高良姜素介孔二氧化硅纳米粒胃漂浮片制备及比格犬体内口服药动学研究

Preparation and oral pharmacokinetics in beagle dogs study of galangin mesoporous silica nanoparticles gastric floating tablets

关键词:  高良姜素  胃漂浮片  药动学

Key words:  galgenin  gastric floating tablet  pharmacokinetic

摘要:

目的 制备高良姜素介孔二氧化硅纳米粒胃漂浮片(galangin mesoporous silica nanoparticles gastric floating tablets, Gal-MSNs-GFT),评价口服药动学行为及相对生物利用度。方法 制备高良姜素介孔二氧化硅纳米粒(galangin mesoporous silicananoparticles, Gal-MSNs),采用Box-Behnken设计-效应面法优化Gal-MSNs-GFT处方。扫描电镜观察介质中MSNs-GFT形貌,考察Gal-MSNs-GFT在pH0.8～5.0介质中的释药行为。以高良姜素普通片为参考,比较Gal-MSNs-GFT在比格犬体内的口服药动学行为及相对生物利用度。结果 Gal-MSNs-GFT最佳处方为：HPMC K15M、十六醇和NaHCO3用量分别为29.64%、12.13%和15.32%。Gal-MSNs-GFT在pH0.8～5.0介质中可维持缓慢释药行为,12 h累计释放度大于85%,释药行为均符合一级动力学模型。比格犬体内药动学结果显示,Gal-MSNs-GFT达峰时间(tmax)延后至(4.69±0.84)h,血药浓度(Cmax)增加至(583.07±176.65)ng.mL-1,半衰期(t1/2)延长至(5.84±1.98)h,Gal-MSNs-GFT相对生物利用度提高至5.42倍。结论 Gal-MSNs-GFT工艺重复性良好,释药行为平稳,显著提高了高良姜素生物利用度。

Abstract:

OBJECTIVE To prepare galangin mesoporous silica nanoparticles gastric floating tablets (Gal-MSNs-GFT), and to investigated its oral pharmacokinetic behavior and relative bioavailability. METHODS: Galangin mesoporous silica nanoparticles (Gal-MSNs) was prepared firstly, and then Box-Behnken design-response surface method was employed to optimize formulation of Gal-MSNs-GFT. Scanning electron microscope (SEM) was used to observe the morphology of MSNs-GFT in the medium, and the release behavior of Gal-MSNs-GFT in pH 0.8～5.0 medium were also studied. Taking galangin common tablets as reference, oral pharmacokinetic behavior and relative bioavailability of Gal-MSNs-GFT in beagle dogs were investigated. Results: Optimal formulation of Gal-MSNs-GFT: dose of HPMC K15M, Hexadecyl alcohol and NaHCO3 were 29.64%, 12.13% and 15.32%, respectively. Gal-MSNs-GFT could maintain sustained-release behavior in the medium of pH 0.8 to 5.0，cumulative release rate in 12 h was more than 85%, and the drug release behavior conformed to the first-order kinetic model. Pharmacokinetic results in beagle dogs showed that the tmax of Gal-MSNs-GFT was delayed to (4.69±0.84) h, Cmax was enhanced to (583.07±176.65) ng·mL-1, t1/2 was prolonged to (5.84±1.98) h, and the relative bioavailability of Gal-MSNs-GFT was increased to 5.42 times. Conclusion: The repeatability of Gal-MSNs-GFT preparation process was good, release behavior was stable, and the bioavailability of galangin in vivo was significantly improved.