Multivariate analysis of physicochemical characteristics of lipid based nanoemulsifying cilostazol--quality by design

Abstract

Simultaneous analysis of the effect of multiple formulation ingredients on the critical physico-chemical properties of lipid based nanoemulsifying cilostazol was studied using integrated quality by design approach. Cilostazol is a poorly soluble drug belonging to class II of the biopharmaceutics classification system. To improve the solubility and in turn bioavailability of cilostazol, a lipid based nanoemulsifying cilostazol was developed. Self nanoemulsifying system comprising of Capmul MCM (oily solubilizer), Tween 80 (surfactant); and Transcutol HP (cosolvent) was developed. A 2(3) full factorial experimental design was employed to optimize simultaneously the effect of levels of these three components on physico-chemical responses (viz. globule size, span, zeta potential, solubility, and dissolution efficiency at 30 min) of nanoemulsifying cilostazol. Graphical analysis using Pareto charts and Bayesian analysis along with mathematical modelling of the results allowed the identification and quantification of the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. The optimum formulation was a mixture of Capmul MCM, Tween 80 and Transcutol HP; 3:5:5 parts by weight. Optimized composition on dilution with water showed globule size; 215.2 nm with a span of 0.42. The nanoemulsifying formulation showed equilibrium solubility and dissolution efficiency; 9.82 mg/ml and 83.3% respectively, indicating significant improvement in comparison to pristine cilostazol. Interaction between oil and the cosolvent significantly affected the globule size and the span of the resultant nanoemulsion. Zeta potential was independent of selected formulation variables. The optimized formulation was adsorbed onto Neusilin US2 without affecting nanoemusifying ability of lipid based cilostazol composition.

Keywords: Adsorption; Cilostazol; Multivariate analysis; Nanoemulsion; Quality by design; Solubility.