Formulation and optimization of itraconazole proniosomes using box behnken design

Abstract

Objective: The aim of the present study was to obtain an optimized formula of itraconazole (ITC) proniosomes using Box Behnken design. Methods: Itraconazole proniosomes were prepared using span 60 and/or brij 35 as surfactants, cholesterol and lecithin as a penetration enhancer by slurry method. Various trials have been carried out for investigation of proniosomes. Parameters such as entrapment efficiency (EE%), in vitro drug release, zeta potential, vesicle size and Transmission Electron Microscope were assessed for evaluation of proniosomes. Results: Entrapment efficiency (EE%) was found to be between 78.56% and 95.46%. The release profile of itraconazole proniosomes occurred in two distinct phases, an initial phase for about 8 h, followed by a slow phase for 16 h. The release pattern shown by these formulations was Higuchi diffusion controlled mechanism. The zeta potential values for all itraconazole proniosomes were in the range of-21.71 to-34.53 mV which confirms their stability. All itraconazoleproniosomes formula was found to be nano-sized and were appeared to be spherical in shape with sharp boundaries. One way analysis of variance (ANOVA) study showed that HLB (X1) had the main effects on most responses (Y). Conclusion: Box behnken design facilitates optimization of the formulation ingredients on entrapment efficiency, in vitro release of itraconazole proniosomes, zeta potential and vesicle size. Finally, an optimum level of factors was provided by the optimization process.