Gurumukhi Vishal C, Sonawane Vivek P, Tapadiya Ganesh G, Bari Sanjaykumar B, Surana Sanjay J, Chalikwar Shailesh S
Department of Pharmaceutical Quality Assurance, Shreeyash Institute of Pharmaceutical Education and Research, Aurangabad 431010, Maharashtra, India.
Department of IPQA, Micro Labs Ltd, Verna Industrial Estate, Goa 403722, India.
Heliyon. 2023 Apr 18;9(4):e15404. doi: 10.1016/j.heliyon.2023.e15404. eCollection 2023 Apr.
The present work deals with QbD-based development of FEB-loaded nanoemulsion (FEB-NE) in order to enhance bioavailability and permeability. In the beginning, the risk assessment was performed on different experimental variables using the Ishikawa diagram followed by FMEA study in order to find critical process parameter (CPP) and critical material attributes (CMAs). To build quality in nanoemulsion, the quality target product profiles (QTPP) and critical quality attributes (CQAs) were determined. The different batches of FEB-NE were produced by the microemulsification-probe sonication method. Effect of varying levels of independent variables such as oil concentration (X), S concentration (X), and amplitude (X) on responses such as globule size (Y), zeta potential (Y), and entrapment efficiency (Y) were studied using Box-Behnken design (BDD). FEB-NE formulation was optimized using a graphical and numerical method. The optimized formulation concentrations and their responses (CQAs) were located as design space in an overlay plot. The spherical shapes of globules were visualized by surface morphology using AFM and TEM. dissolution study showed 93.32% drug release from the optimized FEB-NE formulation. The drug release mechanism followed by the formulation was the Higuchi-matrix kinetics with a regression coefficient of 0.9236 (R). FEB-NE showed enhanced permeability using PAMPA (artificial non-cell membrane) and everted gut sac model method. The developed optimized FEB-NE exhibited the enhancement of bioavailability by 2.48 fold as compared to FEB-suspension using Wistar rats suggesting improvement of solubility of a lipophilic drug. The optimized batch remained stable for 90 days at 4 °C and 25 °C. Thus, QbD-based development of FEB-NE can be useful for a better perspective on a commercial scale.
本研究致力于基于质量源于设计（QbD）理念开发载有非诺贝特（FEB）的纳米乳剂（FEB-NE），以提高其生物利用度和渗透性。首先，使用石川图对不同实验变量进行风险评估，随后进行失效模式与效应分析（FMEA）研究，以确定关键工艺参数（CPP）和关键物料属性（CMA）。为确保纳米乳剂的质量，确定了质量目标产品概况（QTPP）和关键质量属性（CQA）。采用微乳化-探头超声法制备了不同批次的FEB-NE。使用Box-Behnken设计（BBD）研究了油浓度（X1）、表面活性剂浓度（X2）和振幅（X3）等自变量的不同水平对球粒大小（Y1）、zeta电位（Y2）和包封率（Y3）等响应的影响。采用图形和数值方法对FEB-NE配方进行了优化。在叠加图中，将优化后的配方浓度及其响应（CQA）定位为设计空间。使用原子力显微镜（AFM）和透射电子显微镜（TEM）通过表面形态观察球粒的球形形状。溶出度研究表明，优化后的FEB-NE配方的药物释放率为93.32%。该配方遵循的药物释放机制为Higuchi基质动力学，回归系数为0.9236（R）。使用平行人工膜渗透模型（PAMPA，人工无细胞膜）和外翻肠囊模型方法，FEB-NE显示出增强的渗透性。与使用Wistar大鼠的FEB混悬液相比，所开发的优化FEB-NE的生物利用度提高了2.48倍，表明亲脂性药物的溶解度得到了改善。优化批次在4℃和25℃下可稳定保存90天。因此，基于QbD的FEB-NE开发对于商业规模的更好前景可能是有用的。
