Drug–Drug Multicomponent Crystals of Epalrestat: A Novel Form of the Drug Combination and Improved Solubility and Photostability of Epalrestat

In this work, three novel drug–drug multicomponent crystals containing two drugs to treat diabetes, epalrestat (EP) and edaravone (ED) or pregabalin (PR), namely, EP-ED cocrystal, EP–-PR-H+ salt-cocrystal monohydrate, and the dehydrate EP-PR, were successfully synthesized. The purpose is to improve the low solubility and photostability of EP and simultaneously achieve the synergistic effect of the drugs, which may enhance the therapeutic effect of diabetic peripheral neuropathy. As expected, the drug–drug multicomponent crystals exhibit better physicochemical properties. The enhanced photostability can be attributable to the alleviated Z,Z-isomerization of EP and the abundant interactions (mainly hydrogen bonds) inside the EP-PR multicomponent crystals. Moreover, the solubility and dissolution rate become better since ED or PR with better solubility participates in the crystal structure arrangement of multicomponent crystals. We believe that the drug–drug multicomponent crystals of EP and ED or PR have potential applications in the treatment of diabetic peripheral neuropathy owing to the improved physicochemical properties and the drug synergistic effect.