Novel Drug–Drug Multicomponent Crystals of Epalrestat–Metformin: Improved Solubility and Photostability of Epalrestat and Reduced Hygroscopicity of Metformin
Jingjing Sun, Lina Jia, Mengwei Wang, Yu Liu, Min Li, Dandan Han, Junbo Gong
Abstract
In this study, we attempted to synthesize drug–drug multicomponent crystals containing epalrestat (EP) and metformin (MET) (two drugs both used for diabetes treatment) to improve the photostability and solubility of epalrestat and reduce the hygroscopicity of metformin. Four drug–drug multicomponent crystals were synthesized including EP––MET-H+ 1:1 (EP–MET), EP––MET-H+-acetone 1:1:1 (EP–MET SACE), EP––MET-H+-H2O 1:1:1 (EP–MET MH), and EP––MET–H+-ethanol-H2O 1:1:1:1 (EP–MET SETOH-H2O). Notably, we found that the strong hydrogen bonds between EP and MET molecules in the EP–MET SACE can prevent the transformation of the EP molecules from E, Z to Z, Z photoisomerization and further improve its photostability. Furthermore, the drug–drug multicomponent crystals exhibit stronger solubility and a higher dissolution rate than pure EP crystals and a lower hygroscopicity due to featuring a layered structure with alternately arranged EP and MET molecules.