Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof

Abstract

The present invention relates to novel essentially pure venlafaxine and the process of preparation thereof. The present invention also relates to novel solvate forms of venlafaxine hydrochloride and the process of preparation thereof. Furthermore, the present invention provides a novel process for preparing venlafaxine hydrochloride from venlafaxine; the process comprises the steps of: i) preparing a mixture of venlafaxine with acetone; and ii) exposing the mixture in gaseous hydrochloric acid.

What is claimed is:  
     
         1 . A crystalline venlafaxine base in the form of white crystals, wherein the venlafaxine base has a purity of at least about 97%.  
     
     
         2 . A crystalline venlafaxine base in the form of white crystals, wherein the venlafaxine base has a purity of at least about 98%.  
     
     
         3 . A crystalline venlafaxine base in the form of white crystals, wherein the venlafaxine base has a purity of at least about 99%.  
     
     
         4 . A crystalline venlafaxine base in the form of white crystals, wherein the venlafaxine base has a purity of at least about 99.3%  
     
     
         5 . A crystalline venlafaxine base in the form of white crystals, wherein the venlafaxine base has a purity of at least about 99.5%.  
     
     
         6 . A process for preparing a crystalline venlafaxine base having a purity of at least about 97% comprising the steps of: 1) preparing a mixture of N,N-didesmethyl venlafaxine in a first organic solvent; 2) adding a basic solution selected from the group to the mixture to adjust to a basic pH; and 3) extracting the venlafaxine base with a second organic solvent.  
     
     
         7 . The process according to  claim 6 , wherein the purity is at least about 98%.  
     
     
         8 . The process according to  claim 7 , wherein the purity is at least about 99%.  
     
     
         9 . The process according to  claim 8 , wherein the purity is at least about 99.3%.  
     
     
         10 . The process according to  claim 9 , wherein the purity is at least about 99.5%.  
     
     
         11 . The process according to one of claims  6 - 10 , where the basic solution is selected from the group consisting of sodium hydroxide and potassium hydroxide.  
     
     
         12 . The process according to one of claims  6 - 10 , wherein the first organic solvent is formic acid and formaldehyde.  
     
     
         13 . The process according to one of claims  6 - 10 , wherein the second organic solvent is selected from the group consisting of toluene and heptane.  
     
     
         14 . The process according to one of claims  6 - 10 , further comprises drying the second organic solvent to dryness.  
     
     
         15 . The process according to  claim 14 , wherein the drying is carried out by heating or under vacuum.  
     
     
         16 . The process according to one of claims  6 - 10 , further comprising the step of 4) crystallizing venlafaxine base from a solvent selected from the group consisting of hexane, pentane and petroleum-ether.  
     
     
         17 . A crystalline venlafaxine base having a purity of at least about 97% produced according to one of claims  6 - 10 .  
     
     
         18 . A crystalline venlafaxine base having a purity of at least about 98% produced according to one of claims  6 - 10 .  
     
     
         19 . A crystalline venlafaxine base having a purity of at least about 99% produced according to one of claims  6 - 10 .  
     
     
         20 . A crystalline venlafaxine base having a purity of at least about 99.3% produced according to one of claims  6 - 10 .  
     
     
         21 . A crystalline venlafaxine base having a purity of at least about 99.5% produced according to one of claims  6 - 10 .  
     
     
         22 . A process for preparing venlafaxine hydrochloride Form I, comprising the steps of: 
 1) preparing a mixture of venlafaxine in isopropanol; and    2) introducing hydrochloric acid until a pH is in the range of pH about 5 to about 8.    
     
     
         23 . The process according to  claim 22 , wherein the pH is between pH about 6 to about 7.5.  
     
     
         24 . The process according to  claim 22 , wherein the pH is about 7.  
     
     
         25 . The process according to  claim 22 , wherein the hydrochloric acid is a gaseous hydrochloric acid.  
     
     
         26 . The process according to  claim 22 , wherein the venlafaxine is a venlafaxine base.  
     
     
         27 . The process according to  claim 22 , wherein the mixture is a homogeneous solution of venlafaxine.