Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy, Pune, India.
Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy, Pune, India.
Colloids Surf B Biointerfaces. 2014 Mar 1;115:29-36. doi: 10.1016/j.colsurfb.2013.11.019. Epub 2013 Nov 19.
Simultaneous analysis of the effect of multiple formulation ingredients on the critical physico-chemical properties of lipid based nanoemulsifying cilostazol was studied using integrated quality by design approach. Cilostazol is a poorly soluble drug belonging to class II of the biopharmaceutics classification system. To improve the solubility and in turn bioavailability of cilostazol, a lipid based nanoemulsifying cilostazol was developed. Self nanoemulsifying system comprising of Capmul MCM (oily solubilizer), Tween 80 (surfactant); and Transcutol HP (cosolvent) was developed. A 2(3) full factorial experimental design was employed to optimize simultaneously the effect of levels of these three components on physico-chemical responses (viz. globule size, span, zeta potential, solubility, and dissolution efficiency at 30 min) of nanoemulsifying cilostazol. Graphical analysis using Pareto charts and Bayesian analysis along with mathematical modelling of the results allowed the identification and quantification of the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. The optimum formulation was a mixture of Capmul MCM, Tween 80 and Transcutol HP; 3:5:5 parts by weight. Optimized composition on dilution with water showed globule size; 215.2 nm with a span of 0.42. The nanoemulsifying formulation showed equilibrium solubility and dissolution efficiency; 9.82 mg/ml and 83.3% respectively, indicating significant improvement in comparison to pristine cilostazol. Interaction between oil and the cosolvent significantly affected the globule size and the span of the resultant nanoemulsion. Zeta potential was independent of selected formulation variables. The optimized formulation was adsorbed onto Neusilin US2 without affecting nanoemusifying ability of lipid based cilostazol composition.
采用集成质量设计方法研究了多种制剂成分对基于脂质的西洛他唑纳米乳的关键物理化学性质的影响。西洛他唑是一种属于生物药剂分类系统 II 类的低溶解度药物。为了提高西洛他唑的溶解度，进而提高其生物利用度，开发了基于脂质的西洛他唑纳米乳。自纳米乳系统由 Capmul MCM（油性增溶剂）、Tween 80（表面活性剂）和 Transcutol HP（共溶剂）组成。采用 2(3)完全因子实验设计同时优化这三种成分的水平对纳米乳西洛他唑的物理化学响应（即粒径、跨度、Zeta 电位、溶解度和 30 分钟时的溶解效率）的影响。使用 Pareto 图和贝叶斯分析进行图形分析以及对结果进行数学建模，可确定并量化对所选响应有影响的制剂变量。将拟合数据的多项式方程用于预测具有最佳响应的组成。最佳配方是 Capmul MCM、Tween 80 和 Transcutol HP 的混合物；重量比为 3:5:5。用优化后的配方与水稀释后，粒径为 215.2nm，跨度为 0.42。纳米乳制剂的平衡溶解度和溶解效率分别为 9.82mg/ml 和 83.3%，与原始西洛他唑相比有显著提高。油相与共溶剂之间的相互作用显著影响所得纳米乳的粒径和跨度。Zeta 电位与所选制剂变量无关。优化后的配方被吸附在 Neusilin US2 上，而不影响基于脂质的西洛他唑制剂的纳米乳形成能力。
