Abstract Nowadays, pharmaceutical cocrystals are an alternative approach to the synthesis of new solids without altering active pharmaceutical ingredients of the drug. In this study, lamotrigine (LTG) theophylline (THP) cocrystal monohydrate (1:1:1) and LTG glutarimide (GLU) cocrystal (1:1) were synthesized and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and Fourier transform infrared analysis. The Hirshfeld surface and 2D fingerprint of the LTG molecule in LTG-THP-H2O and LTG-GLU indicated that the main intermolecular forces between two LTG cocrystals molecules are H•••N/N•••H and H•••O. Dissolution results and stability studies demonstrated that the properties of LTG were enhanced by cocrystal formation. Contrary to LTG-GLU, LTG-THP-H2O posed slower dissolution rate and higher stability capability, which can be ascribed to the hydrated structure in LTG-THP-H2O and the aminopyridine dimer structure in LTG-GLU. Hence, it is necessary to select the conformers purposefully as to improve the corresponding performance of LTG.

中文翻译：

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拉莫三嗪共晶晶体结构与理化性质的关系

摘要 如今，药物共晶是一种在不改变药物活性成分的情况下合成新固体的替代方法。本研究合成了拉莫三嗪 (LTG) 茶碱 (THP) 共晶一水合物 (1:1:1) 和 LTG 戊二酰亚胺 (GLU) 共晶 (1:1)，并通过单晶 X 射线衍射、粉末 X 射线表征衍射和傅里叶变换红外分析。LTG-THP-H2O和LTG-GLU中LTG分子的Hirshfeld表面和二维指纹表明，两个LTG共晶分子之间的主要分子间作用力为H•••N/N•••H和H•••O。溶解结果和稳定性研究表明，LTG 的性质通过共晶形成得到增强。与 LTG-GLU 不同，LTG-THP-H2O 具有更慢的溶解速度和更高的稳定性，这可以归因于 LTG-THP-H2O 中的水合结构和 LTG-GLU 中的氨基吡啶二聚体结构。因此，有必要有目的地选择构象异构体以提高LTG的相应性能。