Hot melt extrusion-driven cocrystallization of aceclofenac with nicotinamide: A strategy to enhance solubility, bioavailability, and therapeutic effect.

Aceclofenac (ACF) is a commonly used non-steroidal anti-inflammatory drugs (NSAID) for numerous inflammatory conditions; however, its therapeutic potential is limited due to suboptimal solubility. Pharmaceutical cocrystals have demonstrated favorable and sustainable results in improving the physicochemical and biopharmaceutical characteristics of poorly soluble drugs. To enhance the solubility, dissolution rate, and bioavailability of ACF, we aimed to prepare cocrystals of this biopharmaceutics classification system (BCS) class II drug with a coformer including nicotinamide (NCT), using hot melt extrusion (HME) and liquid-assisted grinding (LAG) methods. ACF-NCT cocrystals synthesized using these methods were characterized using various methods and were further assessed for in vitro anti-osteoporotic and in vivo anti-arthritic activities. The results indicate that both LAG and HME cocrystals demonstrated significant improvement in solubility and dissolution profile compared to pure ACF. However, among these two methods, HME offered more advantages, including better solubility and dissolution profile, than the LAG method. The cocrystals achieved a remarkable 6.15-fold increase in solubility and ⁓3-fold enhancement in dissolution over pure ACF. The relative bioavailability of ACF-NCT HME cocrystal was 249.98% of pure ACF, indicating an improvement in oral bioavailability. The in vivo anti-arthritic activity also demonstrated significant improvement when compared to pure ACF. ACF-nicotinamide cocrystals prepared by hot melt extrusion achieved remarkable gains in solubility, bioavailability, and therapeutic efficacy, providing a promising strategy to overcome ACF's clinical limitations.