Polymorphs of atomoxetine hydrochloride

Abstract

The present invention provides novel crystalline polymorph forms of atomoxetine hydrochloride denominated Forms B and C and methods for their preparation, as well as methods for the preparation of Form A. The present invention provides pharmaceutical compositions that comprise atomoxetine hydrochloride Form B, Form C, or mixtures thereof that can be used to treat attention deficit/hyperactivity disorder.

1 . A process for the preparation of a crystalline form of atomoxetine hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta comprising the steps of:
 a) combining atomoxetine base in a solvent selected from C 1-4  alcohol, C 2-4  alkyl ester, C 1-4  alkyl ether, mixtures thereof, and C 1-6  substituted or unsubstituted aromatic hydrocarbon to obtain a mixture;   b) combining the mixture with hydrochloric acid or hydrogen chloride to obtain a precipitate; and   c) recovering atomoxetine hydrochloride Form A from the precipitate.   
   
   
       2 . The process of  claim 1 , wherein the solvent is selected from methanol, ethanol, isopropanol, methyl acetate, ethyl acetate, n-butyl acetate, iso-butyl acetate, methyl t-butyl ether, and mixtures thereof, toluene and xylene. 
   
   
       3 . The process of  claim 1 , wherein the solvent is selected from the group consisting of: isopropyl alcohol, methyl-t-butyl ether, ethyl acetate, and mixtures thereof. 
   
   
       4 . A crystalline form of atomoxetine hydrochloride characterized by an x-ray powder diffraction pattern substantially as depicted in  FIG. 2 . 
   
   
       5 . A crystalline form of atomoxetine hydrochloride characterized by an infrared absorption spectrum substantially as depicted in  FIG. 5 . 
   
   
       6 . A crystalline form of atomoxetine hydrochloride characterized by a Raman absorption spectrum substantially as depicted in  FIG. 7 . 
   
   
       7 . A crystalline form of atomoxetine hydrochloride characterized by an x-ray powder diffraction pattern substantially as depicted in  FIG. 3 . 
   
   
       8 . A crystalline form of atomoxetine hydrochloride characterized by a Raman absorption spectrum, substantially as depicted in  FIG. 8 .