PDF《苦参碱自微乳化制剂的制备工艺研究》

苦参碱自微乳化制剂的制备工艺研究 李洪松

1 ,张学顺 2* ,付春生

2 ,冯静11.

山东中医药大学药学院,山东 济南

250355 2. 山东中医药大学附属医院,山东 济南

250011 摘要:目的 研制苦参碱自微乳制剂,并对其进行质量评价.方法 通过溶解度试验、伪三元相图的研究,筛选出苦参碱 自微乳最佳处方;

在此基础上制备苦参碱自微乳制剂,建立 HPLC 法测定自微乳中苦参碱的方法;

对自微乳的外观、形态、 粒径及其分布、Zeta 电位、载药量和稳定性进行考察.结果 苦参碱自微乳最佳处方为苦参碱-油酸-油酸乙酯-EL-40-异丙醇 (0.5∶0.15∶0.15∶0.35∶0.35) ;

制备的苦参碱自微乳为澄明液体,流动性、稳定性好,遇水形成 O/W 型微乳,平均粒径

68 nm.载药量为 42.689 mg/mL.结论 自微乳制剂制备工艺简单,性质稳定,为苦参碱自微乳制剂的进一步研究奠定基础. 关键词:苦参碱;

自微乳制剂;

伪三元相图;

HPLC;

O/W 型微乳 中图分类号:R283.6 文献标志码:A 文章编号:0253 - 2670(2013)04 -

0 -

0 Research on preparation process of matrine self-microemulsifying drugs LI Hong-song1 , ZHANG Xue-shun2 , FU Chun-sheng2 , FENG jing1 1. Shandong University of Traditional Chinese Medicine, Jinan 250355, China 2. Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China Abstract: Objective To develop the matrine self-microemulsifying drug syetem (SMEDDS) and evaluate its quality. Methods The solubility test and pseudo-ternary phase diagram were utilized to select proper matrine microemulsions prescription. On this basis, matrine SMEDDS was formulated and HPLC method was used to determine drug content in matrine SMEDDS;

the appearance, morphology, particle size, particle size distribution, Zeta potential drug loading, and stability of matrine SMEDDS of self- microemulsifying were studied. Results The best prescription of matrine SMEDDS was matrine-oleic-ethyloleate-EL-40-isopropanol (0.5∶0.15∶0.15∶0.35∶0.35). The selected matrine SMEDDS was transparent liquid, and good liquidity and stability, and with water to form O/W type microemulsion, with an average particle size of

68 nm. The drug loading was 42.689 mg/mL. Conclusion The self-microemulsifying technology was simple, stable, and provides a strong foundation for research of Matrine SMEDDS drug. Key words: matrine;

self-microemulsifying;

pseudo-ternary phase diagram;

HPLC;

O/W type microemulsion 苦参碱是豆科植物苦参、苦豆子及广豆根中主 要的生物碱之一,属四环喹嗪啶类生物碱.近年来 大量药理和临床作用研究发现,苦参碱具有抗肝纤 维化、抗心律失常、免疫抑制、抗炎、抗高血压血 管重构、抗肿瘤等多种药理作用[1] .苦参碱的消除 半衰期较短,不易溶于水,且随水温升高溶解度降 低,普通片剂、胶囊等口服后溶出速率慢,吸收较 差,生物利用度低[2] . 自微乳化给药系统(self-microemulsifying drug delivery system,SMEDDS)[3] 是由药物、油相、乳 化剂和助乳化剂组成的均一透明的液体,为热力学 稳定的混合体系,可灌装成软胶囊或压制成片[4] . 口服后在胃肠的蠕动下遇水分散而自发形成粒径小 于100 nm 的微乳溶液,形成的乳滴由于具有很大 的表面积,能增加难溶性药物的释放和吸收,提高 口服生物利用度[5-7] .本实验旨在制备苦参碱 O/W 型自乳化微乳制剂,以期使其具有一定的缓释性和 靶向作用,减少临床不良反应,提高药物疗效.