A Novel Co-crystallization Technique to enhance the Physicochemical property of BCS Class-II drugs using Efavirenz as a model drug

Abstract

Pharmaceutical co-crystallization, a novel technique, provides for alteration and tailoring of physicochemical properties of active pharmaceutical ingredients (API) notwithstanding maintaining the intrinsic activity of the drug molecule. In the present work, co-crystals of efavirenz (EFA) were prepared with selected conformers of GRAS (Generally Recognized as Safe) status wise salicylic acid (SA) and benzoic acid (BA) using solution crystallization method to improve its dissolution. The assembly of crystal structure was evaluated by means of fourier transformation infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Saturation solubility and in vitro dissolution studies were further employed to investigate co-crystals. Equilibrium solubility profile of EFA-SA and EFA-BA exhibits an enhancement of 1.60 and 1.29 folds of solubility of efavirenz co-crystals as compared to the pure drug. Pharmacokinetic study performed in rats showed AUC0-∞ for co-crystals formulation was higher (13.15±0.02µg hmL−1) than the pure drug suspension formulation 7.85±0.03µg hmL−1. Statistically, AUC0-t of the co-crystal formulation was significantly higher (p<0.05) as compared to pure drug suspension formulation. Higher amount of drug concentration in blood indicated better systemic absorption of efavirenz from co-crystals formulation as compared to the pure drug suspension formulation.