Three different hydrates of LB30870, a new direct thrombin inhibitor, were identified during the screening of solid form, and their interconversion relationship and relative thermodynamic stabilities were investigated. Form I (hexahydrate) changes to Form II (dihydrate) or Form III (tetrahydrate) by dehydration, while Form II becomes Form I by hydration, and both Form II and Form III change to Form I in the aqueous slurry. Single crystals obtained from two different crystallization conditions, wet or air-dried, were found to be isostructural with a difference in the solvent channels, and based on the simulated and experimental powder X-ray diffraction patterns, the air-dried crystals are assigned as Form I and Form III, respectively. In all crystal structures, LB30870 is in a folded conformation forced by the presence of strong hydrogen bonds by two structural water molecules. The solvent channel formed can hold up to six additional hydration water sites per each LB30870, and the one-dimensional solvent channel facilitates the interconversion among the hydrates and rapid conversion to Form I in water. Although all hydrate forms would not differ in oral bioavailability as Form I predominates in the aqueous phase, considering the stable water content at 40–75% relative humidity Form III would be the most suitable for further development.

中文翻译：

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LB30870，一种直接凝血酶抑制剂的伪多晶型物：一维溶剂通道结构说明可逆的水合/脱水

固体形式的筛选过程中，确定了一种新的直接凝血酶抑制剂LB30870的三种不同水合物，并研究了它们的相互转化关系和相对热力学稳定性。形式I（六水合物）通过脱水变为形式II（二水合物）或形式III（四水合物），而形式II通过水合变为形式I，并且形式II和形式III都在水性浆料中变为形式I。发现从两种不同的结晶条件（湿法或风干）获得的单晶具有相同的结构，溶剂通道不同，并且根据模拟和实验粉末X射线衍射图，将风干晶体指定为表格I和表格III。在所有晶体结构中 LB30870处于折叠状态，这是由于两个结构水分子存在强氢键而导致的。每个LB30870形成的溶剂通道最多可容纳六个额外的水合水位，并且一维溶剂通道可促进水合物之间的相互转化以及在水中快速转化为I型。尽管所有形式的水合物在口服生物利用度方面均无差异，因为形式I主要存在于水相中，但考虑到相对湿度为40-75％的稳定水含量，形式III最适合进一步开发。