辛伐他汀自乳化释药系统处方优化及Beagle犬体内药代动力学  

Formula optimization of simvastatin self-emulsifying drug delivery system and its pharmacokinetics in Beagle dogs

作　　者：冯志英[1] 胡容峰[2] 孙玉亮[2] 赵丽华[2] 苏丹[2] 

机构地区：[1]江苏吴中医药集团有限公司,苏州215128 [2]安徽中医学院安徽省现代中药重点实验室,合肥230038

出　　处：《中国药科大学学报》2009年第2期131-134,共4页Journal of China Pharmaceutical University

摘　　要：目的:优化辛伐他汀自乳化释药系统(SEDDS)处方并对其体外释放及Beagle犬上药代动力学进行研究。方法:以辛伐他汀在不同种类及比例的油相、表面活性剂中的溶解度为考察指标,筛选辛伐他汀SEDDS处方;采用反向透析法测定体外释药性能;采用LC-MS/MS法测定6只Beagle犬经口给予辛伐他汀SEDDS和市售参比制剂后不同时间血药浓度。结果:优化的辛伐他汀SEDDS处方为辛伐他汀20mg、肉豆寇酸异丙酯(IPM)240mg、聚氧乙烯氢化蓖麻油(Cremophor RH-40)160mg、十二烷基硫酸钠0.5%。受试制剂与参比制剂的主要药代动力学参数tmax分别为(4.10±1.70)h和(2.7±0.8)h,cmax分别为(24.14±15.90)ng/mL和(27.85±12.94)ng/mL,t1/2分别为(6.27±3.03)h和(2.83±0.37)h,AUC0-τ分别为(214.05±127.72)ng·h/mL和(142.77±66.54)ng·h/mL,相对生物利用度为(141.60±24.80)%。结论:按优化处方制得的辛伐他汀SEDDS大大提高了辛伐他汀的生物利用度。Aim： To optimize the formula of simvastatin self-emulsifying drug delivery system （SEDDS） and the release kinetics. Methods： In this research, screening the formula of simvastatin SEDDS on the basis of the solu- bility of simvastatin in various kinds and ratios of surfactants and oil phases. Reverse dialysis bag technique was developed for assay of simvastatin SEDDS. Results： The optimized formula of simvastatin SEDDS was composed of simvastatin 20 rag, IPM 240 rag, Cremophor RH-40 160 mg, 0. 5.% of SLS. The pharmacokinetic parameters of the test and reference drugs were as follow： tmax（4. 10± 1. 70） and （2. 7 ±0. 8） h, Cmax（24. 14 ± 15. 90） ng/mL and （27.85 ± 12.94） ng/mL, t1/2（6.27±3.03） h and （2.83±0,37） h and AUCo-T（214.05 ± 127.72） h. ng/mL and （ 142.77 ± 66.54） h· ng/mL, respectively. The relative＇ bioaviliability of the test product to the reference was （ 141.60 ± 24.80） %. Conclusion： The self-emulsifying drug delivery system of simvastatin were prepared successfully. The dosage form significantly increased the bioavailability.

关 键 词：辛伐他汀 自乳化释药系统 生物利用度 药代动力学 

分 类 号：R944[医药卫生—药剂学]