Characterization of amorphous ursodeoxycholic acid prepared by spray-drying.
The objectives of this study were to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples prepared by spray-drying, and to demonstrate 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 characterized 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 crystalline UDCA decreased and the IR bands in the hydroxyl-stretching and carboxyl-stretching regions changed. Dissolution of intact and spray-dried samples of UDCA prepared at 60 and 100 degrees C was an endothermic process but the dissolution became exothermic with increasing inlet-air temperature. UDCA samples differing in crystallinity were obtained, depending on the inlet-air temperature. A good correlation was obtained between the heat of solution and the heat of crystallization determined from DSC peak area. A good correlation was also obtained between the heat of solution and the crystallinity determined by Ruland's method from X-ray diffraction patterns. The amount of water vapour adsorbed on UDCA samples increased with increasing inlet-air temperature, indicating hydrogen bonding between water molecules and the hydroxyl groups or the carboxyl groups of amorphous UDCA. These results indicate that measurement of adsorption of water vapour and thermal analysis can both be used to evaluate the crystallinity of solid substances.
Ueno
Y
Y
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yonemochi
E
E
Tozuka
Y
Y
Yamamura
S
S
Oguchi
T
T
Yamamoto
K
K
D000327:Adsorption; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D003461:Crystallography; D004055:Differential Thermal Analysis; D020073:Gravidity; D013055:Spectrophotometry, Infrared; D013696:Temperature; D014580:Ursodeoxycholic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction
D014580:Ursodeoxycholic Acid