Formulation and Optimization of Nanosuspensions for Enhancing Simvastatin Dissolution Using Central Composite Design

Abstract

Simvastatin is a poorly water-soluble drug, and bioavailability from its crystalline form is very low. The purpose of this investigation was to increase the solubility and dissolution rate of simvastatin by the preparation of nanosuspensions with Pluronic F127 and zirconium oxide (ZrO2) beads using a wet-milling technique at the laboratory scale. Prepared nanosuspensions were evaluated for particle size and in vitro dissolution. A 3 2 central composite design was employed to study the effect of the independent variables (i.e., amount of Pluronic F127, X1, and amount of ZrO2, X2) on the dependent variables (i.e., particle size [nm] and percentage of drug released after 10 min, Q10). The relationship between the dependent and independent variables was further elucidated using multiple liner regression analysis (MLRA) and contour plots. The results show that nanosuspensions prepared with the higher concentrations of Pluronic F127 and the higher quantities of ZrO2 (up to 8 g) reduced the particle size and enhanced the dissolution rate of the formulation. The dissolution rate of the optimized nanosuspension was enhanced (64% in 10 min) relative to that of a micronized suspension of simvastatin (3.5% in 10 min), mainly because of the formation of nanosized particles. These results show that the preparation of simvastatin-loaded nanosuspensions significantly improved the in vitro dissolution rate, thus possibly enhancing the fast onset of therapeutic drug effect.