Ranolazine Co-Crystal: Molecular Docking, Coformer Selection, In vitro, In vivo Pharmacokinetic Assesment in Rat...

Ranolazine is an antianginal agent, but its low water solubility and bioavailability limit its therapeutic use. In this study, we have attempted to improve the solubility and bioavailability of Ranolazine by forming co-crystals with selected co-formers. In silico screening was first performed to select the potential co-formers forming stable co-crystals with Ranolazine. Based on the predicted interactions and physicochemical properties, co-formers 2-amino caffeine, nicotinamide, and benzamide were selected. Co-crystals were synthesized by solvent drop grinding, antisolvent addition and slow evaporation methods. Characterization of synthesized co-crystals was carried out by UV, FTIR, and DSC techniques to confirm the successful formation and structural properties. In vitro dissolution studies showed that the co-crystals significantly improved the release rate of Ranolazine as compared to the pure drug. A pharmacokinetic study used a validated RP-HPLC method to quantify Ranolazine and its co-crystals in rat plasma after oral administration. The analysis showed enhanced plasma concentrations (Cmax) for Ranolazine co-crystals, which indicated improved bioavailability. The RP-HPLC method was found to be accurate, sensitive, linear and specific following ICH guidelines, with hydrochlorothiazide as the internal standard. This study demonstrated the potential of in silico screening for selecting appropriate co-formers to enhance the physicochemical properties of Ranolazine, and the co-crystals have shown potential for improved therapeutic outcomes. These results indicate that further preclinical and clinical investigations of Ranolazine co-crystals could effectively improve drug performance.