Guan Qingxiang, Zhang Guangyuan, Sun Shilin, Fan Hongbo, Sun Cheng, Zhang Shaoyuan
School of Pharmacy, Jilin University.
Biol Pharm Bull. 2016 May 1;39(5):762-9. doi: 10.1248/bpb.b15-00854. Epub 2016 Mar 3.
To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.
为提高葛根黄酮（PF）的生物利用度，研制了一种由PF、三醋精、肉豆蔻酸异丙酯、聚氧乙烯氢化蓖麻油RH40、1,2 - 丙二醇和聚乙二醇6000（PEG6000）组成的自微乳化药物递送系统（SMEDDS）滴丸。分别考察了其粒径、ζ电位、形态及体外药物释放情况。还在大鼠体内评价并比较了PF - SMEDDS滴丸与市售愈风宁心滴丸的药代动力学和生物利用度。以葛根素作为PF的代表性成分进行分析。动态光散射显示PF - SMEDDS滴丸在水性介质中形成纳米乳液滴大小的能力。介质类型对PF的释放速率无显著影响。PF - SMEDDS滴丸能够提高PF的体外释放速率，且这些滴丸的体外释放明显快于愈风宁心滴丸。PF - SMEDDS滴丸与市售愈风宁心滴丸的t1/2平均值、峰浓度（Cmax）、0至6小时浓度 - 时间曲线下面积（AUC0 - 6h）之间存在显著差异。药代动力学研究表明，PF - SMEDDS滴丸大大提高了PF的生物利用度。灌胃给药后，PF - SMEDDS滴丸的Cmax值和相对生物利用度分别比愈风宁心滴丸平均显著提高了1.69倍和2.36倍。得出结论，PF的生物利用度大大提高，PF - SMEDDS滴丸可能是提高PF口服生物利用度的一种令人鼓舞的策略。
