盐酸青藤碱柔性纳米脂质体的制备及质量考察

Studies on preparation and quality of flexible nano-liposome containing sinomenine hydrochloride

目的制备盐酸青藤碱柔性纳米脂质体,并研究其质量。方法用微柱离心法分离脂质体和游离药物,用HPLC法测定包封率。考察薄膜分散法、逆向蒸发法和pH梯度法对包封率的影响,并采用正交实验设计筛选盐酸青藤碱柔性纳米脂质体的最佳处方,测定其粒径。结果三种制备方法得到的药物脂质体的包封率大小依次为:pH梯度法>逆向法>薄膜法。正交实验设计中影响包封率的最显著因素为磷脂与胆酸钠的质量比,其次为外水相pH值,药脂比与孵育温度影响较小。最佳处方平均粒径128.4 nm,4℃放置30 d未产生聚积或沉淀。结论pH梯度法适合于制备盐酸青藤碱柔性纳米脂质体,工艺可行,产品质量稳定。

Objective To prepare and evaluate flexible nano-liposome of sinomenine hydrochloride （SM）. Method Three methods including film dispersion, reverse phase evaporation, and pH gradient method were compared during the preparation. Mini-column centrifugation was developed to separate liposome and free drug, and the entrapment efficiency was determined by HPLC. Orthogonal experimental design was applied to optimize formulation for SM flexible nano-liposome prepared by pH gradient method. The particle size was also investigated. Results The order of entrapment efficiency of SM flexible nano-liposome prepared by three methods was： pH gradient method〉 reverse phase evaporation〉 film dispersion. The entrapment efficiency of SM liposome was significantly affected by the ratio of SPC and sodium cholate, and which was also affected by the pH of external water phase to some extent; however, there was no obvious influence in term of the incubation temperature and the ratio of drug and SPC. The average particle size of optimal preparation was 128.4 nm, which was stable under the temperature of 4 ℃ for at least 30 days. No aggregation or deposition was observed. Conclusions The pH gradient method is suitable and feasible for the preparation of SM flexible nano-liposome,and the product is stable.