Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques
Physicochemical Understanding of Polymorphism and Solid-State Dehydration/Rehydration Processes for the Pharmaceutical Material Acrinol, by Ab Initio Powder X-ray Diffraction Analysis and Other Techniques
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DOI：
10.1021/jp908636t
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发表时间：
2010-01-14
影响因子：
3.7
通讯作者：
Harris, Kenneth D. M.
中科院分区：
文献类型：
--
作者：
Fujii, Kotaro;Uekusa, Hidehiro;Harris, Kenneth D. M.
广泛使用的抗菌剂acrinol 已知会在从水中结晶时形成一水合物相(H)。我们在此证明，acrinol 还形成两种无水多晶型物，表示为 I 型 (AI) 和 II 型 (AII)。多晶型AI是通过固态脱水过程在加热H时直接获得的，而多晶型All是随后通过多晶型转化从AI获得的。 AI和AII的晶体结构是直接根据粉末X射线衍射数据确定的，采用直接空间遗传算法技术进行结构求解，然后进行Rietveld精修。根据AI和AII的结构特性，脱水过程和多晶型转化的机制已经建立。根据初始溶解速率和溶解焓的测量，AII 被指定为热力学稳定的多晶型物，AI 和 AII 之间具有单变性关系。 AI 和 AII 的水化特性显着不同，AI 的水化发生在比 AII 低得多的相对湿度下。
The extensively used antibacterial agent acrinol is known to form a monohydrate phase (H) on crystallization from water. We demonstrate here that acrinol also forms two anhydrous polymorphs, denoted form I (AI) and form II (AII). Polymorph AI is obtained directly on heating H, by a solid-state dehydration process, and polymorph All is obtained subsequently from AI, by a polymorphic transformation. The crystal structures of AI and AII have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. From the structural properties of AI and AII, mechanistic aspects of the dehydration process and the polymorphic transformation have been established. From measurements of initial dissolution rates and enthalpies of dissolution, AII is assigned as the thermodynamically stable polymorph, with a monotropic relationship between AI and AII. The hydration properties of AI and AII differ significantly, with hydration of AI occurring at substantially lower relative humidity than AII.