小粒径盐酸阿霉素白蛋白微球的研制及其含量测定

Preparation of small particle size of doxorubicin hydrochloride albumin microspheres and determination of doxorubicin content by HPLC

目的 研制出适宜于静脉注射的小粒径盐酸阿霉素白蛋白微球。方法 采用常温乳化 -化学交联法 ,用正交实验筛选出最佳工艺 ,并对影响因素进行考察 ;建立HPLC -UV法测定其含量及包封率 ,用动态透析法研究其释放度。结果 用该工艺制备出的盐酸阿霉素微球粒径小 ,方法简便 ,反应条件容易控制。制备的微球均匀圆整 ,平均粒径约为 2 μm ,包封率为 82 .87% ,载药量为 9.2 5 %。体外释放表明其具有明显的缓释功能。HPLC -UV法检测盐酸阿霉素含量方法简便、准确 ,含量测定线性范围为 0 .5～ 5 .0 μg·ml-1(r =0 .9992 ) ,平均回收率为 99.16 %± 0 .97%。结论 采用常温乳化 -化学交联法可制备出适宜于静脉注射的小粒径微球 。

Aim To prepare doxorubicin hydrochloride albumin microspheres with small particle size for intravenous injection.Methods An optimal process was established by orthogonal test for preparation albumin microspheres with the method of emulsification at ambient temperature- chemical cross-linking. The factors that affect the particle size and release rate in vitro were studied.HPLC method was established for determination of content of doxorubicin in albumin microspheres.Results The prepared albumin microspheres of doxorubicin had a small particle size and the process was easy to control.The mean diameter of microspheres was 2μm and the entrapment efficiency 82.87%.The content of doxorubicin in the albumin microspheres was 9.25%.The release rate of doxorubicin in vitro showed that the albumin microspheres had pronouncedly sustained-release effect.Calibration curve was constructed in the concentration range 0.5～5.0μg·ml -1 (r=0.999 2).The average recovery was 99.16%±0.97%.Conclusion The established process with the method of emulsification at ambient temperature- chemical cross-linking is suitable for preparing smaller particle size microspheres for intravenous injection,thus avoiding greater particle sizes of microspheres that are prepared with the commonly-used method.