Controlled-Release Preparation of Indomethacin Using Calcium Alginate Gel

抄録

Alginate gel beads containing indomethacin (IMC) were prepared using a gelation of alginate with calcium cation. Though IMC was not released from the beads at pH 1.2 because of its extremely low solubility in aqueous media, it was released according to the swelling of alginate gel at pH 6.8. The release of IMC from the beads decreased with the decreasing ratio of mannuronic acid (M) to guluronic acid (G) in alginate, and with the larger molecular weight or alginate. The maximum concentration and the area under the time curve of plasma concentration of IMC after oral administration of alginate gel beads to beagle dogs were lower than those of IMC powder. The absorption rate of IMC was lower and more prolonged after administration of beads containing IMC than IMC powder alone. The high plasma concentration of IMC was maintained because absorption continued for a longer period when the bead consisting of the alginate with 0.65 M-block/G-block ratio and 66000 molecular weight was administered. The availability of alginate gel beads of IMC was further demonstrated by oral administration to human volunteers. A serum concentration which was comparable to maximum serum concentration was maintained from 2 to 6 h after administration, while an effective serum concentration was maintained even 12 h after administration of the beads. These data suggest that alginate is useful for a controlled-release formulation of IMC.