Novel forms of tiotropium bromide and processes for preparation thereof

Abstract

This invention relates to novel crystalline forms of tiotropium bromide, processes for preparing them, and their use in pharmaceutical formulations.

1 - 156 . (canceled) 
     
     
         157 . Crystalline Form 11 of tiotropium bromide, characterized by a powder XRD pattern having peaks at 8.9, 16.7, 17.7, 19.1, 20.2, 28.0, 29.0 and 31.2±0.2 degrees 2-theta; and further characterized by:
 an absence of peaks between the peak at 17.7±0.2 degrees 2-theta and the peak at 19.1±0.2 degrees 2-theta; and 
 an absence of peaks between the peak at 28.0±0.2 degrees 2-theta and the peak at 29.0±0.2 degrees 2-theta. 
 
     
     
         158 . The crystalline form of tiotropium bromide according to  claim 157 , further characterized by a powder XRD pattern having peaks at 15.6, 21.7, 23.4, 24.3 and 26.5±0.2 degrees 2-theta. 
     
     
         159 . The crystalline form of tiotropium bromide according to  claim 157 , further characterized by weight loss of about <0.1%, by TGA. 
     
     
         160 . The crystalline form of tiotropium bromide according to  claim 157 , further characterized by a TGA curve as depicted in  FIG. 13 . 
     
     
         161 . The crystalline form of tiotropium bromide according to  claim 157 , further characterized by a DSC thermogram having an endothermic peak at about 227° C. 
     
     
         162 . The crystalline form of tiotropium bromide according to  claim 157 , further characterized by a powder X-ray diffractogram as depicted in  FIG. 12 . 
     
     
         163 . A pharmaceutical formulation comprising the crystalline form of tiotropium bromide according to  claim 157  and a pharmaceutically acceptable excipient. 
     
     
         164 . Crystalline tiotropium bromide, characterized by a powder XRD pattern having peaks at 8.9, 18.7, 17.7, 19.1, 20.2, 28.0, 29.0 and 31.2±0.2 degrees 2-theta, and further characterized by:
 an absence of peaks between the peak at 17.7±0.2 degrees 2-theta and the peak at 19.1±0.2 degrees 2-theta; and 
 an absence of peaks between the peak at 28.0±0.2 degrees 2-theta and the peak at 29.0±0.2 degrees 2-theta; or 
 is characterized by a powder X-ray diffractogram as depicted in  FIG. 12 , 
 wherein said crystalline Tiotropium bromide comprises crystalline Form 11 of tiotropium bromide, and contains no more than about 10% of any other form of tiotropium bromide other than Form 11. 
 
     
     
         165 . The crystalline tiotropium bromide according to  claim 164 , wherein said crystalline tiotropium bromide contains no more than about 5% of any other form of tiotropium bromide other than Form 11.