Crystal forms of saxagliptin

Abstract

The present invention relates to novel polymorphic forms of Saxagliptin Hydrochloride. The present invention also relates to methods of making polymorphic forms of Saxagliptin Hydrochloride.

1 . Anhydrous crystalline forms of Saxagliptin hydrochloride having a water content of not more than 1.5% w/w. 
     
     
         2 . Saxagliptin hydrochloride according to  claim 1  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         3 . Crystalline Form I-S of Saxagliptin hydrochloride according to  claim 1  having a x-ray powder diffraction pattern comprising peaks at 6.7±0.2, 14.6±0.2, 15.2±0.2, 16.6±0.2 and 17.9±0.2 degrees two-theta and/or having an infrared spectrum comprising peaks at wavenumbers of 2907, 2853, 1637, 1589, 1462, 1391, 1318, 1045, 1014 and 775+/−2 cm −1 . 
     
     
         4 . Crystalline Form HT-S of Saxagliptin hydrochloride according to  claim 1  having a x-ray powder diffraction pattern comprising peaks at 6.6±0.2, 13.3±0.2 and 17.6±0.2 degrees two-theta and/or having an infrared spectrum comprising peaks at wavenumbers of 2906, 2854, 1649, 1574, 1513, 1459, 1338, 1124, 1032 and 851+/−2 cm −1 . 
     
     
         5 . Crystalline Form HT-IV-S of Saxagliptin hydrochloride according to  claim 1  having a x-ray powder diffraction pattern comprising peaks at 2.6, 4.5, 6.8, 14.6 and 18.1±0.2 degrees two-theta and/or having an infrared spectrum comprising peaks at wavenumbers of 3495, 2921, 1637, 1616, 1464, 1242, 1103, 1013, 940 and 774+/−2 cm −1 . 
     
     
         6 . Crystalline Form IV-S of Saxagliptin hydrochloride according to  claim 1  having an x-ray powder diffraction pattern comprising peaks at 2.4, 4.1, 4.7, 6.3 and 15.6±0.2 degrees two-theta. 
     
     
         7 . Pharmaceutical composition comprising an crystalline form of Saxagliptin according to  claim 1  in an effective amount. 
     
     
         8 . A process for the preparation of crystalline Saxagliptin hydrochloride Form I-S according to  claim 3  comprising the step of allowing Saxagliptin hydrochloride to crystallize from an alcohol in the presence of seed crystals of Saxagliptin hydrochloride Form I-S. 
     
     
         9 . A process for the preparation of crystalline Saxagliptin hydrochloride Form HT-S according to  claim 4  comprising the step of heating the known crystalline forms of Saxagliptin hydrochloride form H2-1, H1.25-2 or H.75-3 to about 160° C. to 180° C., and isolating Form HT-S. 
     
     
         10 . A method of using crystalline Saxagliptin hydrochloride according to  claim 1  alone or in combination with one or more types of antidiabetic agents and/or one or more other types of therapeutic agents which may be administered orally in the same dosage form for the preparation of a medicament in a separate dosage form or by injection. 
     
     
         11 . A pharmaceutical composition comprising crystalline Saxagliptin hydrochloride according to  claim 1 , wherein the equilibrium relative humidity of the composition is below 50%. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the equilibrium relative humidity of the composition is from 10% to 40%. 
     
     
         13 . A method of using Saxagliptin hydrochloride form IV-S according to  claim 6  for the preparation of Saxagliptin hydrochloride form HT-IV-S according to  claim 5 . 
     
     
         14 . The crystalline Form I-S of Saxagliptin hydrochloride according to  claim 3  having a x-ray powder diffraction pattern comprising peaks at 24.5±0.2 and 28.2±0.2 degrees two-theta. 
     
     
         15 . The crystalline Form HT-S of Saxagliptin hydrochloride according to  claim 4  having a x-ray powder diffraction pattern comprising peaks at 11.5±0.2 and 16.7±0.2 degrees two-theta. 
     
     
         16 . The crystalline Form HT-IV-S of Saxagliptin hydrochloride according to  claim 5  having a x-ray powder diffraction pattern comprising peaks at 2.6±0.2 and 6.8±0.2 two theta. 
     
     
         17 . The pharmaceutical composition according to  claim 7 , formulated for use in treating diabetes and/or related diseases.