Epalrestat-Cytosine Cocrystal and Salt Structures: Attempt to Control E,Z → Z,Z Isomerization

Abstract

Cocrystallization of the antidiabetic drug Eparlestat (EPR) with cytosine (CYT) gave EPR--CYT-H+ form I, a salt-cocrystal hybrid structure, salt hydrate (EPR--CYT-H+-H2O, 1:2:1), and nonstoichiometric solvates of EPR--CYT-H+ with EtOH/n-PrOH included in the rhombohedral symmetry voids, referred to as form II. Desolvation of EPR--CYT-H+ form II solvates resulted in an unsolvated form II of EPR--CYT-H+ which was characterized by DSC, TGA, and NMR. The carboxylate···cytosinium synthon was observed in the salt structure along with the uncommon CYT-H+···H+-CYT base pairing in the structures of salt-cocrystal hybrid and salt hydrate. The crystalline forms were characterized by spectroscopic (IR, NMR), thermal (DSC, HSM, TGA), powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SC-XRD) techniques. The intent of using the salt/salt-cocrystal forms as a means to stop the E,Z → Z,Z isomerization of EPR was not successful in photoirradiation experiments.