Formulation of dacarbazine-loaded Cubosomes--part II: influence of process parameters.

The purpose of this study is to investigate the combined influence of process parameters (independent variables) such as homogenization speed (X(1)), duration (X(2)), and temperature (X(3)) during the preparation of dacarbazine-loaded cubosomes. Box-Behnken design was used to rationalize the influence of these three factors on two responses, namely particle size (Y(1)) and encapsulation efficiency (Y(2)). Independent and dependent variables were analyzed with multiple regressions to establish a full-model second-order polynomial equation. F value was calculated to confirm the omission of insignificant parameters or interactions of parameters from the analysis to derive a reduced-model polynomial equation to predict the Y(1) and Y(2) of dacarbazine-loaded cubosomes. Pareto charts were also obtained to show the effects of X(1), X(2), and X(3) on Y(1) and Y(2). For Y(1), there was a model validated for more accurate prediction of response parameter by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically and they predicted the levels of independent parameters X(1), X(2), and X(3) (0.889794, 0.11886, and 0.56201, respectively) and minimized Y(1). The optimal process parameters (homogenization's speed = approximately 24,000 rpm, duration = 5.5 min, and temperature = 76 degrees C) led to the production of cubosomes with 85.6 nm in size and 16.7% in encapsulation efficiency. The Box-Behnken design proved to be a useful tool in the preparation and optimization of dacarbazine-loaded cubosomes. For encapsulation efficiency (Y(2)), further studies are needed to enhance the result and improve the model for such water-soluble drug encapsulation in cubosomes.