Yonemochi E, Inoue Y, Buckton G, Moffat A, Oguchi T, Yamamoto K
Centre for Materials Science, School of Pharmacy, University of London, UK.
Pharm Res. 1999 Jun;16(6):835-40. doi: 10.1023/a:1018817801444.
To study the crystallization of ground and quenched ursodeoxycholic acid (UDCA) and to characterize their amorphous states.
Amorphous UDCA was prepared by grinding and also by rapid cooling of the melt. These samples were characterized by powder X-ray diffraction (XRD), near IR spectra and dynamic water sorption. The heat associated with crystallization was measured in an isothermal microcalorimeter at 25 degrees C at various relative humidities (RH) (50%-100%) and, in the presence of the vapour from a mixed solvent of ethanol and water (ethanol conc. 10%-100%). The specific surface area was calculated from krypton adsorption. Contact angles were measured by using a Wilhelmy plate to calculate the surface energy of the samples.
Ground and quenched samples yielded amorphous XRD patterns. Differential scanning calorimetry thermographs of the milled sample revealed that crystallization occurred at around 80 degrees C, whereas the quenched sample did not crystallize. Exposure to humid air did not result in crystallization of either amorphous sample during the microcalorimetric experiments. In the presence of ethanol vapour, the ground sample did, but the quenched sample did not, crystallize. The amount of water sorption into the quenched sample was larger than that of the ground sample at low RH. The surface energy of the quenched material was different to that of the ground. Peak shifts were observed in the NIR spectra at around 1450, 2100 nm, allowing differentiation between the ground and quenched samples.
It can be concluded that different molecular states of amorphous UDCA were obtained depending on the preparation method. The crystallisation of amorphous UDCA was related to the molecular state of disorder.
研究研磨和骤冷熊去氧胆酸（UDCA）的结晶情况，并对其非晶态进行表征。
通过研磨以及熔体快速冷却制备非晶态UDCA。这些样品通过粉末X射线衍射（XRD）、近红外光谱和动态水吸附进行表征。在25℃下，于不同相对湿度（RH）（50%-100%）以及存在乙醇和水的混合溶剂（乙醇浓度10%-100%）的蒸汽条件下，使用等温微量热计测量与结晶相关的热量。通过氪吸附计算比表面积。使用Wilhelmy板测量接触角以计算样品的表面能。
研磨和骤冷样品呈现非晶态XRD图谱。研磨样品的差示扫描量热法热谱图显示结晶在约80℃发生，而骤冷样品未结晶。在微量热实验期间，暴露于潮湿空气中未导致任何一种非晶态样品结晶。在存在乙醇蒸汽的情况下，研磨样品结晶了，但骤冷样品未结晶。在低RH下，骤冷样品的吸水量大于研磨样品。骤冷材料的表面能与研磨材料不同。在近红外光谱中，在约1450、2100nm处观察到峰位移，可区分研磨和骤冷样品。
可以得出结论，根据制备方法可获得非晶态UDCA的不同分子状态。非晶态UDCA的结晶与无序分子状态有关。
