Characterization of amorphous ursodeoxycholic acid prepared by spray-drying

The objectives of this study were to characterize the amorphous state of ur sodeoxycholic acid (UDCA) samples prepared by spray-drying, and to demonstr ate the applicability of thermal and water-vapour-adsorption techniques for studying the material. Amorphous UDCA was prepared by spray-drying a solution of the compound in a mixture of ethanol and dichloromethane. The amorphous material was charact erized by powder X-ray diffraction, infrared (IR) spectroscopy, isothermal microcalorimetry, differential scanning calorimetry (DSC) and water-vapour adsorption. When the inlet-air temperature of the spray drier was increased beyond 140 degrees C, the intensity of X-ray diffraction peaks from crysta lline UDCA decreased and the IR bands in the hydroxyl-stretching and carbox yl-stretching regions changed. Dissolution of intact and spray-dried sample s of UDCA prepared at 60 and 100 degrees C was an endothermic process but t he dissolution became exothermic with increasing inlet-air temperature. UDC A samples differing in crystallinity were obtained, depending on the inlet- air temperature. A good correlation was obtained between the heat of soluti on and the heat of crystallization determined from DSC peak area. A good co rrelation was also obtained between the heat of solution and the crystallin ity determined by Ruland's method from X-ray diffraction patterns. The amou nt of water vapour adsorbed on UDCA samples increased with increasing inlet -air temperature, indicating hydrogen bonding between water molecules and t he hydroxyl groups or the carboxyl groups of amorphous UDCA. These results indicate that measurement of adsorption of water vapour and t hermal analysis can both be used to evaluate the crystallinity of solid sub stances.