Ahlqvist Matti U A, Taylor Lynne S
Solid State Analysis, Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden.
J Pharm Sci. 2002 Mar;91(3):690-8. doi: 10.1002/jps.10068.
Water interacts with pharmaceutical materials in a number of different ways. The aim of this study was to investigate if exchange experiments with D(2)O can provide useful insights into the structure of hydrated materials. Raffinose pentahydrate, trehalose dihydrate, and sucrose were used as model compounds in conjunction with their amorphous counterparts. Following exposure to D(2)O vapor, the exchange of water of hydration and/or hydroxyl groups was monitored using Raman spectroscopy. For the amorphous materials, all of the sugar hydroxyl groups were found to exchange on exposure to D(2)O, providing evidence that water has no fixed site in amorphous materials, nor is access to different parts of the molecule restricted. For raffinose pentahydrate and trehalose dihydrate, exchange of both hydrate water and hydroxyls was incomplete, suggesting that there are specific pathways for diffusion into and within the crystal structure. The results are rationalized based on the known crystal structures. Using exchange experiments to investigate hydrates thus appears to be a useful probe of structure.
水以多种不同方式与药物材料相互作用。本研究的目的是调查用重水（D₂O）进行交换实验是否能为水合材料的结构提供有用的见解。棉子糖五水合物、海藻糖二水合物和蔗糖与其无定形对应物一起用作模型化合物。暴露于重水蒸汽后，使用拉曼光谱监测水合水和/或羟基的交换。对于无定形材料，发现所有糖羟基在暴露于重水时都会发生交换，这表明水在无定形材料中没有固定位置，分子不同部分的可达性也不受限制。对于棉子糖五水合物和海藻糖二水合物，水合水和羟基的交换都不完全，这表明存在扩散进入晶体结构和在晶体结构内扩散的特定途径。根据已知的晶体结构对结果进行了合理化解释。因此，利用交换实验研究水合物似乎是一种有用的结构探测方法。
