Structural and physicochemical aspects of hydrochlorothiazide co-crystals

Abstract

Crystal engineering principles were employed in designing new co-crystals of hydrochlorothiazide (HCT). A variety of potential co-crystal formers were initially identified in a search of the Cambridge Structural Database with complementary hydrogen-bonding functionalities. Subsequent co-crystallization screening monitored by powder X-ray diffraction led to the discovery of new crystalline phases of HCT with pyrazinamide (1), 4,4′-bipyridine (2), 1,2-bis(4-pyridyl)ethane (3), and trans-1,2-bis(4-pyridyl)ethylene (4). All of the resulting co-crystals were thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the co-crystal 1 involves the formation of drug–drug co-crystals of HCT and pyrazinamide, which makes it a potential candidate for development of HCT formulations for combinational therapy.