Preparation and Physical Characterization of a Diclofenac-Ranitidine Co-precipitate for Improving the Dissolution of Diclofenac

Abstract

Mixing aqueous solutions of sodium diclofenac (DIC-Na) and ranitidine hydrochloride (RAN·HCl) afforded an off-white solid (DIC-RAN) that was investigated from the microscopic, thermal, diffractometric, spectroscopic, and functional (chemometrics-assisted dissolution) points of view. The solid has a 2:1 (DIC:RAN) molar ratio according to 1H nuclear magnetic resonance spectroscopy. It is thermally stable, displaying a broad endothermic signal centered at 105°C in the thermogram, and its characteristic reflections in the powder X-ray diffractogram remained unchanged after a 3-month aging period. Scanning electron microscopy micrographs uncovered its morphology, whereas the spectral data suggested an interaction between the carboxylic acid of DIC and the alkyldimethylamino moiety of RAN. The dissolution of DIC-RAN was monitored at different pH values by an ultraviolet/chemometrics procedure, being complete within 5 min at pH 6.8. This compares favorably with the dissolution of a DIC-Na sample of the same particle size.