Understanding the polymorphic behavior of sibenadet hydrochloride through detailed studies integrating structural and dynamical assessment.
Understanding the polymorphic behavior of sibenadet hydrochloride through detailed studies integrating structural and dynamical assessment.
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通过结合结构和动力学评估的详细研究了解盐酸西贝那得的多晶型行为。
DOI：
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
K. Roberts
中科院分区：
文献类型：
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作者：
S. Cosgrove;G. Steele;T. Austin;A. Plumb;B. Stensland;E. Ferrari;K. Roberts
三种多晶型的西贝那得盐酸盐（AR-C68397 AA，Viozan）已被证明存在于环境温度下，并已进行了表征。每一种都经历了一个固态转变，变成一种常见的高温形式，在大约220摄氏度时熔化。X-射线粉末衍射（XRPD）表明多晶型物I和II共享多晶型物III未表现出的类似层状结构。所有三种环境温度多晶型物都显示出不同程度的末端苯基动态无序的证据，如固态NMR光谱所示。此外，醚键的α碳在多晶型物I和II中也经历不同的迁移率。这种动态无序程度的变化导致短程结构的改变，从而产生不同的多晶型物。多晶型物I在室温下是化学稳定的形式，如通过溶液量热法和化学驱动的溶液介导的相变研究的评估所指示的。本研究的目的是解决类型的歧视性数据需要作出明确区分的物理形式和定义，毫不含糊地，多态性的存在。
Three polymorphs of sibenadet hydrochloride (AR-C68397AA, Viozan) have been shown to exist at ambient temperature and have been characterized. Each undergoes a solid-state transition to a common high temperature form, which melts at approximately 220 degrees C. X-ray powder diffraction (XRPD) indicates that Polymorphs I and II share a similar layered structure not exhibited by Polymorph III. All three ambient temperature polymorphs show evidence of varying degrees of dynamic disorder of the terminal phenyl group as shown by solid-state NMR spectroscopy. Furthermore, the carbons alpha to the ether link also undergo different rates of mobility in Polymorphs I and II. This variation in the extent of dynamic disorder results in an alteration in the short-range structure resulting in distinct polymorphs. Polymorph I is the thermodynamically stable form at room temperature as indicated by solution calorimetry and assessment by thermodynamically driven solution mediated phase transition studies. The present study aims to address the types of discriminatory data required to make a clear distinction between physical forms and define, unequivocally, the presence of polymorphism.