Improved oral delivery of desmopressin via a novel vehicle: mucoadhesive submicron emulsion.
OBJECTIVE
Desmopressin acetate (DDAVP) is used parenterally and intranasally in the control of several diseases. Oral administration of DDAVP, while most desirable, is not practical presently due to low bioavailability. The objective of the present study was to explore the feasibility for employing oil-in-water MucoAdhesive SubMicron Emulsion (MA-SME), a novel mucoadhesive vehicle with polymer-coated droplets, for enhanced oral delivery of DDAVP.


METHODS
We used a modified pharmacopeal method, based on measurement of the antidiuretic activity, for the assessment 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 stomach tube at a dose of 0.5 units/kg. At various times following DDAVP administration, 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-fold) 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.


CONCLUSIONS
Formulations of MA-SME were shown to generate substantial enhancement (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 solution, is responsible for the enhancement of oral delivery of DDAVP in rats.
Ilan
E
E
Pharmos Ltd., Kiryat Weizmann, Rehovot, Israel.
Amselem
S
S
Weisspapir
M
M
Schwarz
J
J
Yogev
A
A
Zawoznik
E
E
Friedman
D
D
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004655:Emulsions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004655:Emulsions; D012076:Renal Agents; D003894:Deamino Arginine Vasopressin