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 (Y1), %transmittance (Y2), self-emulsification time (Y3), dissolution after 5 min and 40 min (Y4, Y5). Optimized formulation was characterized for various physicochemical properties. 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. 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.

中文翻译：

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Box-Behnken设计和期望功能在开发用于增强依折麦布溶出度的自纳米乳化药物递送系统的开发和优化中的应用

这项研究的重点是通过Box–Behnken设计（BBD）和可取性功能来提高溶出度，从而开发和优化BCS II类药物（依折麦布）的自纳米乳化药物递送系统（SNEDDS）。通过取油（Peceol），表面活性剂（Tween80）和助表面活性剂（Transcutol-P）生成伪三元相图，并确定了产生BBD的浓度范围。依泽替米贝-SNEDDS的组成是通过各种响应变量来优化的。球大小（Y1），透光率（Y2），自乳化时间（Y3），5分钟和40分钟后的溶解（Y4，Y5）。针对各种理化特性对优化配方进行了表征。选择具有最大纳米乳化面积的伪三元相图来配制SNEDDS。运用衍生的多项式方程和模型图来研究配方变量对响应的影响。观察到制剂组合物对应答的显着影响（p ＜0.05）。含油量最少（10％）和高表面活性剂（60％）的制剂显示出小球尺寸（24.4±2.07 nm），低乳化时间（55 s），高透光率（101.2％）和药物释放（5后49.21％）分钟； 40分钟后为95.27％）。基于期望函数，选择并重新制定了优化配方。发现优化配方（FF1）均匀，稳定，并显示出相似的观察到的和预测的响应。