XtalPi Inc. 245 Main St, 11th Floor, Cambridge, MA, 02142, USA.
Merck KGaA, Frankfurter Straße 250, 64293, Darmstadt, Germany.
Small Methods. 2023 Jun;7(6):e2201692. doi: 10.1002/smtd.202201692. Epub 2023 Mar 25.
The crystal habit can have a profound influence on the physical properties of crystalline materials, and thus controlling the crystal morphology is of great practical relevance across many industries. Herein, this work investigates the effect of polymer additives on the crystal habit of metformin HCl with both experiments and computational methods with the aim of developing a combined screening approach for crystal morphology engineering. Crystallization experiments of metformin HCl are conducted in methanol and in an isopropanol-water mixture (8:2 V/V). Polyethylene glycol, polyvinylpyrrolidone, Tween80, and hydroxypropyl methylcellulose polymer additives are used in low concentrations (1-2% w/w) in the experiments to study the effect they have on modifying the crystal habit. Additionally, this work has developed computational methods to characterize the morphology "landscape" and quantifies the overall effect of solvent and additives on the predicted crystal habits. Further analysis of the molecular dynamics simulations is used to rationalize the effect of additives on specific crystal faces. This work demonstrates that the effects of additives on the crystal habit are a result of their absorption and interactions with the slow growing {100} and {020} faces.
晶体形态对结晶材料的物理性质有深远影响，因此控制晶体形态在许多行业都具有重要的实际意义。在此，本工作通过实验和计算方法研究了聚合物添加剂对盐酸二甲双胍晶体形态的影响，旨在开发一种用于晶体形貌工程的组合筛选方法。在甲醇和异丙醇-水混合物（8:2 V/V）中进行盐酸二甲双胍的结晶实验。实验中使用低浓度（1-2%w/w）的聚乙二醇、聚乙烯吡咯烷酮、吐温 80 和羟丙基甲基纤维素聚合物添加剂，研究它们对改变晶体形态的影响。此外，本工作还开发了计算方法来描述形态“景观”，并量化溶剂和添加剂对预测晶体形态的整体影响。进一步对分子动力学模拟进行分析，以合理推断添加剂对特定晶面的影响。本工作表明，添加剂对晶体形态的影响是其与生长缓慢的{100}和{020}面的吸附和相互作用的结果。
