主动载药法制备盐酸去氢骆驼蓬碱脂质体.doc

主动载药法制备盐酸去氢骆驼蓬碱脂质体 杜松 邓英杰 张威 沈阳药科大学药学院,，辽宁，沈阳 110016 摘要： 目的：制备高包封率的盐酸去氢骆驼蓬脂质体。 方法：采用pH梯度法进行主动载药。进行了处方前研究，测定了药物在不同pH值的缓冲液中溶解度及表观油水分配系数，为脂质体合理设计提供参考。采用柠檬酸缓冲溶液制备空白脂质体，碳酸钠调节外相至中性造成pH梯度，进行主动载药。采用超滤法分离脂质体与游离药，测定包封率。考察了药脂比、孵化温度、外水相pH 值对包封率的影响。 结果：随pH值的增大，盐酸去氢骆驼蓬碱的溶解度降低，油水分配系数增大。采用主动载药法，在药脂比（w/w）: 杜松(1975--)，男，，博士生，从事科研工作。???Tel：(024) 23?E-mail：dPreparation of harmine hydrochloride liposomes by active loading method Du Song, Deng Ying-jie, Zhang Wei ( School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016 , China) ABSTRACT : OBJECTIVE:The aim of this study was to prepare a harmine hydrochloride liposomes formulation with high entrapment efficiency. METHODS: Harmine hydrochloride was encapsulated into liposomes by active loading method to get high entrapment efficiency. Preformulation test was carried for rational design. Soulibilities and partition coefficient of harmine in buffer of different pH was determined. Empty liposome is prepared with citrate buffer solution, and extravesicular pH was alklined to neutral by sodium carbonate solution. Harmine hydrochloride was encapsulated into liposomes by pH gradient. Encapsulation efficiency was determined after the free drug was separated from liposome by ultrafiltration. The influences factors on the entrapment efficiency including drug to lipid weight ratio, incubation temperature, pH of external water phase were investigated. RESULTS:　 As the pH value increasing, the soulibility of harmine was decreased, while the partition coefficient is increased. By active loading method, the entrapment efficiency could be more than 80% when the drug/lipid weight ratio was under 0.3. The pH gradient between intervesicle and intravesicle obviously influence the entrapment efficiency, while incubation temperature have little effect on entrapment efficiency. CONCLUSION: Active loading is suitable for preparing harmine hydrochloride liposome with high entrapment efficiency. KEY WORDS: harmine hydrochloride; liposom