Structural and physicochemical aspects of hydrochlorothiazide co-crystals
CrystEngComm, 2014, 16,6996-7003
DOI: 10.1039/C4CE00666F, Paper
DOI: 10.1039/C4CE00666F, Paper
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Corresponding authors
aPharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
E-mail: xuefengmei@simm.ac.cn
The drug-drug co-crystal of hydrochlorothiazide with pyrazinamide is a potential candidate for development of hydrochlorothiazide formulations for combinational therapy.
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.
