Carvedilol solubility enhancement by multicomponent crystallization with coformers of benzoic acid, isonicotinamide, and saccharin

Abstract

Multicomponent crystallization is a method that can modify the physicochemical properties of Carvedilol (CVD), thereby increasing its solubility. Based on in silico screening the coformers (Benzoic Acid, Isonicotinamide, and Saccharin) showed non-covalent interactions with CVD, so the multicomponent crystal preparation of CVD by solvent evaporation method used these coformers with mole ratios of 1:1, 1:2, and 2:1. Multicomponent CVD:Isonicotinamide (1:2) exhibits increased saturation solubility of up to 140 mg/L and increased dissolution of up to 99.48%. The infra-red (IR) spectrum showed a peak shift, a thermogram pattern that was different from the DSC results, and a new peak on the XRD multicomponent crystal diffractogram indicating the formation of a new solid phase compared to pure Carvedilol. Therefore, the formation of multicomponent crystals can increase the solubility and dissolution rate of CVD, and all characteristics indicate the presence of interaction between CVD and Isonicotinamide, and the formation of a new solid phase.