IMPLICATION OF CENTRAL COMPOSITE DESIGN IN THE DEVELOPMENT OF SIMVASTATIN-LOADED NANOSPONGES

Abstract

Objective: The present study’s objective was to apply a central composite design to develop the simvastatin-loaded nanosponge formulation to improve its oral bioavailability. Methods: With the help of a design expert (State-Ease version 13.0.1), a central composite design was selected for the formulation of simvastatin-loaded nanosponges by using a defined concentration of Eudragit L-100 (X1) and PVA (X2) as independent variables and particle size (Y1), percent (%) entrapment efficiency (EE) (Y2), in vitro drug release (Y3) as dependent variables. Fourteen (SF1-SF14) formulations were prepared using the emulsion solvent evaporation and evaluated for surface morphology, particle size, drug-excipient compatibility, %EE, and % drug release. The optimized model (SF14) obtained from a design expert was evaluated for in vivo pharmacokinetics in animal models. Results: SF14 was formulated and evaluated for morphology (shape and size) of the particle, % EE, in vitro % drug release, and its kinetics. The formulation showed particle size of 163±0.45 nm, 80.54 %±0.57 of EE, and 97.13%±0.38 of drug release at 8h. The release kinetics followed the zero-order and Higuchi mechanisms with non-fiction diffusion. In vivo results showed Cmax, Tmax, AUC0-t, AUC0-α, and MRT0-α for nanosponges were 0.175 µg/ml, 6 h, 1.561 µg/mlh, 1.755 µg/mlh, 11.77 h, respectively. Conclusion: The results indicated a significant increase in the bioavailability of the drug in nanosponges compared with standard drugs. The experimentally designed nanosponge formulations have been successfully developed, and evaluated parameters show that the nanosponge formulation of Simvastatin is a promising delivery through the oral route.