Novel succinate salt of O-desmethyl-venlafaxine

Abstract

A novel salt of O-desmethyl venlafaxine is provided, O-desmethylvenlafaxine succinate. Pharmaceutical compositions, dosage forms and methods of use are also provided.

What is claimed:  
     
         1 . A method of preparing O-desmethyl-venlafaxine comprising the step of demethylating venlafaxine or a salt thereof with an alkali metal salt of a trialkyl borohydride.  
     
     
         2 . The method of  claim 1 , wherein each alkyl group in the trialkyl borohydride is independently a C 1 -C 6  alkyl.  
     
     
         3 . The method of  claim 2 , wherein the alkali metal salt of a trialkyl borohydride is selected from L-selectride, K-selectride, lithium triethylborohydride, potassium triethylborohydride, and mixtures thereof.  
     
     
         4 . The method of  claim 3 , wherein the alkali metal salt of a trialkyl borohydride is L-selectride.  
     
     
         5 . The method of  claim 1 , wherein the demethylation step is performed at a temperature of from about 60 to about 140° C.  
     
     
         6 . The method of  claim 1 , further comprising the step of converting the O-desmethyl-venlafaxine to O-desmethyl-venlafaxine succinate.  
     
     
         7 . The method of  claim 1 , further comprising the step of deactivating any boron containing byproducts produced by the demethylation reaction.  
     
     
         8 . The method of  claim 7 , wherein the deactivating step comprises oxidizing the boron containing byproducts.  
     
     
         9 . The method of  claim 8 , wherein the oxidizing step comprises reacting the boron containing byproducts with an oxidizing agent selected from hydrogen peroxide, sodium perborate, and mixtures thereof.  
     
     
         10 . The method of  claim 8 , wherein the oxidizing step comprises adding the boron containing byproducts to an oxidizing agent or a solution comprising an oxidizing agent.  
     
     
         11 . A method of preparing O-desmethyl-venlafaxine comprising the steps of: 
 (a) demethylating venlafaxine or a salt thereof with an alkali metal salt of a trialkyl borohydride to yield an alkali metal salt of O-desmethyl-venlafaxine; and    (b) converting the alkali metal salt of O-desmethyl-venlafaxine to the free base of O-desmethyl-venlafaxine.    
     
     
         12 . The method of  claim 11 , wherein step (b) comprises neutralizing the alkali metal salt of O-desmethyl-venlafaxine with acid.  
     
     
         13 . The method of  claim 11 , further comprising the step of (c) converting the free base of O-desmethyl-venlafaxine to O-desmethyl-venlafaxine succinate.  
     
     
         14 . The method of  claim 11 , wherein the venlafaxine in step (a) is the free base of venlafaxine.  
     
     
         15 . A sustained release formulation comprising O-desmethyl-venlafaxine succinate and a pharmaceutically acceptable carrier or excipient, wherein the sustained release formulation provides peak serum levels of up to about 225 ng/ml.