Application of Box-Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe

Background This study is focused on developing and optimizing a self-nanoemulsifying drug delivery system (SNEDDS) of BCS class II drug (ezetimibe) through Box-Behnken design (BBD) and desirability function for enhanced dissolution. Pseudoternary phase diagrams were created by taking oil (Peceol), surfactant (Tween80), and co-surfactant (Transcutol-P) and the concentration ranges were identified for generating BBD. The composition of ezetimibe-SNEDDS was optimized through various response variables viz. globule size (Y-1), %transmittance (Y-2), self-emulsification time (Y-3), dissolution after 5 min and 40 min (Y-4, Y-5). Optimized formulation was characterized for various physicochemical properties. Results Pseudoternary phase diagram having maximum nano-emulsification area was selected to formulate SNEDDS. Derived polynomial equation and model graphs were exercised to investigate the impact of formulation variables on the responses. Significant effect of formulation composition on the responses was observed (p < 0.05). The formulation with least oil (10%) and high surfactant (60%) exhibited low globule size (24.4 +/- 2.07 nm), low emulsification time (55 s) but high %transmittance (101.2%) and drug release (49.21% after 5 min; 95.27% after 40 min). Based on the desirability function, the optimized formulation was selected and reformulated. The optimized formulation (FF1) was found to be uniform, stable, and showed similar observed and predicted responses. Conclusion The potential of SNEDDS in improving the dissolution profile of weakly soluble drug and the applicability of BBD with desirability function in optimizing a SNEDD formulation has made it possible to identify the impact of various independent variables on optimization of the formulation for better responses.