http://jcps.bjmu.edu.cn

• 研究论文 • 上一篇    下一篇

9-硝基喜树碱自微乳化注射液的研制及其体内药动学行为

吕娟丽, 王坚成*, 张烜, 张强*   

  1. 1. 北京大学药学院 药剂学系, 北京 100083;
    2. 北京大学 天然药物与仿生药物国家重点实验室, 北京 100083;
    3. 武警总医院药剂科, 北京 100039
  • 收稿日期:2007-05-09 修回日期:2007-08-10 出版日期:2007-09-15 发布日期:2007-09-15
  • 通讯作者: 王坚成*, 张强*

Preparation and characterization of 9-nitrocamptothecin self-emulsifying microemulsion injection

Juan-Li Lu, Jian-Cheng Wang*, Xuan Zhang, Qiang Zhang*   

  1. 1. Deparment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China;
    2. The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China;
    3. Department of pharmacy, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China
  • Received:2007-05-09 Revised:2007-08-10 Online:2007-09-15 Published:2007-09-15
  • Contact: Jian-Cheng Wang*, Qiang Zhang*

摘要:

目的 制备9-硝基喜树碱自微乳化静脉注射给药系统 (9-NC ME), 并考察其在大鼠体内的药动学情况。方法 采用伪三元相图确定油相制剂组成, 以正交设计优化处方组成, 评价了9-NC ME制剂的稳定性, 并考察了正常大鼠尾静脉注射后体内的药动学行为。结果 以注射用大豆油为油相、EPC/Tween 80为乳化剂、无水乙醇为助乳化剂等成分组成的新型注射剂9-NC ME, 在临用前用5%葡萄糖注射液稀释20倍后可自发形成平均粒径38.3 ± 4.0 nm 稳定微乳, 大鼠尾静脉给予 9-NC ME药动学参数为: t1/2 (0.97 ± 0.14 h), AUC0-∞ (372.77 ± 49.62 ng·h·mL-1) and MRT (1.40 ± 0.21 h), 分别是对照溶液剂的1.41.651.4(P<0.01)结论 9-NC ME 具有较好的物理和化学稳定性, 有望成为新型的9-NC静脉注射剂。

关键词: 9-硝基喜树碱, 9-硝基喜树碱, 9-硝基喜树碱, 自微乳化给药系统, 自微乳化给药系统, 自微乳化给药系统, 静脉注射, 静脉注射, 静脉注射, 药动学, 药动学, 药动学

Abstract:

Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin (9-NC ME) for intravenous injection and investigation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1:20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, AUC0-∞ of 372.77 ± 49.62 ng·h·mL-1, and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution (P<0.01). Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.

Key words: 9-Nitrocamptothecin, 9-Nitrocamptothecin, Self-emulsifying microemulsion, Self-emulsifying microemulsion, Injection, Injection, Pharmacokinetics, Pharmacokinetics

中图分类号: 

Supporting:

Foundation item: National Natural Science Foundation of China (Grant No.30430760) and the 985 projects (Phase II) of the State Key Laboratory of Natural and Biomimetic Drugs (Peking University, China).
*Corresponding authors.
Jian-Cheng Wang, Ph.D, Tel./fax: 86-10-82802683;
Qiang Zhang, Prof., Tel./fax: 86-10-82802791