Formulation of dacarbazine-loaded cubosomes-part I: influence of formulation variables

The purpose of this study was to investigate the combined influence of three-level, three-factor variables on the formulation of dacarbazine (a water-soluble drug) loaded cubosomes. Box-Behnken design was used to obtain a second-order polynomial equation with interaction terms to predict response values. In this study, the selected and coded variables X(1), X(2), and X(3) representing the amount of monoolein, polymer, and drug as the independent variables, respectively. Fifteen runs of experiments were conducted, and the particle size (Y(1)) and encapsulation efficiency (Y(2)) were evaluated as dependent variables. We performed multiple regression to establish a full-model second-order polynomial equation relating independent and dependent variables. A second-order polynomial regression model was constructed for Y(1) and confirmed by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically, and they predicted the levels of independent coded variables X(1), X(2), and X(3) (-1, 0.53485, and -1, respectively) and minimized Y(1) while maximizing Y(2). These corresponded to a cubosome formulation made from 100 mg of monoolein, 107 mg of polymer, and 2 mg with average diameter of 104.7 nm and an encapsulation efficiency of 6.9%. The Box-Behnken design proved to be a useful tool to optimize the particle size of these drug-loaded cubosomes. For encapsulation efficiency (Y(2)), further studies are needed to identify appropriate regression model.