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

Abstract

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-HCI) 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-HC1 rectal gels prepared with xanthan gum and locust bean gum were practical rectal preparations with rapid absorption and reduced side effects.