木犀草素纳米混悬剂的制备与质量评价

Preparation and quality evaluation of luteolin nanosuspension

关键词:  木犀草素  纳米混悬剂  介质碾磨法  单因素实验设计  Box-Behnken实验设计  体外溶出

Key words:  luteolin  nanosuspension  wet media milling method  single factor experiment design  Box-Behnken experimental design  in vitro dissolution

摘要:

[目的] 采用介质碾磨法制备木犀草素纳米混悬剂，并评价其质量。[方法] 借助单因素实验设计考察法优化了制备工艺参数并确定了处方中稳定剂和表面活性剂的种类，并以木犀草素纳米混悬剂的粒径分布（Y₁）和Zeta电位（Y₂）作为评价指标，以处方中的药物浓度（X₁），稳定剂浓度（X₂）和表面活性剂浓度（X₃）作为考察因素，通过Box-Behnken实验设计优化其处方；采用扫描电镜观察木犀草素纳米混悬剂的微观形态；并比较了木犀草素原料药与纳米混悬剂的体外溶出状况。[结果] 通过单因素实验考察确定木犀草素纳米混悬剂的制备工艺参数为：碾磨介质与混悬剂体积之比为1：1，研磨速度为2 500 r/min，研磨时间为4 h，稳定剂为羟丙基纤维素（HPC SL），表面活性剂为维生素E聚乙二醇1000琥珀酸酯（TPGs），经Box-Behnken实验设计优化得到木犀草素纳米混悬剂的最优处方为：药物浓度为28.0 mg/mL，稳定剂浓度为1.5 mg/mL，表面活性剂浓度为0.2 mg/mL；按照该处方制备的木犀草素纳米混悬剂平均粒径为（324.3±21.6）nm，Zeta电位为（-31.4±0.9）mV，在扫描电镜下可以观察到呈颗粒状均匀分布；木犀草素纳米混悬剂的药物溶出速率显著高于原料药。[结论] 本研究将木犀草素制备成纳米混悬剂，可显著提高其体外药物溶出速率，有望改善口服生物利用度高，提高药物治疗效果。

Abstract:

[Objective] To prepare luteolin nanosuspension by wet media milling method and evaluate its quality.[Methods] The single-factor experimental design method was used to optimize the process parameters and determine the types of stabilizers and surfactants in the formulation. The particle size distribution and Zeta potential of luteolin nanosuspension were used as evaluation indicators,the luteolin concentration,the stabilizer concentration and the surfactant concentration were taken as the investigation factors,the formulation of luteolin nanosuspension was optimized by Box-Behnken experiment design method. The microscopic morphology of the luteolin nanosuspension was observed by scanning electron microscopy. The in vitro dissolution of luteolin raw materials and nanosuspension was compared.[Results] The process parameters and formulation of luteolin nanosuspension were determined by single factor experiment:milling media volume was 1:1,milling speed was 2 500 r/min,the milling time was 4 h,the stabilizer was HPC SL,and the surfactant was TPGs. The optimal formulation of luteolin nanosuspension was optimized by Box-Behnken experimental design:drug concentration was 28.0 mg/mL,stabilizer concentration was 1.5 mg/mL,surfactant concentration was 0.2 mg/mL;The average particle size and Zeta potential of the luteolin nanosuspension prepared according to the optimized formulation were (324.3±21.6) nm and (-31.4±0.9) mV respectively,and a uniform particle distribution could be observed under scanning electron microscopy. The drug dissolution rate of luteolin nanosuspension was significantly higher than that of the luteolin.[Conclusion] In this study,luteolin nanosuspension could significantly improve the drug dissolution rate in vitro,and it was expected to improve oral bioavailability and improve drug treatment.