In this study, we attempt to simultaneously improve the photostability and soly. of epalrestat (a drug used for neuropathy treatment) by prepg. epalrestat-betaine zwitterionic cocrystals and characterize the physicochem. property alterations accompanying their formation. Notably, we reveal that the strong hydrogen bonds between epalrestat and betaine mols. in the above cocrystals and the reduced size of the reaction cavity around epalrestat mols. prevent the E,Z to Z,Z photoisomerization of the latter, resulting in improved photostability. Furthermore, the prepd. cocrystals exhibit a higher soly. and larger dissoln. rate than pure epalrestat crystals due to featuring a layered structure with alternately arranged epalrestat and betaine coformer mols. [on SciFinder(R)]