisting of dimethylformamide, cyclohexanol, acetone and mixtures thereof;   (b) heating the solution for a time sufficient to effect transformation to sertraline hydrochloride Form II; and   (c) isolating sertraline hydrochloride Form II.   
   
   
       3 . Sertraline hydrochloride Form II made by a process comprising the steps of:
 (a) suspending a water or solvent adduct of sertraline hydrochloride in a solvent selected from the group consisting of acetone, t-butyl-methyl ether, cyclohexane, n-butanol, and ethyl acetate, such that a slurry is formed, for a time sufficient to effect transformation to sertraline hydrochloride Form II; and   (b) filtering the slurry to isolate sertraline hydrochloride Form II.   
   
   
       4 . Sertraline hydrochloride Form II. 
   
   
       5 . Sertraline hydrochloride characterized by an x-ray powder diffraction pattern comprising peaks at about 5.5, 11.0, 12.5, 13.2, 14.7, 16.4, 17.3, 18.1, 19.1, 20.5, 21.9, 22.8, 23.8, 24.5, 25.9, 27.5, and 28.0 degrees two theta. 
   
   
       6 . A pharmaceutical composition for the treatment of depression comprising of the sertraline hydrochloride of  claim 5  together with a pharmaceutically acceptable carrier. 
   
   
       7 . A method for treating depression comprising the step of administering to a subject in need of such treatment a therapeutically effective amount of the pharmaceutical composition of  claim 6 .