星点设计效应面法优化氟比洛芬纳米结构脂质载体的处方

Application of central composite design-response surface methodology to the formulation of flurbiprofen-loaded nanostructured lipid carriers

目的采用星点设计法以总评"归一值"为指标优化氟比洛芬纳米结构脂质载体的处方。方法以粒径、包封率、载药量、Zeta电位等为评价指标,考察了氟比洛芬(flurbiprofen,FP)加入量、卵磷脂用量、吐温-80和泊洛沙姆188的总量以及去氧胆酸钠的用量对FP-NLC性质的影响。用多元线性方程和二次多项式描述各指标及总评"归一值"和3个影响因素之间的数学关系,根据总评"归一值"的最佳数学模型描绘效应面,选择最佳处方,并进行预测分析。结果 4个影响因素和4个评价指标及总评"归一值"之间存在定量关系。优选的最佳处方为氟比洛芬0.222 g,卵磷脂0.300 g,吐温-80和泊洛沙姆188总质量2.000 g,去氧胆酸钠0.100 g。优化处方各指标的预测值和目标值接近。结论所建立的模型预测性良好,可用于预测和优化氟比洛芬纳米结构脂质载体处方。

Objective To obtain a optimized formulation of flurbiprofen-loaded nanostructured lipid carriers by using central composite design-response surface methodology. Methods The effect of formulation variables （ amount of flurbiprofen, amount of lecithin, amount of Poloxamer 188 and Tween-80, amount of sodium deoxycholate ） on a number of response variables were systemically investigated. The response variables were particle size, zeta potential, entrapment efficiency and drug loaded. A desirability function that combines these four response variables was constructed. A second-order polynomial equation was fitted to the data, and the resulting equation was used to predict the responses in the optimal region. Results All the investigated response variables were found to be highly dependent on the formulation variables. It was found that optimum overall desirability of the flurbiprofen-loaded nanostructured lipid carriers can be obtained at 0. 222 g of flurbiprofen,0. 300 g of Lecithin,2. 000 g of poloxamer 188 and Tween-80, and at 0. 100 g of sodium deoxycholate. The experimental values of the response Variables highly agree with the predict values. Conclusions Central composite design-response surface methodology is successfully used to optimize the preparation of flurbiprofen-loaded nanostructured lipid carders. Overall desirability can be used to represent the most desirable variables in experimental design.