Crystallographic Modification of Rosuvastatin Calcium: Formulation, Characterization and Pharmacokinetic Evaluation for Enhanced Dissolution, Stability and Bioavailability

Rosuvastatin calcium is a promising lipid-lowering agent and the drug of choice in hyperlipidemia. Conventional solid oral delivery of rosuvastatin is limited by its poor solubility and ultimately poor bioavailability. An attempt was made to fabricate the cocrystals of RSC for enhancing solubility and bioavailability. Cocrystals were prepared by a microwave synthesiser-assisted solvent evaporation technique with multiple cocrystal formers. Rosuvastatin-Ascorbic acid (RSC-AA) cocrystals showed the highest solubility (~5-fold increased) amongst all twenty drug-coformer combination (DCC). RSC-AA cocrystals (1:1 ratio) were further characterized by various analytical techniques like FTIR, DSC and XRD to confirm the formation of cocrystals. RSC-AA cocrystals also showed improved flow properties and compressibility in comparison with pure drug, and it was demonstrated using the SeDeM diagram. RSC-AA cocrystals were further formulated into an immediate-release tablet by implementing experimental optimization. Comparative dissolution study of the cocrystal and pure drug tablet revealed improved dissolution after cocrystallization. RSC-AA cocrystal tablet showed the % drug release of 95.61 ± 3.94 while RSC pure drug showed the drug release of 67.83 ± 3.29. In vivo pharmacokinetic analysis showed significant improvement in systemic availability and cumulative absorption of the drug. The peak plasma concentration (Cmax) for RSC pure drug was 13.924 ± 0.477 μg/mL, while RSC-AA cocrystals showed a peak plasma concentration of 22.464 ± 0.484 μg/mL. Area Under Curve (AUC) of RSC-AA cocrystal was also significantly greater compared to the pure drug. In the stability study analysis, the shelf life was calculated from a graphical method and was found to be around 34.58 months for RSC-AA cocrystal tablets and 19.87 months for RSC pure drug tablets, which indicates improved stability with cocrystallization. Overall, the cocrystallization resulted in significant improvement in dissolution and solubility of RSC.