Formulation of Dacarbazine-loaded Cubosomes—Part II: Influence of Process Parameters

Abstract

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 = ~24,000 rpm, duration = 5.5 min, and temperature = 76°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.