文献类型：期刊文献

英文题名：A novel cocrystal of metformin hydrochloride with citric acid: Systematic synthesis and computational simulation

作者：Yan, Yizhen[1];Wang, Lijie[1];Si, Zehao[1];Zhang, Xiangyang[1];Yuan, Weikang[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China

年份：2022

卷号：179

起止页码：37

外文期刊名：EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000859665900003)】；

语种：英文

外文关键词：Cocrystal; Synthesis; Solubility; Binding energy; Hirshfeld surface

摘要：Pharmaceutical cocrystals have matured into an effective technique for tuning the physicochemical and me-chanical properties of drugs in solid form simultaneously. Herein, in order to provide a novel cocrystal form of oral medicine metformin hydrochloride (MH), citric acid (CA) was selected as an efficient ligand after screening a variety of inorganic and organic acids. Thus, based on the principle of crystal engineering, we report a novel cocrystal: metformin hydrochloride -citric acid (MHCA) after the systematic screening, which was experimen-tally proved to be constituted with 1:1 stoichiometry. Compared with pure MH, MHCA has been proved higher solubility in water, methanol, and ethanol from 283.15 to 313.15 K. Through single-crystal X-ray diffraction (SC-XRD), the particular molecular structure of MHCA has been determined as the orthorhombic system and Pbca space group. Besides, the binding model of MH-CA was built for investigating the binding energy and stability between two components at 278, 298, and 318 K, which were found to be essential for the prediction and analysis of cocrystals. The contribution of different intermolecular interactions and the strength of molecular packing in the cocrystal also have been investigated by Hirshfeld surface analysis. It was found that the cocrystal structure was mainly stabilized by intermolecular hydrogen bonds existing as N???H?????????O between components, which indicated that the diffusion-combination trend of molecules enhanced the regular array of cocrystal. The results revealed that the molecules of MH and CA formed supramolecular cocrystals mainly induced by hydrogen bonds after passive contacts, such as co-crystallization or grind. Superscript/Subscript Available