Bates Simon, Kelly Ron C, Ivanisevic Igor, Schields Paul, Zografi George, Newman Ann W
SSCI, Inc., West Lafayette, Indiana 47906, USA.
J Pharm Sci. 2007 May;96(5):1418-33. doi: 10.1002/jps.20944.
The progressive conversion of crystalline raffinose pentahydrate to its amorphous form by dehydration at 60 degrees C, well below its melting temperature, was monitored by X-ray powder diffraction over a period of 72 h. The presence of defects within the crystal structure and any amorphous structure created was determined computationally by a total diffraction method where both coherent long-range crystalline order and incoherent short-range disorder components were modeled as a single system. The data were analyzed using Rietveld, pair distribution function (PDF), and Debye total diffraction methods. Throughout the dehydration process, when crystalline material was observed, the average long-range crystal structure remained isostructural with the original pentahydrate material. Although the space group symmetry remained unchanged by dehydration, the c-axis of the crystal unit cell exhibited an abrupt discontinuity after approximately 2 h of drying (loss of one to two water molecules). Analysis of diffuse X-ray scattering revealed an initial rapid build up of defects during the first 0.5 h with no evidence of any amorphous material. From 1-2 h of drying out to 8 h where the crystalline structure is last observed, the diffuse scattering has both amorphous and defect contributions. After 24 h of drying, there was no evidence of any crystalline material remaining. It is concluded that the removal of the first two waters from raffinose pentahydrate created defects, likely in the form of vacancies, that provided the thermodynamic driving force and disorder for subsequent conversion to the completely amorphous state.
通过在60摄氏度（远低于其熔点）下脱水，将结晶性五水棉子糖逐步转化为其无定形形式，并在72小时内通过X射线粉末衍射进行监测。通过一种全衍射方法以计算方式确定晶体结构内的缺陷以及所形成的任何无定形结构，其中相干的长程晶体有序和非相干的短程无序成分被建模为一个单一系统。使用Rietveld、对分布函数（PDF）和德拜全衍射方法对数据进行分析。在整个脱水过程中，当观察到结晶材料时，平均长程晶体结构与原始五水合物材料保持同构。尽管脱水后空间群对称性保持不变，但晶体晶胞的c轴在干燥约2小时后（失去一到两个水分子）出现突然的不连续性。对漫散射X射线的分析表明，在最初的0.5小时内缺陷迅速积累，没有任何无定形材料的迹象。从干燥1 - 2小时到最后观察到晶体结构的8小时，漫散射既有无定形成分又有缺陷成分。干燥24小时后，没有任何结晶材料残留的迹象。得出的结论是，从五水棉子糖中去除前两个水分子会产生缺陷，可能以空位的形式存在，这为随后转化为完全无定形状态提供了热力学驱动力和无序性。
