Ueno Y, Yonemochi E, Tozuka Y, Yamamura S, Oguchi T, Yamamoto K
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
J Pharm Pharmacol. 1998 Nov;50(11):1213-9. doi: 10.1111/j.2042-7158.1998.tb03336.x.
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.
本研究的目的是表征通过喷雾干燥制备的熊去氧胆酸（UDCA）样品的非晶态，并证明热分析和水蒸气吸附技术在研究该材料方面的适用性。通过将该化合物在乙醇和二氯甲烷的混合物中的溶液进行喷雾干燥来制备非晶态UDCA。采用粉末X射线衍射、红外（IR）光谱、等温微量热法、差示扫描量热法（DSC）和水蒸气吸附对非晶态材料进行表征。当喷雾干燥器的进气温度升高到140℃以上时，结晶态UDCA的X射线衍射峰强度降低，羟基伸缩和羧基伸缩区域的IR谱带发生变化。在60℃和100℃下制备的完整和喷雾干燥的UDCA样品的溶解是一个吸热过程，但随着进气温度的升高，溶解变为放热过程。根据进气温度的不同，获得了结晶度不同的UDCA样品。由DSC峰面积确定的溶解热与结晶热之间具有良好的相关性。由X射线衍射图谱通过鲁兰德方法确定的溶解热与结晶度之间也具有良好的相关性。UDCA样品上吸附的水蒸气量随进气温度的升高而增加，表明水分子与非晶态UDCA的羟基或羧基之间存在氢键。这些结果表明，水蒸气吸附测量和热分析均可用于评估固体物质的结晶度。
