Application of Central Composite Design for Formulation and Optimization of Solid Dispersion for Dissolution Rate Enhancement of BCS Class II Drug

Abstract

The objective of this research work was to develop solid dispersion of Fluvastatin sodium (FLS-SD) by solvent evaporation technique for dissolution enhancement of Fluvastatin sodium (FLS). Furthermore, central composite design (CCD) was applied for studying the effect of drug: polymer (w/w) (X1) and surfactant concentration (% w/v) (X2) on dependent variables T50% (Minutes) (Y1), Q90(%) (Y2) and percentage drug content (Y3). Thirteen experimental runs were performed as per CCD design layout and analyzed. The model was exceptional fitted in quadratic model as indicated by lack of fit of p-value more than 0.05. An optimized FLS-SD composition having 0.998 desirability function was explored using Design-Expert software. The theoretical values of t50%, Q90 and % drug content for optimized FLS-SD given by software were 23 min, 94.289% and 88.515%, respectively. The percentage cumulative drug release from FLS, physical mixture and FLS-SD was found 25.43%, 27.54%, and 93.6% within 2 hour which demonstrated superior and significant dissolution enhancement of FLS (*p < 0.05). The r2 for the Zero-order, First-order, Korsmeyer-peppas (K-P), and Higuchi models for FLS-SD were 0.8336, 0.7594, 0.9539 and 0.9234, respectively. K-P model was found superior (y = 0.426x +1.1259, r2 = 0.9539) and ‘n’ value was 0.426(n <0.45) which revealed fickian drug release from FLS-SD. This research work concluded that solid dispersion formulation by solvent evaporation technique could be successfully utilized for dissolution enhancement of BCS class II drug.