Box-Behnken响应面法优化基于茶皂素的香叶木苷纳米混悬剂及体外评价  

Optimization of diosmin nanosuspension stabilized by tea saponin through Box-Behnken design and in vitro evaluation

作　　者：曹怡 李小芳[1] 王娴 梁由单 代小琳 卢静 CAO Yi;LI Xiao-fang;WANG Xian;LIANG You-dan;DAI Xiao-lin;LU Jing(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]成都中医药大学药学院,四川成都611137

出　　处：《中药与临床》2024年第1期28-34,共7页Pharmacy and Clinics of Chinese Materia Medica

基　　金：四川省科技厅:基于“药效组分-粒子复合”模式纳米复合粒子的制备及其稳态增效机制的研究(编号:2019YFS0113);四川中医药大健康产业发展与乡村振兴研究中心项目:乡村振兴背景下中药智能管理实践路径研究(编号:DJKYB202215)。

摘　　要：目的:以植物皂苷茶皂素作为稳定剂制备香叶木苷纳米混悬剂(diosmin nanosuspension,DSN-NS),优化其处方工艺并进行体外评价。方法:以平均粒径和多分散指数(PDI)为评价指标,以DSN浓度,茶皂素浓度,剪切时间和均质压力四个影响显著的因素进行Box-Behnken响应面实验设计优化,优选出DSN-NS最佳的处方工艺。最佳工艺制备的DSN-NS冻干后得香叶木苷纳米晶(diosmin solid nanoparticals,DSN-SN),进行理化性质表征和体外溶出度测定。结果:最佳处方工艺为:0.090%(w/v)茶皂素,4.50 mg·mL^(-1)香叶木苷,剪切速度13000 rpm,剪切时间为4.0 min,均质压力为76 MPa,均质次数8次。制得的DSN-NS平均粒径为(474.9±6.7)nm,PDI为0.292±0.009,建立的DSN-NS制备工艺稳定,方法可靠。加入5.0%的甘露醇作为冻干保护剂制得DSN-SN,扫描电镜显示纳米晶成品呈不规则长条状结晶,透射电镜结果显示香叶木苷纳米粒大小较均匀。溶出度结果显示DSN-SN的体外溶出度明显高于原料药。结论:以植物皂苷茶皂素为稳定剂制备的DSN-NS,不仅制备方法简单,而且能显著改善DSN的溶解性和生物利用度,为DSN制剂的多元开发提供参考。Objective:Diosmin nanosuspension(DSN-NS)was prepared with tea saponin as stabilizer,and its formulation was optimized and evaluated in vitro.Method:Box-Behnken design was carried out in investigating DSN concentration,stabilizer concentration,shear time and homogeneous pressure to optimize the formulation and process of DSN-NS with the average particle size and the polydispersion index(PDI)as evaluation indexes.DSN-NS was transformed into Diosmin solid nanoparticals(DSN-SN)by freeze-drying,and their physicochemical properties were characterized and in vitro dissolution rate was detected by UV-Vis.Result:The optimal formulation process was as follows:0.090%tea saponin,4.50 mg·mL^(-1)DSN,shear rate of 13000 rpm,shear time of 4.0 min,homogenizing pressure of 76 MPa,homogenizing times of 8.The average particle size of the prepared DSN-NS was(474.9±6.7)nm,and the PDI was 0.292±0.009.The established DSN-NS preparation process was stable and reliable.DSN-SN was prepared by adding 5.0%mannitol as lyoprotectant.Scanning electron microscopy(SEM)showed that the nanocrystalline products were irregular long strip crystals.Transmission electron microscopy(TEM)showed that the size of geranyin nanoparticles was uniform.The dissolution rate of DSN-SN in vitro was significantly higher than that of the crude drug.Conclusion:DSN-Ns prepared with tea saponin as stabilizer is not only simple in preparation,but also can significantly improve the solubility and bioavailability of DSN,which provides reference for the development of multiple preparations of DSN.

关 键 词：香叶木苷 Box-Behnken响应面法 茶皂素 体外溶出度 

分 类 号：R283.2[医药卫生—中药学]