Characterization of the polymorphic behavior of an organic compound using a dynamic thermal and X-ray powder diffraction technique

The crystalline polymorphic forms of several samples of an organic compound produced by Dowpharma were characterized using differential scanning calorimetry (DSC); X-ray powder diffraction (XRPD); combined, simultaneous, and dynamic differential scanning calorimetry/X-ray powder diffraction (DSC/XRPD); and high performance liquid chromatography (HPLC). A total of 10 crystalline polymorphs were identified, six of which are anhydrous. Form I is a heptahydrate that reversibly converts to anhydrous Form I under dry conditions and also undergoes a reversible solid-solid phase transition at about 110 degrees C to convert to Form H. Form Il is anhydrous and melts at approximately 220 degrees C. Form III crystallizes as a hexahydrate, which reversibly converts to the monohydrate Form III and then to an anhydrous Form III above 120 degrees C. Anhydrous Form III melts at approximately 200 degrees C. Form IN crystallized as a hydrous material, which was converted to the anhydrous Form IN above approximately 60 degrees C, in a reversible process. Form W appears to be unstable in high humidity conditions (e.g., 90% relative humidity at 25 degrees C and slowly converts to Forms I and III. Form IN also undergoes a nonreversible solid-solid, phase transition at approximately 180 degrees C, to form anhydrous Form V. Form V melts at approximately 245 degrees C. Form VI is observed only in the anhydrous state and melts at approximately 245 degrees C. The anhydrous nature of Form VI makes this material the most ideal crystalline material for subsequent formulation work.