INVESTIGATION OF RECTAL ABSORPTION OF INDOMETHACIN FROM SUSTAINED-RELEASE HYDROGEL SUPPOSITORIES PREPARED WITH WATER-SOLUBLE DIETARY-FIBERS, XANTHAN GUM AND LOCUST BEAN GUM

Sustained-release hydrogel suppositories prepared with water-soluble dietary fibers, xanthan gum and locust bean gum, were evaluated as a vehicle for rectal administration of indomethacin (IMC) in rabbits. The drug plasma levels were compared with those after rectal administration of commercial suppositories. When the commercial suppositories were given to rabbits, the plasma concentration reached the maximum level at 30 min after administration followed by a quick reduction, while no sharp peak of plasma levels was seen with the hydrogel suppositories. In particular, the plasma levels observed with the hydrogel suppositories of 1% (w/v) gum concentration were sustained much longer than those after dosing with the commercial suppositories; the mean residence times had higher values without a decrease in the area under the plasma concentration vs. time curves. Histopathological study showed good biological safety of the hydrogel suppositories to the rectal mucosa. These results suggested that the IMC hydrogel suppositories prepared with xanthan gum and locust bean gum were a practical rectal preparation with prolonged action and reduced side effects.