蒿甲醚口服微乳原位凝胶的制备与评价  

Preparation and Evaluation of Artemether Oral Microemulsion-in situ Gel

作　　者：薛鸿娇 唐华争 张琪 郭坤坤 杨兆祥 蔡铮 XUE Hong-jiao;TANG Hua-zheng;ZHANG Qi;GUO Kun-kun;YANG Zhao-xiang;CAI Zheng(Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China;Institute of Pharmaceutical Research, KPC Pharmaceuticals Inc. , Kunming 650100, China)

机构地区：[1]南方医科大学药学院广东省新药筛选重点实验室,广州510515 [2]昆药集团股份有限公司药物研究院,昆明650100

出　　处：《中国实验方剂学杂志》2018年第9期29-36,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广东省自然科学基金项目(2016A030313562)

摘　　要：目的：优选蒿甲醚口服微乳原位凝胶的处方,并对其性质进行评价。方法：以流动性和凝胶性为指标筛选水相,通过溶解度、相溶性、制剂稳定性和黏附性的考察确定处方组分,采用伪三元相图筛选微乳原位凝胶区域,优选蒿甲醚微乳原位凝胶的最优处方,并对其形态,粒径,Zeta电位,黏度,稳定性,凝胶性以及体内胃滞留时间进行评价。结果：蒿甲醚微乳原位凝胶的最优处方为蒿甲醚-三乙酸甘油酯-聚氧乙烯蓖麻油-二乙二醇单乙基醚-（0.3%结冷胶-0.1%低黏度海藻酸钠）（0.5∶4.5∶5∶5∶85）,药物浓度约5 g·L^（-1）,透射电镜下观察乳滴呈球形,平均粒径20.90 nm,多分散指数（PDI）0.172,Zeta电位-19.5 mV,黏度15.32 m Pa·s,在室温条件下稳定。大鼠口服蒿甲醚微乳原位凝胶后,微乳原位凝胶在胃中快速发生相变形成凝胶,6 h后依然能在大鼠的胃中观察到凝胶并检测出蒿甲醚。结论：蒿甲醚微乳原位凝胶改善了蒿甲醚的溶解度,在胃部凝胶性能良好,能有效延长蒿甲醚的胃滞留时间,且黏度适宜,适合口服给药。Objective：To screen the optimal formula for artemether oral microemulsion-in situ gel and evaluate its properties.Method：With liquidity and gelation capacity as indexes,the water phase was determined.The composition was screened by solubility assay,compatibility test,stability and adhesiveness of microemulsion-in situ gel system.Pseudoternary phase diagram was used to optimize the formula.The morphology,particle size,Zeta potential,viscosity,stability,gelation and gastric retention time in vivo of artemether microemulsion-in situ gel were investigated,respectively.Result：The optimal formula was as follows：artemether ∶ glyceryl triacetate ∶ cremophor EL35 ∶ transcutol HP ∶（0.3% gellan gum-0.1% sodium alginate with low viscosity） = 0.5 ∶ 4.5 ∶ 5 ∶ 5 ∶ 85,the concentration of artemether in the microemulsion-in situ gel about 5 g·L（-1）.Artemether microemulsion-in situ gel in transmission electron microscope consisted of small spherical droplets,mean particle size,polydispersity index（PDI）,Zeta potential,viscosity of the drug delivery system were 20.90 nm,0.172,-19.5 mV and 15.32 m Pa·s,respectively.After oral administration,it gelled in the stomach of rats immediately; six hours later,gel could still be observed and artemether could be detected in the stomach.Conclusion：The solubitily of artemether is significantly increased in microemulsion-in situ gel.The artemether microemulsion-in situ gel has characteristics of good gelation in stomach and suitable viscosity,it not only can prolong the gastric retention time of artemether but also is suitable for oral administration.

关 键 词：蒿甲醚 微乳 原位凝胶 口服给药 伪三元相图 胃滞留时间 结冷胶 

分 类 号：R22[医药卫生—中医基础理论] R289[医药卫生—中医学]