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 - 74 . (canceled) 
     
     
         75 . A crystalline tiotropium bromide characterized by a powder XRD pattern having peaks at about 20.2, 26.5, 28.0, and 31.2±0.2 degrees 2-theta, and further characterized by an additional powder XRD peak at about 19.1±0.2 degrees 2-theta. 
     
     
         76 . The crystalline tiotropium bromide of  claim 75 , further characterized by a powder XRD pattern having peaks at about 8.9, 15.6, 17.7, 21.7, 23.4, and 24.3±0.2 degrees 2-theta. 
     
     
         77 . (canceled) 
     
     
         78 . The crystalline tiotropium bromide of  claim 75 , further characterized by weight loss of about <0.1%, by TGA. 
     
     
         79 . The crystalline tiotropium bromide of  claim 78  further characterized by a TGA curve as depicted in  FIG. 13 . 
     
     
         80 . The crystalline tiotropium bromide of  claim 75 , further characterized by a DSC thermogram having an endothermic peak at about 227° C. 
     
     
         81 . A process for preparing a crystalline tiotropium bromide according to  claim 75 , comprising heating a Tiotropium bromide solvate to a temperature ranging from about 160° C. to about 170° C. 
     
     
         82 - 129 . (canceled) 
     
     
         130 . Crystalline Tiotropium bromide, characterized by a powder XRD pattern having peaks at about 19.1, 20.2, 26.5, 28.0, and 31.2±0.2 degrees 2-theta, or by a powder X-ray diffractogram as depicted in  FIG. 12 , wherein said form of tiotropium bromide contains no more than about 10% of tiotropium bromide monohydrate. 
     
     
         131 . The Tiotropium bromide of  claim 130 , wherein said form of tiotropium bromide contains no more than about 5% of tiotropium bromide monohydrate. 
     
     
         132 . (canceled) 
     
     
         133 . A pharmaceutical formulation comprising the form of Tiotropium bromide of  claim 75  and a pharmaceutically acceptable excipient. 
     
     
         134 - 152 . (canceled) 
     
     
         153 . Crystalline Tiotropium bromide, characterized by a powder XRD pattern having peaks at about 19.1, 20.2, 26.5, 28.0, and 31.2±0.2 degrees 2-theta, or by a powder X-ray diffractogram as depicted in  FIG. 12 , wherein said crystalline form contains no more than about 10% of any other form of Tiotropium bromide. 
     
     
         154 . The Tiotropium bromide of  claim 153 , wherein said any other form of Tiotropium bromide is form 3. 
     
     
         155 . Crystalline Tiotropium bromide, characterized by a powder XRD pattern having peaks at about 19.1, 20.2, 26.5, 28.0, and 31.2±0.2 degrees 2-theta, or by a powder X-ray diffractogram as depicted in  FIG. 12 , wherein said crystalline form contains no more than about 5% of any other form of Tiotropium bromide. 
     
     
         156 . The Tiotropium bromide of  claim 155 , wherein said any other form of Tiotropium bromide is form 3. 
     
     
         157 . The crystalline tiotropium bromide of  claim 75 , further characterized by a powder X-ray diffractogram as depicted in  FIG. 12 .