文献类型：期刊文献

英文题名：Computational study of metformin hydrochloride nucleation in hydroxylic solvents: Experimental kinetics and DFT simulation

作者：Gu, Xing[1];Si, Zehao[1];Yan, Yizhen[1];Zhang, Xiangyang[1]

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

年份：2022

卷号：616

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000781104100005)】；

基金：This work was financially supported by the National Natural Science Foundation of China (NSFC, No.22078093) and Ningxia Beilite Chemi-cal Industry Co., Ltd.

语种：英文

外文关键词：Metformin hydrochloride; Induction time; Metastable zone width; Nucleation; Binding energy

摘要：Metformin hydrochloride (MET-HCl) was applied as a model compound to investigate the nucleation behavior in four hydroxylic solvents based on the experimental and simulated methods. Over 320 induction time experi-ments were measured in four solvents, and the induction time increased in the order: water < methanol < ethanol < n-propanol. The metastable zone widths were determined with different cooling rates and saturation temperatures. According to classical nucleation theory, the nucleation kinetics and thermodynamic parameters (interfacial energy, critical nucleus size and Gibbs free energy) were estimated. The result indicates that the nucleation rate of MET-HCl in water was highest among four solvents. The density functional theory (DFT) calculation was applied to reveal the solvent-solute interaction in crystal nucleation, showing the binding en-ergies increased in the order: water < methanol < ethanol < n-propanol. The simulation results combined with experimental data suggested that the stronger the interactions of solvent-solute molecules, the more difficult the nucleation becomes.