IMPROVED ORAL DELIVERY OF DESMOPRESSIN VIA A NOVEL VEHICLE - MUCOADHESIVE SUBMICRON EMULSION

Purpose. Desmopressin acetate (DDAVP) is used parenterally and intrana sally in the control of several diseases. Oral administration of DDAVP , while most desirable, is not practical presently due to low bioavail ability. The objective of the present study was to explore the feasibi lity for employing oil-in-water MucoAdhesive SubMicron Emulsion (MA-SM E), a novel mucoadhesive vehicle with polymer-coated droplets, for enh anced oral delivery of DDAVP. Methods. We used a modified pharmacopeal method, based on measurement of the antidiuretic activity, for the as sessment of oral delivery of DDAVP in rats. DDAVP formulated in two MA -SME preparations, in non-mucoadhesive SME (plain-SME), in saline and in other control solutions was administered orally to rats via a stoma ch tube at a dose of 0.5 units/kg. At various times following DDAVP ad ministration, water was given via a stomach tube. Excretion times for 30% and 60% of the total water load were measured. Results. Excretion times for DDAVP in MA-SME formulations were always longer (up to 2-fol d) than those following DDAVP in saline. By contrast, excretion times for DDAVP in plain-SME and in non-SME Carbopol (a Mucoadhesive polymer ) solution were virtually identical to those for DDAVP in saline. Conc lusions. Formulations of MA-SME were shown to generate substantial enh ancement (up to 12-fold) of the rat oral bioavailability of DDAVP with regard to simple saline solution of the drug. From the results it is also evident that MA-SME, but not plain-SME or non-SME Carbopol soluti on, is responsible for the enhancement of oral delivery of DDAVP in ra ts.