Salts and Cocrystals of Furosemide with Pyridines: Differences in π-Stacking and Color Polymorphism

Abstract

Furosemide (FS), a loop diuretic drug, exhibits polymorphism not only in pure entity, but also in cocrystal/salt forms. In continuation of our previous report of color cocrystals polymorphism of FS and 4,4′-bipyridine (4BPY), FS was further screened for color cocrystals by cocrystallization with other pyridines using a slow evaporative solution crystallization method. Interestingly, 2:1 molecular salt of FS and 1,2-bis(4-pyridyl)ethylene (4BPE) displayed color polymorphism in isopropanol yielding an orange (form 1I, plates) and the yellow (form 1II, blocks) crystals concomitantly. The yield of orange crystals, which appeared within 10–15 h, has always been more compared to the later formed yellow crystals, thus signifying the preference for orange crystals. The cocrystallization experiment once also yielded a yellow-colored 2:3 molecular salt (form 1III); however these crystals could not be reproduced later. Further, cocrystallization of FS and 4BPE from THF, dioxane, and their mixture produced comparativ...