Application of Box-Behnken Design in the Development of Nanostructured Lipid Carriers for an Anticancer Drug

Abstract

The present study aimed to develop and optimize Ceritinib-loaded Nanostructured Lipid Carriers (C-NSLCs) to enhance the solubility, entrapment efficiency, and sustained drug release of the BCS Class IV anticancer drug, Ceritinib, using the Box-Behnken Design (BBD). Capmul concentration (A), Egg Lecithin concentration (B), and Sonication time (C) were selected as independent variables, while Particle Size (Y1), Entrapment Efficiency (Y2), and Drug Release (Y3) were response variables. 17 experimental formulations were prepared and evaluated, and the data was analyzed using a quadratic polynomial model with ANOVA validation. The optimized formulation was prepared using 10% Capmul, 3% Egg Lecithin, and 5 minutes of sonication time, which resulted in a particle size of 214.23 nm, entrapment efficiency of 94.25%, and drug release of 85% over 48 hours. FTIR and DSC studies confirmed the compatibility and stability of Ceritinib with excipients, while SEM images revealed spherical, uniform nanoparticles with smooth and porous surfaces. In vitro release studies showed biphasic drug release with an initial burst followed by sustained release, following Korsemeyer-Peppas release kinetics (R² = 0.995), suggesting a diffusion-controlled non-Fickian release mechanism. Stability studies over six months under refrigerated, long-term, and accelerated conditions demonstrated minimal changes in particle size, entrapment efficiency, and drug content, indicating good formulation stability. The study concluded that C-NSLCs are a promising delivery system for improving the bioavailability and therapeutic efficacy of Ceritinib.