Rectal absorption and mucosal irritation of rectal gels containing buprenorphine hydrochloride prepared with water-soluble dietary fibers, xanthan gum and locust bean gum

Rectal gels prepared with water-soluble dietary fibers, xanthan gum and locust bean gum, were evaluated as a vehicle for the rectal administration of buprenorphine hydrochloride (BN-HCl) in rabbits. The maximum plasma concentration of buprenorphine (BN) gradually decreased with increase in the gum concentration. The values of the mean residence time (MRT(0-2)) increased in proportion to increasing gum concentration. The absorption of BN from rectal gels containing 0.5, 1 and 2% (w/v) gum compared with those based upon polyethylene glycol (PEG), was more rapid. In particular, the absorption of BN from rectal gels containing 1% (w/v) gum was extremely fast without decreasing the areas under the plasma concentration vs. time curves (AUC(0-2)). The bioavailabilities obtained in rabbits correlated well with the in vitro release rates determined using dialysis tubing. A histopathological study revealed severe mucosal hyperemia, which was thought to be the main characteristic of rectal irritation induced by PEG-base suppositories. These results suggested that BN-HCl rectal gels prepared with xanthan gum and locust bean gum were practical rectal preparations with rapid absorption and reduced side effects.