盐酸多柔比星脂质体注射液标准化释放度测定方法的建立

Development of a standardized method for in vitro release analysis of doxorubicin hydrochloride liposome injection

目的:探索并建立标准化盐酸多柔比星脂质体注射液释放度透析测定方法。方法:在《中华人民共和国药典》溶出度第一法——篮法的基础上设计并制作了适配于商品化透析膜管的转杆,使体外释放度透析测定法与溶出度仪相结合。在此装置上考察了释放介质、转速、膜材料、截留分子量和膜前处理方法对游离药物透膜速率的影响,建立并优化了盐酸多柔比星脂质体注射液释放度透析测定方法。用该方法测定盐酸多柔比星脂质体注射液的释放度。结果:建立的盐酸多柔比星脂质体注射液释放度透析测定方法标准化程度高,可操作性强,方法重复性和重现性较好,具有较强的普及性。该方法下测定的盐酸多柔比星脂质体体外释放曲线表现出120 h以上的缓释特征,更能反映本品的体内释放特点。结论:使用新装置建立的透析测定法可以用于盐酸多柔比星脂质体注射液释放度的标准化测定,也可为其他脂质体或微粒给药系统制剂释放度的标准化测定提供借鉴。

Objective: To explore and develop a standardized dialysis method for in vitro release analysis of a doxorubicin hydrochloride liposome injection. Methods: A novel shaft which can be assembled with commercial dialysis tube devices was designed and produced based on "the first method of dissolution"--basket method of the Chinese Pharmacopoeia( ChP). The dialysis method for in vitro release test was applied to dissolution apparatus equipped with the shaft. Using this new equipment,the dialysis method for in vitro release analysis was optimized by investigating the factors,including release media,stirring rate,membrane materials,molecular weight cut-off of membrane,and pretreatment of membrane,with regard to the influence on diffusion rate of free doxorubicin hydrochloride across the dialysis membrane. The in vitro drug release of doxorubicin hydrochloride liposome injection was finally determined and optimized by this dialysis method. The method was used to determine the release of doxorubicin hydrochloride liposome injection. Results: A dialysis method with high standardization,practicality,repeatability and reproducibility was developed for in vitro release analysis of doxorubicin hydrochloride liposome injection. The method showed good accessibility. The in vitro release curve of doxorubicin hydrochloride liposomes determined by this method showed profile of more than 120 h,which could better reflect the in vivo release characteristics of this product. Conclusion: The dialysis method established with the new equipment was able to be used for standardized in vitro release analysis of doxorubicin hydrochloride liposome injection,and also to be used as reference for standardized in vitro release analysis of other liposome and microparticle drug delivery systemformulations.