化学
拉莫三嗪
差示扫描量热法
噻唑
共晶
红外光谱学
互变异构体
茶碱
结晶学
立体化学
分子
物理化学
有机化学
氢键
热力学
内分泌学
物理
神经科学
癫痫
生物
医学
作者
António O. L. Évora,Ricardo A. E. Castro,Teresa M. R. Maria,Manuela Ramos Silva,João Canotilho,M. Ermelinda S. Eusébio
标识
DOI:10.1016/j.ejps.2019.01.007
摘要
In this work, a crystal engineering and thermodynamic based approach has been used aiming at contributing to a deeper knowledge of lamotrigine multicomponent solid forms. Two types of co-molecules have been chosen that can give rise to co-crystals with lamotrigine through different supramolecular heterosynthons: the xanthines, theophylline and caffeine, and the three isomeric pyridinecarboxamides. Association with diflunisal, which may result in a salt, was also investigated. Mechanochemistry, differential scanning calorimetry, thermogravimetry, X-ray powder and single crystal diffraction, infrared spectroscopy were the methods used. For all the systems, exploratory neat mechanochemistry experiments, carried out on lamotrigine + co-molecule binary mixtures of different compositions, were not successful in promoting association. From differential scanning calorimetry data and the binary solid-liquid phase diagrams, co-crystals/salts were identified as well as their respective stoichiometry, and a methodology of synthesis was established. For pyridinecarboxamides, molecular recognition is dependent on the position of the amide group in the pyridine ring: co-crystallization did not occur with picolinamide co-former. Both xanthines form co-crystals with lamotrigine, (1:1) with theophylline and (2:1) lamotrigine:caffeine. Additionally, the crystalline structure of a lamotrigine:theophylline 1:1 monohydrate was solved. The (1:1) lamotrigine:theophylline co-crystal converts to this monohydrate in accelerated stability tests. A (1:1) lamotrigine:diflunisal salt was identified, which proved to be stable in accelerated stability assays.
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