Yonemochi E, Ueno Y, Ohmae T, Oguchi T, Nakajima S, Yamamoto K
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Pharm Res. 1997 Jun;14(6):798-803. doi: 10.1023/a:1012114825513.
The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the thermal methods (microcalorimetry and differential scanning calorimetry (DSC) for studying the amorphous state and clarifying the dissolution mechanism of UDCA.
Amorphous UDCA was prepared by grinding and rapid cooling of the melts. The heat of solution of UDCA was measured by an isothermal heat-conduction twin microcalorimeter at 25.0 degrees C. Some physicochemical properties of amorphous UDCA were also studied.
The intensities of X-ray diffraction peaks of crystalline UDCA decreased with an increase in grinding time. The heat levels of solution of crystalline UDCA and UDCA ground for 1 min were endothermic, and became exothermic with an increase in grinding time. A good correlation was obtained between the heat of solution and the heat of crystallization determined from the peak area in DSC. Although no significant difference was observed in X-ray diffraction patterns of amorphous UDCA prepared by the two methods, significant differences were recognized in DSC, IR and 13C-NMR, and the heat of solution indicated different values among the two samples. The stability of amorphous UDCA samples stored under 74.5% relative humidity at 40 degrees C was found to depend upon the preparation methods.
Different states of amorphous UDCA were obtained depending on the preparation method. The application of thermal methods to evaluate the amorphous state was demonstrated. The mechanism of dissolution of UDCA was discussed from the results of the heat of solution examination.
本研究旨在通过等温微量热法、X射线衍射、红外（IR）光谱和固态碳13核磁共振（13C-NMR）光谱对熊去氧胆酸（UDCA）样品的非晶态进行表征，并证明热分析方法（微量热法和差示扫描量热法（DSC））在研究UDCA非晶态及阐明其溶解机制方面的应用。
通过研磨和熔体快速冷却制备非晶态UDCA。在25.0℃下用等温热传导双微量热计测量UDCA的溶解热。还研究了非晶态UDCA的一些物理化学性质。
结晶态UDCA的X射线衍射峰强度随研磨时间的增加而降低。结晶态UDCA和研磨1分钟的UDCA的溶解热水平为吸热，随着研磨时间的增加变为放热。溶解热与通过DSC峰面积测定的结晶热之间具有良好的相关性。虽然通过两种方法制备的非晶态UDCA的X射线衍射图谱未观察到显著差异，但在DSC、IR和13C-NMR中观察到显著差异，并且两个样品的溶解热显示出不同的值。发现在40℃、相对湿度74.5%条件下储存的非晶态UDCA样品的稳定性取决于制备方法。
根据制备方法可获得不同状态的非晶态UDCA。证明了热分析方法在评估非晶态方面的应用。从溶解热检查结果讨论了UDCA的溶解机制。
