摘要
制备坦西莫司脂质体冻干剂,优化其处方及工艺,并进行大鼠药代动力学研究。用薄膜分散法制备坦西莫司脂质体,采用冷冻干燥法制备脂质体冻干剂,单因素实验考察最佳处方为:磷脂浓度24 mg/mL,药物与磷脂质量比1∶40,磷脂与胆固醇质量比10∶1,冻干保护剂蔗糖与磷脂的质量比2∶1。复溶后粒径(100.8±6.74)nm,包封率(95.24±3.58)%。透析法研究脂质体的体外释放行为,37℃下,在pH 7.4的磷酸盐缓冲液中24 h释放不到30%。用高效液相色谱法研究最佳处方脂质体的大鼠药代动力学,其最高血药浓度为市售制剂Torisel的3.06倍,生物利用度为Torisel的2.49倍。实验结果显示,经过处方工艺优化后的坦西莫司脂质体冻干剂包封率较高,具有缓释效果,可以显著提高坦西莫司在大鼠体内的生物利用度。
Lyophilized temsirolimus-loaded liposomes were prepared; the formulations were optimized; and the pharmacokinetics in rats was investigated. The lyophilized temsirolimus-loaded liposomes were prepared by film dispersion, followed by freeze drying. Formulations were optimized by single-factor design. The optimized formula- tion contained 24 mg/mL phosphatidyl choline（PC）, a weight ratio of 1 ： 40 between drug loading and PC, and a weight ratio of 10 ： 1 between PC and cholersterol. Sucrose was determined as an optimal lyoprotectant, and the weight ratio between sucrose and PC was 2 ： 1. The optimized liposomes had a particle size of （ 100. 8 ± 6.74） nm and an entrapment efficiency of （95.24 ± 3.58） %. Dialytic method was used to investigate the drug release pro- file. Less than 30% of entrapped drug was released after 24 h at pH 7.4 under 37℃. In addition, pharmacoki- netics of temsirolimus in rats receiving commercial product Torisel and temsirolimus-loaded liposomes was eval- uated after HPLC determination of temsirolimus in rat plasma, cmax and AUC of the liposomes were 2.06- and 1.49-fold improved relative to that of Torisel, respectively. In conclusion, the optimized lyophilized temsirolimus- loaded liposomes with high entrapment efficiency achieved sustained release and significantly increased bioavail- ability of temsirolimus in rats.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2013年第3期234-238,共5页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81072589)~~
关键词
坦西莫司
脂质体
薄膜分散法
冻干
药代动力学
temsirolimus
liposome
film dispersion method
freeze-drying
pharmacokinetics
