穿心莲内酯自纳米乳处方优选及沉淀抑制剂对其分散相行为的影响  

Formulation optimization of andrographolide self-nanoemulsifying drug delivery system and effect of precipitation inhibitor on its phase behavior

作　　者：丁海波 赖章婷 陈绪龙 袁其里 欧阳料淇 刘欢 廖正根 DING Hai-bo;LAI Zhang-ting;CHEN Xu-long;YUAN Qi-li;OU YANG Liao-qi;LIU Huan;LIAO Zheng-gen(Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of TCM,Nanchang 330004,China)

机构地区：[1]江西中医药大学,现代中药制剂教育部重点实验室,江西南昌330004

出　　处：《中草药》2020年第16期4160-4168,共9页Chinese Traditional and Herbal Drugs

基　　金：江西省一流学科资助(JXSYLXK-ZHYAO059)。

摘　　要：目的研究羟丙基甲基纤维素(hydroxypropyl methyl cellulose,HPMC)、聚乙烯吡咯烷酮k30(polyvinylpyrrolidone k30,PVP k30)、聚乙二醇4000(polyethylene glycol 4000,PEG 4000)对穿心莲内酯自纳米乳(AG-SNEDDS)在人工肠液中分散相行为的影响。方法采用星点设计优选AG-SNEDDS处方;以过饱和度为指标,考察PVP k30、HPMC、PEG 40003类沉淀抑制剂(PPI)对AG-SNEDDS在人工肠液中分散后过饱和行为的影响,并用偏振光显微镜考察沉淀类型。结果 AG-SNEDDS处方为丙二醇单辛酸酯(propylene glycol caprylate,Capryol 90)-[聚氧乙烯蓖麻油(polyoxyethylene castor oil,Cremophor EL)-聚山梨酯-20(polysorbate 20,Tween-20)(1∶1)]-二乙二醇单乙基醚(diethylene glycol monoethyl ether,Transcutol HP)质量比为12.9∶40.5∶46.6;形成的乳剂均一透明,载药量为(6.93±0.04)mg/mL,乳化时间为(22.33±0.33)s,平均粒径为(14.25±0.65)nm。HPMC、PEG4000能维持AG-SNEDDS的肠液分散后的过饱和,且作用效果与用量呈正相关;PVP k30低浓度时降低AG-SNEDDS的肠液分散后的过饱和,中、高浓度时可维持过饱和。3种沉淀抑制剂均使沉淀颗粒粒径减小。结论沉淀抑制剂能维持穿心莲内酯自纳米乳在人工肠液中分散时的过饱和,维持过饱和的能力因沉淀抑制剂的类型和用量而不同。Objective To investigate the effect of HPMC, PVP k30 and PEG 4000 on the phase behavior of andrographolide self-nanoemulsifying drug delivery system(AG-SNEDDS) dispersed in Fasted-state simulated intestinal fluid(FaSSIF). Methods The preparation technology of andrographolide AG-SNEDDS was optimized by central composite design. The effect of three types of precipitation inhibitors(PVP-k30, HPMC, PEG 4000) on the supersaturation behavior of AG-SNEDDS dispersed in FaSSIF was investigated with the degree of supersaturation as an evaluation index. The precipitated phase was evaluated by polarized light microscopy(PLM). Results The results showed that the best prescription of AG-SNEDDS was Capryol 90-Cremophor EL:Tween-20(1∶1)-Transcutol HP(12.9∶40.5∶46.6). The self-microemulsion was uniform, the drug loading was(6.93 ± 0.04) mg/g. The emulsification time was(22.33 ± 0.33) s, the average particle size was(14.25 ± 0.65) nm. HPMC and PEG 4000 can maintain the supersaturation of AG-SNEDDS after being dispersed in FaSSIF, and the effect was positively correlated with their concentration. As for PVP k30, it reduced the degree of supersaturation at a low concentration, but can maintain supersaturation at medium and high concentration. Using any of the three precipitation inhibitors can reduce the particle size of the precipitated particles. Conclusion Precipitation inhibitors can maintain the supersaturation of AG when disperse AG-SNEDDS in FaSSIF. The ability to maintain supersaturation varies with the types and concentration of precipitation inhibitor.

关 键 词：穿心莲内酯 星点设计 自纳米乳药物递送系统 过饱和 沉淀抑制剂 

分 类 号：R283.6[医药卫生—中药学]