Formulation Design and Optimization of Modified-Release Microspheres of Diclofenac Sodium

Abstract

The present study deals with the preparation of microspheres of diclofenac sodium using cross-linked poly(vinyl alcohol) (PVA). A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for developing the microspheres. The PVA to the drug ratio X₁ and amount of glutaraldehyde cross-linking agent X₂ were chosen as the independent variables. The time required for 50% drug dissolution t₅₀ in phosphate buffer (pH 7.2) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable t₅₀. Based on the results of multiple linear regression analysis and F statistics, it may be concluded that sustained action can be obtained when X₁ and X₂ are kept at high levels. The X₁X₂ interaction was found to be statistically significant. A response surface plot is presented to show the effects of X₁ and X₂on t₅₀. The drug release pattern fit the Higuchi model well. A model was validated for accurate prediction of the drug dissolution profile with constraints on the percentage drug release in the first, fifth, and seventh hours. The data of a selected batch were subjected to an optimization study, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.