1-脱氧野尻霉素控释微丸的制备工艺优化及其药动学研究

1-脱氧野尻霉素控释微丸采用挤出滚圆和流化床方法进行制备。首先使用羟丙基甲基纤维素和微晶纤维素等辅料制备分散体、丸芯，再使用羟丙基甲基纳米纤维素邻苯二甲酸酯作为主要包衣材料进行包衣，并装入胶囊。采用SEM观察微丸的微观形态，以及测定其产率、脆碎度、密度、水分含量和粒径分布等物理性质，研究结果显示微丸性质符合中国药典标准规定。在体外释药试验中，溶出介质和放置方式对药物释放无显著影响，释放过程符合Baker-Lonsdale模型。对比研究1-脱氧野尻霉素原料药、分散体微丸和控释微丸在比格犬体内的控释特性，结果表明：与1-脱氧野尻霉素原料药相比，分散体微丸和控释微丸分别使1-脱氧野尻霉素的生物利用度提高了183.37%和243.87%。此外，1-脱氧野尻霉素控释微丸的体内-体外研究的相关性分析可知体外溶出和体内吸收之间呈现良好的线性关系。

Optimization of 1-Deoxynojirimycin Controlled-release PelletsPreparation and Its Pharmacokinetics Study

1-Deoxynojirimycin controlled release pellets were prepared by extrusion-spheronization and fluidized bed. At first, a solid dispersed 1-deoxynojirimycin were made with hydroxypropyl methyl cellulose and microcrystalline cellulose and then it was subsequently coated by hydroxypropyl methylcellulose phthalate to obtain controlled release pellets. The morphology of pellets was observed by scanning electron microscopy and the yield, friability, tapped density, bulk, moisture content, and particle size distribution were also evaluated. The results showed that the properties of pellets conformed to the Chinese pharmacopoeia. In the in vitro drug release test, the dissolution medium(pH value 1.2, 4.0, 5.5, 6.8) and placement method(no placement, 6 months of accelerated placement and 12 months of long-term placement) had no significant effect on drug release, and the release process was consistent with the Baker-Lonsdale model. The controlled release properties of free 1-deoxynojirimycin, dispersible pellets and controlled-release pellets in beagle dogs was compared. The results showed that the dispersible pellets and the controlled release pellets of 1-deoxynojirimycin enhanced bioavailability of 1-deoxynojirimycin by 186.30% and 235.47%, respectively, compared to free 1-deoxynojirimycin. Furthermore, the correlation analysis in vitro-in vivo studies for controlled release matrix pellets of 1-deoxynojirimycin demonstrated good linear relationships between dissolution in vitro and absorption in vivo.