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目的:制备CsA固体自微乳,研究自制环孢素A固体自微乳在大鼠体内的药动学参数和相对生物利用度。方法:运用球晶技术制备乙基纤维素多孔微球,联合二氧化硅对CsA自微乳固化,并在2组SD雄性大鼠分别单剂量给予Neoral?和CsA-SSEDDS,按设计采集24h内动态血液样本,采用HPLC法测定血药浓度。应用DAS药动学软件对数据进行拟合,计算药动学参数。结果:自制的CsA固体自微乳载药量较高,粉体学性质较好,单次给药后Neoral?和CsA-SSEDDS的主要药动学参数Cmax分别为(3.03±0.12)μg·mL-1和(3.27±0.18)μg·mL-1,tmax分别为(0.52±0.04)h和(0.51±0.04)h,AUC0→24分别为(13.7±0.6)μg.h·mL-1和(13.33±0.26)μg.h·mL-1。统计学分析结果显示,各主要药动学参数均无显著性差异。以Neoral?为参比制剂,单剂量给药时CsA-SSEDDS的相对生物利用度为97.14%。结论:球晶技术可以用于CsA自微乳的固化,所得CsA固体自微乳在大鼠体内显示与市售新山地明相近的生物利用度。
OBJECTIVE: To prepare CsA solid self-microemulsions and study the pharmacokinetic parameters and relative bioavailability of self-made cyclosporin A solid microemulsion in rats. METHODS: Ethylcellulose porous microspheres were prepared by spherulite technique. Silica was used to solidify CsA self-microemulsions. Neuro? And CsA-SSEDDS were given to two male Sprague-Dawley rats in a single dose for 24 h Dynamic blood samples were determined by HPLC method. Application DAS pharmacokinetic software to fit the data to calculate pharmacokinetic parameters. Results: The self-made CsA solid self-microemulsions had higher drug loading capacity and better powder quality. The main pharmacokinetic parameters Cmax of Neoral? And CsA-SSEDDS were (3.03 ± 0.12) μg · mL (0.52 ± 0.04) h and (0.51 ± 0.04) h for AUC0 → 24 and (13.7 ± 0.6) μg.h · mL-1 and (3.27 ± 0.18) μg · mL- 13.33 ± 0.26) μg.h · mL-1. Statistical analysis showed no significant difference in the main pharmacokinetic parameters. With Neoral? As reference preparation, the relative bioavailability of CsA-SSEDDS in single-dose administration was 97.14%. CONCLUSION: Spherulite technology can be used for the curing of CsA self-microemulsions. The obtained CsA solid self-microemulsions showed similar bioavailability in vivo to the commercially available nerolidol.