Amorphous form of a phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
View Patent ↗The present invention relates to a novel amorphous form of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I as well as a process for its preparation, pharmaceutical compositions containing this novel form, and methods of use of the novel form and pharmaceutical compositions for the treatment of diabetes, obesity, and high blood pressure.
1. An amorphous form of the dihydrogenphosphate salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I:
characterized by the X-ray powder diffraction pattern of FIG.1 .
2. The amorphous form of claim 1 characterized by a solid-state fluorine-19 magic-angle spinning (MAS) nuclear magnetic resonance spectrum showing signals at −63.7, −118.5, −136.6, and −143.3 p.p.m.
3. The amorphous form of claim 1 further characterized by the solid-state fluorine-19 magic-angle spinning (MAS) nuclear magnetic resonance spectrum of FIG. 3 .
4. The amorphous form of claim 1 characterized by a solid-state carbon-13 cross-polarization magic-angle spinning (CPMAS) nuclear magnetic resonance spectrum showing signals at 169.6, 150.6, 120.1, and 41.9 p.p.m.
5. The amorphous form of claim 4 further characterized by the solid-state carbon-13 cross-polarization magic-angle spinning (CPMAS) nuclear magnetic resonance spectrum of FIG. 2 .
6. The amorphous form of claim 1 characterized by the thermogravimetric analysis curve of FIG. 5 .
7. The amorphous form of claim 1 characterized by the differential scanning calorimetric (DSC) curve of FIG. 4 .
8. A pharmaceutical composition in solid form comprising a therapeutically effective amount of the amorphous form of claim 1 in association with one or more pharmaceutically acceptable carriers or excipients.