目的 研制紫杉醇自微乳并进行质量评价。方法 考察紫杉醇在不同油相、乳化剂和助乳化剂中的溶解度, 再通过滴制法绘制伪三元相图, 确定最优的Km值和处方, 制备紫杉醇自微乳;并考察自微乳的外观、形态、粒径、载药量和稳定性。结果 以聚氧乙烯蓖麻油EL35-卵磷脂/无水乙醇/中碳链甘油酯/水形成了均匀稳定的系统;紫杉醇自微乳为淡黄色澄明液体, 稳定, 平均粒径19.4 nm, 呈Gauss分布, 透射电镜下成圆球形, 分布均匀。自微乳经0.9%的氯化钠注射液和5%的葡萄糖注射液稀释10及50倍后, 外观、pH值、载药量、粒径均无明显变化。结论 紫杉醇自微乳易于制备、质量稳定, 为紫杉醇新型制剂的研发提供了科学依据。
Abstract
OBJECTIVE To prepare paclitaxel self-microemulsifying drug delivery system(PTX-SMEDDS)and evaluate its quality. METHODS The equilibrium solubility of paclitaxel in different compositions of oil, emulsifiers and assistant emulsifiers was investigated. The optimal Km was determined and PTX-SMEDDS was prepared by using the method of titration to establish the pseudo-ternary phase diagram. The appearance, morphology, size distribution, concentration and stability of PTX-SMEDDS were determined. RESULTS PTX-SMEDDS prepared with EL-35, lecithin and anhydrous ethanol at the ratio of 4∶1∶6, containing 6% DOC-Na and 7.5% of MCT, was a uniform and stable colloidal system displaying as a translucent diluted-yellow solution. PTX-SMEDDS under electron microscopy consisted of small spherical drops with a mean diameter of 19.4 nm. The appearance, pH, concentration and particle size of SMEDDS were stable after it was diluted with sodium chloride injection and glucose injection by 10-fold or 50-fold, respectively.CONCLUSION The PTX-SMEDDS is easy to prepare and its quality is stable, which provieds some information for the development of new paclitaxel formulations.
关键词
紫杉醇 /
自微乳释药系统 /
伪三元相图 /
制备 /
质量评价
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Key words
paclitaxel /
self-microemulsifying drug delivery system /
pseudo-temary phase diagram /
preparation /
quality evaluation
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中图分类号：
R944
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参考文献
[1] YOSHIZAWA Y, KONO Y, OGAWARA K, et al. PEG Liposomalization of paclitaxel improved its in vivo disposition and antitumor effcacy. Int J Pharm, 2011, 412(1-2):132-141.[2] DOSIO F, STELIA B, ARPICCO S, et al. Macromolecules as taxane delivery systems. Expert Opin Drug Deliv, 2011, 8(1):33-55.[3] YANG E C, LI C Q, LIN C Z, et al. Reaearch progress on improving the poor solubility for paclitaxel. Cent South Pharm(中南药学), 2011, 9(8):615-618.[4] LIU Y, ZHANG P, PENG N, et al. Optimization and in situ intedtinal absorption of self-microemulsifying drug delivery system of oridonin. Int J Pharm, 2009, 365(1-2):136-142.[5] ZHANG X J, WANG D K, YAO J M, et al. Formulation optimization and chemical stability study of self-microemulsified tanshinone ⅡA emulsion for injection . Chin J Pharm(中国药剂学杂志), 2010, 8(5):117-125.[6] QUAN D Q, GE M, GAO L J. Langmuir-blodgett film technology for formulation studies on self-microemulsifying drug delivery system (SMEDDS) . Chin Pharm J(中国药学杂志), 2012, 47(12):1001-1003.[7] ZHOU L J, LIU Q F, CHEN X, et al. Preparation and quality evaluation of paclitaxel microemulsion by dispersionmethod. J Chin Pharm(中国药房), 2010, 21(23):2139-2141.[8] ANSARI K A, TORNE S J, VAVIA P R, et al. Paclitaxel loaded nanosponges:In-vitro characterization and cytotoxicity study on MCF-7 cell line culture. Curr Drug Deliv, 2011, 8(2):194-202.[9] FENG J, WU D, ZHOU W B, et al. Progress of clinical research on new nano-drug delivery system of paclitaxel. Chin Arch Chin Med(中华中医药学刊), 2012, 30(10):2021-2023. ZHOU L J, LIU Q F, CHEN X, et al. In vivo pharmcokinetics and distribution of nimodipine microemulsion injection in mice. Chin J New Drugs(中国新药杂志), 2009, 18(13):1231-1236.
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脚注
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基金
国家自然科学基金资助项目(30500666);清华大学-裕元基金(20240000548)
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