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On the track of new multicomponent gabapentin crystal forms: Synthon competition and pH stability

机译:新型多组分加巴喷丁晶体形式的发展轨迹:Synthon竞争和pH稳定性

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摘要

Five new multicomponent crystal forms of the neuroleptic drug gabapentin with isophthalic acid, phthalic acid, l-glutamine, and terephthalic and trimesic acids have been reported and are characterized by XRPD. While the single crystal structures of the first three compounds were not possible to determine, the latter two are further characterized by SCXRD, DSC, TGA, HSM, and IR. The strong homomeric R_2~2(8) and heteromeric R_4~2(8) synthons observed in the carboxylic acids and gabapentin, respectively, were disrupted and competing synthons based on carboxyl???carboxylate and amine???carboxylate interactions formed in the new crystalline structures with trimesic and terephthalic acids. The pH dependent stability of these two new forms was also studied, and significant differences were found for the cocrystal with trimesic acid and the molecular salt with terephthalic acid, which is stable in quite a narrower pH range. Furthermore, mechanochemistry proved to be an advantageous alternative to traditional solution techniques when highly insoluble compounds are under study.
机译:已经报道了抗精神病药加巴喷丁的五种新的多组分晶体形式,其中包括间苯二甲酸,邻苯二甲酸,1-谷氨酰胺,对苯二甲酸和偏苯三酸,并用XRPD表征。尽管前三种化合物的单晶结构无法确定,但后两种化合物的特征还在于SCXRD,DSC,TGA,HSM和IR。分别在羧酸和加巴喷丁中观察到的强同聚R_2〜2(8)和异聚R_4〜2(8)合成子被破坏,并且基于在羧酸和加巴喷丁中形成的羧基,羧基和胺基的相互作用形成竞争性合成子。均苯三酸和对苯二甲酸的新晶体结构。还研究了这两种新形式的pH依赖性稳定性,发现与偏苯三酸的共晶和与对苯二甲酸的分子盐的显着差异,它们在相当窄的pH范围内是稳定的。此外,当正在研究高度不溶的化合物时,机械化学被证明是传统溶液技术的有利替代品。

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