Development of sulfamethoxazole-succinimide cocrystal by mechanochemical cocrystallization – An insight into spectroscopic, electronic, chemical conformation and physicochemical properties

Abstract

Sulfamethoxazole is a sulphonamide bacteriostatic antibiotic having poor solubility, resulting in a high prescribed dose of 800 mg/day. Accordingly, these high doses relate to an increased risk of adverse effects. In this contribution, a novel cocrystal of sulfamethoxazole-succinimide was prepared by mechanochemical synthesis to modulate the physicochemical properties. X-ray diffraction, thermal, and spectroscopic analyses were used to characterize the cocrystal thoroughly. Also, to gain an insight into the optimized structural geometry, important functional frequencies, and electronic properties, the density functional theory was used. The contribution of auxiliary interactions and intermolecular interactions have been investigated by Hirshfeld surface analysis. Solubility and powder dissolution studies were performed to investigate the changes in the physicochemical properties. The cocrystal demonstrated an improvement in the solubility profile in aqueous media and an enhanced dissolution rate in the recommended dissolution media. Furthermore, accelerated stability studies under stress conditions were performed, where the cocrystal showed no indication of dissociation. The study demonstrates the significance of mechanochemical cocrystallization to modulate the physicochemical properties of an API, along with an insight into spectroscopic, electronic and chemical conformation.