PREPARATION OF PIRETANIDE POLYMORPHS AND THEIR PHYSICOCHEMICAL PROPERTIES AND DISSOLUTION BEHAVIORS

Piretanide polymorphs were prepared by recrystallization using 27 orga nic solvents. We identified a new polymorphism forms A and B, and 6 so lvates. They were characterized by X-ray ponder diffractometry, differ ential scanning calorimetry (DSC), thermogravimetry (TG), Fourier-tran sform infrared (FTIR) spectroscopy, elemental analysis and scanning el ectron microscopy. After heating, some solvates transformed to the sta ble form A, and others to form B. X-ray ponder diffraction patterns an d FTIR spectra of forms A and B were significantly different. However, the X-ray powder diffraction patterns acid FTIR spectra of form A and the bulk sample were similar. The DSC curve of form A showed only an endothermic peak at 227 degrees C corresponding to the melting point. The DSC curve of form B showed endothermic and exothermic peaks at 213 and 216 degrees C, respectively, as well as a subsequent endothermic peak at 227 degrees C. The metastable form B transformed to form A. Th e dissolution profiles of the bulk sample and form B in JP XII, 1st fl uid (pH 1.2) at 37 degrees C were measured by means of the dispersed a mount. The solubilities of the bulk sample and form B were estimated t o be 8.3 and 13.3 mg/100 ml, respectively.