星点设计-效应面法优化基于甘草酸的葛根素纳米乳及其体外释放研究  

Optimization of puerarin nanoemulsion based on glycyrrhizic acid by central composite design-response surface method and its in vitro release studies

作　　者：张琳琳 李小芳[1] 谢龙 宋佳文 廖艳梅 仲粒 ZHANG Lin-lin;LI Xiao-fang;XIE Long;SONG Jia-wen;LIAO Yan-mei;ZHONG Li(College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Key Laboratory of Standardization of Chinese Herbal Medicine,Ministry of Education,Key Laboratory of Systematic Research,Development and Utilization of Chinese Medicine Resources in Sichuan Province,State Key Laboratory Breeding Base of Co-founded by Sichuan Province and Ministry of Science and Technology,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院中药材标准化教育部重点实验室四川省中药资源系统研究与开发利用重点实验室省部共建国家重点实验室培育基地,四川成都611137

出　　处：《中草药》2020年第12期3180-3186,共7页Chinese Traditional and Herbal Drugs

基　　金：四川省科技厅科研项目(2019YFS0113);国家中医药管理局项目(2018ZY03002)。

摘　　要：目的以甘草酸为天然稳定剂制备葛根素纳米乳(Pue-NE),并考察其体外释放特性。方法采用高速剪切联合高压均质法制备Pue-NE,以平均粒径和多分散指数(PDI)为自变量,运用总评归一值(OD)为评价指标进行数据处理,采用星点设计-效应面法优化处方,并对最优处方制备的Pue-NE进行理化性质和释放特性考察。结果Pue-NE的最佳处方为葛根素质量浓度5.0 mg/mL,甘草酸质量浓度1.75 mg/mL,辛癸酸甘油酯用量3.5 mL。Pue-NE平均粒径为(184.5±0.8)nm、PDI为0.088±0.002、Zeta电位为(10.56±0.35)mV、电导率为(98.3±0.4)μs/cm、pH为6.750±0.005、溶解度为(4.970±0.008)mg/mL、载药量为(99.4±0.2)%,浊度为(24.3±1.0)cm−1(n=3)。经染色法鉴别为O/W型乳液,透射电镜扫描结果显示液滴呈大小均匀的圆球形。稳定性结果表明,Pue-NE在25℃条件下,储存稳定性良好。体外释放结果表明,24 h内Pue-NE在pH 6.8的磷酸盐缓冲液中释放度最大。结论以甘草酸为天然稳定剂制备Pue-NE不仅制备方法简便,还可有效替代传统化学合成稳定剂的使用,改善葛根素的溶解性。Objective Puerarin nanoemulsion(Pue-NE)was prepared with glycyrrhizic acid as a natural stabilizer,and its release characteristics in vitro were investigated.Methods Data processing was performed using particle size and polydispersity index(PDI)as independent variables,and using the overall desirability(OD)as the evaluation index.The central composite design-response surface method was used to optimize the prescription,and the physical and chemical properties and release characteristics of Pue-NE prepared by the optimal prescription were investigated.Results The best prescription for Pue-NE is puerarin at a concentration of 5.0 mg/mL,glycyrrhizic acid at a concentration of 1.75 mg/mL,and caprylic glyceride in an amount of 3.5 mL.The average particle size of the nanoemulsion is(184.5±0.8)nm,the PDI is 0.088±0.002,the zeta potential is(10.56±0.35)mv,the conductivity is(98.3±0.4)μs/cm,pH is 6.750±0.005,solubility(4.970±0.008)mg/mL,drug loading is(99.4±0.2)%,turbidity(24.3±1.0)cm−1(n=3).It was identified as O/W emulsion by dyeing method.TEM scanning results show that the droplets are spherical and uniform in size and the stability results showed that Pue-NE has good storage stability at 25℃.In vitro release results showed that Pue-NE has the greatest release in phosphate buffered pH 6.8 within 24 hours.Conclusion The preparation of Pue-NE with glycyrrhizic acid as a natural stabilizer is not only simple and convenient,but also can effectively replace the use of traditional chemical synthetic stabilizers and improve the solubility of puerarin.

关 键 词：纳米乳 葛根素 甘草酸 天然稳定剂 星点设计-效应面法 总评归一法 体外释放 高速剪切联合高压均质法 浊度 溶解度 O/W型乳液 稳定性 

分 类 号：R283.6[医药卫生—中药学]