摘要
目的制备一种紫杉醇-白桦脂酸混合纳米混悬剂,优化制备工艺。方法采用高压均质法,以泊洛沙姆188、卵磷脂为稳定剂,以稳定剂浓度、稳定剂比例、均质压力、循环次数为考察因素,以粒径及PDI为评价指标,采用星点设计-效应面法优化处方,并对其进行体外评价。结果最优工艺为稳定剂质量浓度0.6mg/m L,泊洛沙姆188-卵磷脂(2∶1),均质压力100 MPa,循环次数20次。最优工艺制备的纳米混悬剂平均粒径为(282.54±5.40)nm,PDI为0.242±0.020。紫杉醇-白桦脂酸混合纳米混悬剂中药物粒子呈棒状,再分散性与短期稳定性均良好,其中的紫杉醇和白桦脂酸均以无定形形式存在。制备成纳米冻干粉后,紫杉醇水中溶解度提高约90倍,白桦脂酸提高约100倍。在2h内纳米冻干粉中2种药物累积溶出百分率显著提高,均达到95%。结论采用星点设计-效应面法优化纳米混悬剂制备工艺是有效、可行的,纳米混悬剂可改善紫杉醇和白桦脂酸溶出。
Objective To prepare compounded nanosuspensions of paclitaxel and betulinic acid nanosuspension and optimize the preparation process.Methods Nanosuspension was prepared by high pressure homogenization with poloxamer 188 and lecithin as stabilizer.Stabilizer concentration,stabilizer ratio,homogeneous pressure,and cycle times were selected as investigation factors and the particle size and PDI of nanosuspension were selected as evaluation index to optimize the prescription by Box-Behnken design-response surface method and the in vitro evaluation was determined.Results The optimal formulation was as follows:stabilizer concentration 0.6 mg/mL,poloxamer 188-lecithin(2∶1),homogenous pressure 100 MPa,cycle times 20 times.The average particle size was(282.54±5.40)nm,PDI was 0.242±0.020.The nano-particles in the paclitaxel-betulinic acid compounded nanosuspension were rod-shaped.The nanosuspension had perfect redispersibility and satisfactory short-term stability.Paclitaxel and betulinic acid in nano lyophilized powders all existed in amorphous form.After being prepared into nanosuspension formulation,the solubility of paclitaxel in water was increased by about 90 times while that of betulinic acid was increased by about 100 times.In 2 h,the cumulative dissolution rate of paclitaxel and betulinic acid in nanosuspension of paclitaxel and betulinic acid were all up to 95%.Conclusion Optimizing the preparation process of nano-suspension with Box-Behnken design-response surface method is effective and feasible and nanosuspension formulation can improve the dissolution of paclitaxel and betulinic acid observably.
作者
蒋爱
李国源
王鑫
崔小兵
李俊松
狄留庆
JIANG Ai;LI Guo-yuan;WANG Xin;CUI Xiao-bing;LI Jun-song;DI Liu-qing(College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Engineering Research Center for Efficient Delivery System of TCM,Nanjing 210023,China)
出处
《中草药》
CAS
CSCD
北大核心
2019年第4期852-859,共8页
Chinese Traditional and Herbal Drugs
关键词
紫杉醇
白桦脂酸
纳米混悬剂
星点设计
效应面法
paclitaxel
betulinic acid
nanosuspension
Box-Behnken design
response surface method
