Abstract:

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.

Key words: 1-deoxynojirimycin, controlled-release pellets, dissolution, bioavailability