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.

What is claimed is:  
     
         1 . A process for making sertraline hydrochloride Form II 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 . The process of  claim 1  wherein the solvent is selected form the group consisting of ethyl acetate, acetone, hexane, t-butyl-methyl ether, isopropyl alcohol, n-butanol, t-butanol, iso-butanol, and cyclohexane, and mixtures thereof.  
     
     
         3 . The process of  claim 2  wherein the preferred solvent is t-butyl-methyl ether.  
     
     
         4 . The process of  claim 2  wherein the preferred solvent is n-butanol.  
     
     
         5 . The process of  claim 1  wherein the hydrogen chloride is added as gaseous hydrogen chloride.  
     
     
         6 . The process of  claim 1  wherein the hydrogen chloride is added as a solution of hydrogen chloride.  
     
     
         7 . The process of  claim 6  wherein the solution of hydrogen chloride is selected from the group consisting of isopropyl alcohol and hydrogen chloride, acetone and hydrogen chloride, and n-butanol and hydrogen chloride.  
     
     
         8 . The process of  claim 1  wherein the solution is heated to the reflux temperature of the solvent.  
     
     
         9 . Sertraline hydrochloride Form II made by the process of  claim 1 .  
     
     
         10 . A process for making sertraline hydrochloride Form II 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.    
     
     
         11 . Sertraline hydrochloride Form II made by the process of  claim 10 .  
     
     
         12 . A process for making sertraline hydrochloride Form II comprising the steps of: 
 (a) granulating sertraline hydrochloride Form V in ethanol or methanol; and    (b) stiffing the mixture of sertraline hydrochloride Form V and ethanol or methanol for a time sufficient to induce transformation to sertraline hydrochloride Form II.    
     
     
         13 . Sertraline hydrochloride Form II made by the process of  claim 12 .  
     
     
         14 . A process for making a mixture of sertraline hydrochloride Form II and Form V comprising the steps of: 
 (a) heating sertraline hydrochloride ethanolate Form VI at up to 1 atmosphere pressure; and    (b) isolating a mixture of sertraline hydrochloride Form II and Form V.    
     
     
         15 . A mixture of sertraline hydrochloride Form II and Form V made by the process of  claim 14 .  
     
     
         16 . A process for making sertraline hydrochloride Form II 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.    
     
     
         17 . The process of  claim 16  wherein the process takes place at a temperature between about 25° C. and about 120° C.  
     
     
         18 . The process of  claim 16  wherein the process takes place under reflux conditions.  
     
     
         19 . The process of  claim 16  in which the sertraline hydrochloride is suspended in about 1 to about 10 volumes of organic solvent.  
     
     
         20 . The process of  claim 16  wherein the solvent is t-butyl-methyl-ether.  
     
     
         21 . The process of  claim 16  wherein the solvent is acetone.  
     
     
         22 . The process of  claim 16  wherein the solvent is ethyl acetate.  
     
     
         23 . The process of  claim 16  wherein the solvent is n-butanol.  
     
     
         24 . The process of  claim 16  wherein the sertraline hydrochloride water or solvate adduct is sertraline hydrochloride Form VI.  
     
     
         25 . The process of  claim 16  wherein the sertraline hydrochloride water or solvate adduct is sertraline hydrochloride Form VII.  
     
     
         26 . The process of  claim 16  wherein the sertraline hydrochloride water or solvate adduct is sertraline hydrochloride Form VIII.  
     
     
         27 . Sertraline hydrochloride Form II made by the process of  claim 16 .  
     
     
         28 . Sertraline hydrochloride Form II.  
     
     
         29 . 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.  
     
     
         30 . A pharmaceutical composition for the treatment of depression comprising of the sertraline hydrochloride of  claim 29  together with a pharmaceutically acceptable carrier.  
     
     
         31 . 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  30 .