丹参素缓释微丸的制备及家兔体内药动学研究

Preparation of Danshensu Sustained-release Pellets and Their Pharmacokinetics in Rabbits

目的:制备丹参素24 h缓释微丸并研究其在家兔体内的药动学行为。方法:采用挤出滚圆法制备丹参素含药丸芯,以尤特奇水分散体为缓释包衣材料进行流化床包衣制备缓释微丸,研究制剂在家兔体内药动学行为。结果:所得丹参素缓释微丸圆整度好,包衣均匀,体外达到24 h缓慢释放。家兔口服相同剂量的丹参素速释微丸和缓释微丸后,Cmax分别为(1.45±0.24)μg·mL-1和(0.67±0.13)μg·mL-1,Tmax分别为(2.00±0.30)h和(8.00±0.50)h,MRT分别为(3.50±0.25)h和(10.93±0.26)h。与丹参素速释微丸相比缓释微丸的相对生物利用度为111.28%±1.28%。结论:丹参素缓释微丸可以达到24 h缓释,以AUC为评价指标时,与丹参素速释微丸生物等效。

Objective： To prepare 24 h Danshensu sustained-release pellets, and further evaluate their in vivo pharmaeokineties. Methods： Danshensu sustained-release pellets were prepared by an extrusionspheronization technique and coated with Eduragit aqueous dispersion on a fluidized bed. /n vivo pharmaeokinetics was studied after oral administration of the Danshensu pellets to rabbits. Results： Spherical and uniformly coated pellets were obtained. The cumulated release percent of Danshensu sustained-release pellets in 24 h was more than 90%. The pharmacokinetic parameters for Danshensu immediate-release pellets and sustained-release pellets were respective as follows： peak plasma concentration （Cmax）, 1.45±0.24 μg·mL-1and 0.67±0.13 μg·mL-1; time to peak concentration （Tmax）, 2.00±0.30h and 8.00±0.50 h; mean residence time （MRT）, 3.50±0.25 h and 10.93±0.26 h. Besides, the relative bioavailability of Danshensu sustained-release pellets was 111.28±1.28%. Conclusion： The Danshensu sustained-release pellets were up to the 24 h sustained-release standard and bioequivalent to the immediate-release pellets.