Abstract Amiodarone hydrochloride (AMH) is a potent anti-arrhythmic drug used for the treatment of ventricular tachycardia and ventricular fibrillation, but its clinical utility is limited by low aqueous solubility (~ 0.2 mg/mL) and poor dissolution. Co-crystallisation offers a promising strategy to improve the solubility and bioavailability of Biopharmaceutics Classification System Class II drugs. This study focused on developing an immediate-release tablet containing AMH co-crystals with enhanced solubility and dissolution characteristics. Co-former selection was guided by excess enthalpy and Hansen solubility parameter calculations, leading to the synthesis of two co-crystals, amiodarone–tartaric acid and amiodarone–phthalic acid, via liquid-assisted grinding. Characterisation was performed using powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. The amiodarone–tartaric acid co-crystal exhibited superior solubility (0.891 mg/mL and 0.583 mg/mL in acetate buffer and water, respectively) compared with the pure drug. Polymer screening identified polyethylene glycol 4000 as optimal for controlling solution-mediated phase transformation. The tablet formulation, optimised using a Design of Experiments approach, achieved more than 90% drug release in 20 min compared with 95% in 120 min for a marketed product. Stability studies confirmed retention of crystallinity, solubility, and assay after six months, demonstrating the formulation’s robustness and potential clinical applicability. Graphical Abstract
Jha et al. (Tue,) studied this question.