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首页> 外文期刊>Crystal growth & design >Effect of the Counterion on the Solubility of Isostructural Pharmaceutical Lamotrigine Salts
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Effect of the Counterion on the Solubility of Isostructural Pharmaceutical Lamotrigine Salts

机译：抗衡离子对同构药物Lamotrigine盐溶解度的影响

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摘要

Salt formation is an approach to improve the physicochemical properties of the solid forms of an active pharmaceutical ingredient. As the anticonvulsant drug Lamotrigine presents low water solubility, a set of its salts with four different counterions has been obtained, and the influence of the counterion on the salt properties has been investigated. Lamotrigine salts have been obtained from succinic acid, fumaric acid, DL-tartaric acid, and saccharin. Powder samples of each salt have been characterized by infrared spectroscopy, powder X-ray diffraction, and thermal methods. Single crystal structures of four of these salts have been solved from single crystal X-ray diffraction data. The salts crystallized in P2(1)/c and P2(1) space groups, being isostructural dicarboxylic acid salts of lamotrigine. Crystal structures of these salts are built up by hydrogen bond interactions of type N(+)-H center dot center dot center dot O(-), N-H center dot center dot center dot O(-), O-H center dot center dot center dot N, and N-H center dot center dot center dot O. The water solubility of these salts has been determined and appears directly related to the solubility of the precursor acid. The isostructural nature of the studied salts allows connection of their properties with those of the counterion involved. The importance of the counterion solubility on the final solubility of the salts is rationalized considering their crystal structures.
机译：盐的形成是一种改善活性药物成分的固体形式的物理化学性质的方法。由于抗惊厥药拉莫三嗪的水溶性低，因此获得了一组带有四种不同抗衡离子的盐，并研究了抗衡离子对盐性质的影响。拉莫三嗪盐已从琥珀酸，富马酸，DL-酒石酸和糖精中获得。每种盐的粉末样品已通过红外光谱，粉末X射线衍射和热方法进行了表征。这些盐中的四种的单晶结构已经从单晶X射线衍射数据中解析出来。在P2（1）/ c和P2（1）/ n空间基团中结晶的盐是拉莫三嗪的同结构二羧酸盐。这些盐的晶体结构是由N（+）-H型中心点中心点中心点O（-），NH型中心点中心点中心点O（-），OH型中心点中心点中心点的氢键相互作用建立的N和NH中心点中心点中心点O。已经确定了这些盐的水溶性，并且看起来与前体酸的溶解度直接相关。研究的盐的同构性质允许其性质与所涉及的抗衡离子的性质相关。考虑到盐的晶体结构，抗衡离子溶解度对盐的最终溶解度的重要性是合理的。

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