环孢素A固体自微乳的制备及评价  

Preparation and evaluation of cyclosporin A solid self-emulsion

作　　者：白中稳[1,2] 胡容峰[1,2,3] 孙备[4] 胡晓[1,2] 

机构地区：[1]安徽中医学院药学院,安徽合肥230031 [2]安徽省中药研究与开发重点实验室,安徽合肥230038 [3]安徽省"115"现代中药研发创新团队,安徽合肥230038 [4]安徽省药物研究所,安徽合肥230022

出　　处：《中国医院药学杂志》2013年第7期514-519,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(项目编号:81274100);安徽省学术和技术带头人及后备人选学术科研活动经费资助项目(皖人社秘[2011]381号-26);安徽省高层次人才创新创业资金(项目编号:2009Z061)

摘　　要：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-microemulsion and study the pharmacokinetics and relative bioavailability of cyclosporin A solid self-emulsifying in rats. METHODS The spherical crystallization technique was used prepare porous mi- crospheres of ethyl cellulose; in conjunction with Aerosil treating CsA microemulsion; The cyclosporin A concentration in blood was determined by HPLC. Single dose of CsA-SSEDDS po and that of Neoral po were given in two groups of rats respective ly. The data was processed by the software DAS. The pharmacokinetic parameters were estimated by a statistic analysis of ANOVA. RESULTS Self-restraint CsA solid selgmicroemulsion had higher drug loading and better powder properties. The C t AUC0→24 of Neoral and CsA SSEDDS were （3.03±0.12）μg·mL^-1 and （3.27±0.18）μg·mL^-1 , （0.52±0.04）h and （0.52±0.04）h, （13.7±0.6）μg.h·mL^-1 and （13.33±0.26）μg.h·mL^-1, respectively. The mean relative bioavailahility of the CsA-SSEDDS vs Neoral was 97. 14%. The analyzed results showed that there was no significant difference between two groups. CONCLUSION Spherical crystallization technique can be used for the treating CsA microemulsion, the resuls of which suggested that cyclosporin A solid self-emulsion had the similar bioavailability compared with Neoral.

关 键 词：球晶技术 环孢素A固体自微乳 高效液相色谱法 药动学 生物利用度 

分 类 号：R943[医药卫生—药剂学]