Wildfong Peter L D, Morris Kenneth R, Anderson Carl A, Short Steven M
Duquesne University Mylan School of Pharmacy, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA.
J Pharm Sci. 2007 May;96(5):1100-13. doi: 10.1002/jps.20920.
Elucidation of the mechanisms for mechanically activated phase transformations of API are necessary for progress in materials and process understanding. The mechanically induced solid-state transformation between the A and C enantiotropes of the anti-diabetic drug chlorpropamide (C(10)H(13)ClN(2)O(3)S) was investigated. The structure of the high temperature stable phase (form C) was solved using powder X-ray data. Transmission powder X-ray diffraction (PXRD) and Raman spectroscopy were used for in situ quantification and analysis of the phase interconversion that occurs as a function of applied pressure during compaction. Each polymorph was observed to undergo a solid-state transition, which increased with pressure to a maximum extent that corresponded with the consolidation limit of the respective bulk powder. Neither form was observed to convert under hydrostatic pressure, suggesting a shear dependence for interconversion at compaction pressures. Examination of the two crystallographic structures indicated that both forms have a common slip system and preserved molecular positions. It is suggested that the transformation of either form is allowed when resolved shear stresses initiate deformation, causing lattice distortion, which allows the simultaneous reconformation of molecules.
阐明药物活性成分机械激活相变的机制对于材料和工艺理解的进展至关重要。研究了抗糖尿病药物氯磺丙脲（C(10)H(13)ClN(2)O(3)S）的A和C对映变体之间的机械诱导固态转变。利用粉末X射线数据解析了高温稳定相（晶型C）的结构。采用透射粉末X射线衍射（PXRD）和拉曼光谱对压实过程中随施加压力而发生的相转变进行原位定量和分析。观察到每种多晶型物都经历了固态转变，该转变随压力增加到最大程度，这与各自散装粉末的固结极限相对应。在静水压力下未观察到任何一种晶型发生转变，这表明在压实压力下转变存在剪切依赖性。对两种晶体结构的研究表明，两种晶型都有一个共同的滑移系统且分子位置保持不变。有人认为，当分解剪应力引发变形导致晶格畸变，从而使分子能够同时重新构象时，任何一种晶型的转变都是可能的。
