Development of Nanosponge Formulations of Rosuvastatin for Oral Delivery Using a Central Composite Design

Abstract

Background: Rosuvastatin (ROS) is an anti-hyperlipidaemic drug which reduces cholesterol levels, having poor solubility and low bioavailability (<20%). The objective of the present study was to increase ROS bioavailability by formulating nanosponges.Materials and Methods: Important quality features were identified using the Quality by Design (QbD) method. Central Composite Design (CCD) was utilized to design formulations. Eudragit L-100 (EL-100) and Polyvinyl Alcohol (PVA) were used as polymers and surfactants, respectively. Nanosponges were produced using emulsion solvent evaporation (RF1-RF15). The final formulations were assessed based on parameters including drug-excipient interaction, particle size, surface morphology, Entrapment Efficiency (%EE), and in vitro drug release. The Design Expert-13 (DOE) produced the optimized Formulation (RF16), which was utilized in the in vivo drug release Results: All Formulations (RF1-RF15) showed particle size of 99±0.84 nm to 305±0.26 nm, %EE 17.8±0.42 to 84.69±0.45, and drug release was 94.33±0.45% to 99.77±0.56% in 4 hr. Optimized Formulation (RF16) showed a particle size of 295±0.35 nm, % EE of 78.54±0.26 %, and drug release study of 95.13±0.63% in 3.5 hr. The in vivo studies showed Cmax, Tmax, AUC0-t, AUC0-α, MRT0-α of the pure drug and RF16 of 7.123μg/mL and 14.787 μg/mL, 1.5 and 2.5 hr, 19.56 μg/mL*hr and 25.71 μg/ mL*hr, 23.91 μg/ml*h, and 48.85 μg/mL*hr, 5.04 hr and 3.91 hr, respectively.Conclusion: The pharmacokinetic parameters RF16 demonstrate a 2-fold enhancement in the bioavailability of ROS nanosponges compared to the pure drug.

Keywords: Rosuvastatin; In vivo drug release; Central Composite Design; Eudragit L-100; Quality by Design