Tuning solubility and stability of hydrochlorothiazide co-crystals

Sanphui, Palash and Rajput, Lalit (2014) Tuning solubility and stability of hydrochlorothiazide co-crystals. In: ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 70 (1, SI). pp. 81-90.

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Abstract

Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotinamide, succinamide, p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N-H center dot center dot center dot O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal with p-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5-2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.

Item Type:	Journal Article
Publication:	ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE
Publisher:	WILEY-BLACKWELL
Additional Information:	Copyright for this article belongs to the WILEY-BLACKWELL, NJ USA
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	06 Mar 2014 06:56
Last Modified:	06 Mar 2014 06:57
URI:	http://eprints.iisc.ac.in/id/eprint/48494

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