叶酸-聚乙二醇-阿霉素连接物及其制剂稳定性研究

The Stability of Folic Acid-Polyethylene Glycol(PEG)-hyd-Doxorubicin and Its Preparation

目的:考察叶酸-聚乙二醇-阿霉素连接物(FA-PEG-hyd-DOX)及其制剂在不同实验条件下的稳定性,为其开发应用奠定基础。方法:参照2010版《中国药典》二部附录XIXC《原料药与药物制剂稳定性试验指导原则》,将DOX、FA-PEG-hyd-DOX连接物原料及其冻干粉制剂置于高温、高湿、强光照环境中,不同时间对样品的DOX质量百分含量、熔点、外观性状等指标进行考察分析。结果:DOX在高温、高湿、强光照环境中放置10天后,DOX质量百分含量分别为31.95%、66.36%和61.27%,熔点分别为195℃、194℃和194℃。FA-PEG-hyd-DOX连接物在高温、高湿、强光照环境中放置10天后,DOX质量百分含量分别为2.71%、3.85%和3.14%,熔点范围分别为169-175℃、170-175℃和170-175℃。FA-PEG-hyd-DOX冻干粉制剂在高温、高湿、强光照环境中放置10天后,DOX质量百分含量分别为3.80%、5.76%和4.80%。结论:FA-PEG-hyd-DOX连接物原料的稳定性高于DOX,FA-PEG-hyd-DOX甘露醇冻干粉制剂的稳定性高于其原料药。

Objective： To investigate the stability of the folic acid-polyethylene glycol-doxorubicin conjugate（FA-PEG-hyd-DOX）and its pharmaceutical preparations in different experimental conditions,and to lay the foundation for the research and development of FA-PEG-hyd-DOX. Methods： According to the second appendix XIXC in Chinese Pharmacopoeia（2010 edition, the guidance of active pharmaceutical ingredients and pharmaceutical preparation stability test）, the stability of DOX, FA-PEG-hyd-DOX conjugate and FA-PEG-hyd-DOX pharmaceutical preparation were studied at the environment of high temperature, high humidity and strong illumination. Meanwhile, the content of DOX, melting point and external characteristics were determined as stability index. Results： After DOX was placed at the environment of high temperature, high humidity and strong illumination for 10 days, the content of DOX was 31.95 %,66.36 % and 61.27 % respectively, and its melting point was 195 ℃, 194 ℃ and 194 ℃ respectively. After FA-PEG-hyd-DOX conjugate was placed at the environment of high temperature, high humidity and strong illumination for 10 days, the content of DOX was 2.71 %,3.85 % and 3.14 % respectively, and its melting point was 169-175 ℃, 170-175 ℃ and 170-175 ℃ respectively. After FA-PEG-hydDOX pharmaceutical preparation was placed at the environment of high temperature, high humidity and strong illumination for 10 days,the content of DOX was 3.80 %, 5.76 % and 4.80 % respectively. Conclusions： The stability of FA-PEG-hyd-DOX was better than that of DOX, and the stability of FA-PEG-hyd-DOX pharmaceutical preparation was better than that of FA-PEG-hyd-DOX conjugate.