Formulation and In Vivo Evaluation of Trilayer Matrix Tablets of Rosuvastatin Solid Dispersions by Geomatrix Technology

Abstract

The current research aims to enhance the aqueous solubility and sustains the drug release of rosuvastatin BCS Class II drug. Fifteen (15) solid dispersion (SD) formulations of rosuvastatin were prepared by solvent evaporation technique and evaluated. In vitro drug dissolution study indicated a higher drug dissolution rate for SD13 of 99.74 ± 5.39 % within 60 min. Eight formulations of rosuvastatin trilayer matrix tablets (AF10- HF10) were prepared using optimized SD13 by direct compression method. These trilayer formulations are characterized for flow properties and physicochemical parameters. The maximum drug release was exhibited by trilayer matrix formulation (HF10) of 99.48 ± 5.40 % throughout 24 hours. The zero-order described the optimized formulation (HF10) release profile and best fitted to Higuchi and Korsmeyer-Peppa’s model. The results demonstrated the sustainability of rosuvastatin trilayer tablets with enhanced release time and linearity up to 24 hours. From in vivo bioavailability studies, Cmax of the rosuvastatin optimized ER tablets and the marketed product was found to be 28.46 ± 0.07 ng/mL and 30.94 ± 0.75 ng/mL, respectively. Tmax of both rosuvastatin optimized ER tablets formulation and rosuvastatin marketed product was 5 ± 0.06 and 4 ± 0.03 h, respectively. AUC0-∞ infinity for the optimized formulation was higher (395.54 ± 1.37 ng.h/mL) than the rosuvastatin marketed product formulation 212.54 ± 0.42 ng.h/mL. Statistically, the AUC0-t of the optimized ER tablets formulation was significantly higher (p is less than  0.05) than rosuvastatin marketed product formulation. In vivo, pharmacokinetic studies in rabbits confirmed the prolonged-release by showing an increase in bioavailability for rosuvastatin from optimized ER tablets than marketed formulation.