Epalrestat–Cytosine Cocrystal and Salt Structures: Attempt To Control E,Z → Z,Z Isomerization

• Published in: Crystal growth & design 2017-06, Vol.17 (6), p.3350-3360
• Main Authors: Swapna, Battini, Nangia, Ashwini
• Format: Article
• Language: English
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/acs.cgd.7b00322

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.