达比加群酯纳米乳的制备及体外评价  

Preparation and in vitro evaluation of dabigatran etexilate nanoemulsion

作　　者：张雅捷 刘晓庆 陈敏 柴夫娟 郑春丽[1] 刘建平[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]上海市浦东新区周浦医院药剂科,上海201318

出　　处：《中国药科大学学报》2016年第6期688-693,共6页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81402878);中央高校基本科研业务项目资助项目(No.2015PT050);上海浦东新区科技发展基金资助项目(No.PKJ2015-Y41)~~

摘　　要：为改善难溶弱碱性药物达比加群酯的生物利用度,制备达比加群酯水包油型纳米乳并对其进行体外质量评价。通过测定达比加群酯在油性溶媒中的溶解度和绘制伪三元相图筛选出油相、乳化剂和助乳化剂;在此基础上以粒径和稳定性为评分指标,采用正交试验设计进一步优化达比加群酯纳米乳的处方和工艺。对达比加群酯纳米乳的形态、粒径、Zeta电位、包封率和稳定性进行考察。实验结果为:达比加群酯纳米乳系统为油酸/中链甘油三酯/聚氧乙烯氢化蓖麻油/乙二醇单乙基醚/水;该纳米乳的粒径为(57.5±0.2)nm、电位为-(20.9±1.4)mV、包封率为(85.2±1.0)%,且在室温下储存3个月后,其粒径、稳定常数和药物含量均未发生显著变化。结果表明:通过处方和工艺的优化后,可制备得到澄清透明、粒径均一、稳定性良好的达比加群酯纳米乳,这为提高达比加群酯及其他难溶碱性药物的生物利用度提供了新的研究思路。The purpose of this study was to prepare dabigatran etexilate nanoemulsion to improve bioavailability of dabigatran etexilate, a poorly water-soluble drug. The physicochemical properties and the stability of dabigatran etexilate nanoemulsion were investigated. Equilibrium solubility of dabigatran etexilate in commonly used oil materials for nanoemulsion were determined for selection. Then, surfactant and co-surfactant were chosen based upon the plooted pseudo-ternary diagrams. The formulation and preparation process were further optimized with orthogonal design. As a result, the dabigatran etexilate nanoemulsion was formulated based on the system consisting of Oil Acid/Labrafac Lipophile WL1394/Cremophor RH40/Transcutol P/H2O. The dabigatran etexilate nanoemulsion was found to have a mean diameter of（57. 5±0. 2）nm, Zeta potential of -（20. 9±1. 4）mV, and the drug encapsulation efficiency of（85. 2±1. 0）%. Besides, the droplet size, stability constant and drug content of the nanoemulsion was found to have no significant changes in at least 3 months under room temperature. In conclusion, the uniform and stable dabigatran etexilate nanoemulsion with a clear and translucent appearance was obtained after the optimization of formulation and preparation process. Thus nanoemulsion could be a promising way for the improvement of bioavailability of dabigatran etexilate and other poorly water-soluble drugs.

关 键 词：达比加群酯 纳米乳 伪三元相图 正交设计 难溶弱碱性药物 体外评价 

分 类 号：R943[医药卫生—药剂学]