DESIGN, 23 FACTORIAL OPTIMIZATION AND IN VITRO–IN VIVO PHARMACOKINETIC EVALUATION OF ROSUVASTATIN CALCIUM LOADED POLYMERIC NANOPARTICLES

Abstract

Objective: The objective is to incorporate low bioavailable Rosuvastatin Calcium (20%) into polymeric nanoparticles (PNs) to improve its biopharmaceutical properties of Rosuvastatin Calcium. Methods: The PNs were prepared by solvent evaporation method by applying 23 factorial designs. The formulated PN are investigated for particle size (PS) and shape, zeta potential (ZP), polydispersity index (PI) and entrapment efficiency (EE), in vivo pharmacokinetic. Results: Among 8 formulations, PN7 shows least PS of 159.9±16.1 nm, which enhance the dissolution, surface area and permeability; ZP of-33.5±1.54 mV, which shows good stability; PI of 0.587±0.16 shows monodisperse distribution pattern; high EE of about 94.20±2.46 %; percentage yield of 96.80±2.08 %; maximum in vitro drug release of about 96.54±2.02 % at 24 h with controlled and predetermined release pattern. PN7 drug release obeys zero-order release kinetics, non-fickian diffusion mechanism with r2 value>0.96 and release exponent ‘n’ value falls between 0.5-0.8 for peppas kinetic model i.e., the mechanism of drug diffusion is based on polymer relaxation. In vivo pharmacokinetic studies illustrate enhance in AUCo-α in mg/ml, which proves a significant enhancement of bioavailability of Rosuvastatin Calcium by PNs. Conclusion: This PN shows a significant enhancement of bioavailability by minimizing the dose-dependent adverse side effects of rosuvastatin calcium.