Abstract
Purpose. 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
V. H. L. Lee. Changing needs in drug delivery in the era of peptide and protein drugs. In V. H. L. Lee (ed.), Peptide and Protein Drug Delivery, Marcel Dekker, New York, 1991, pp. 1–56.
Y. W. Chien, Novel Drug Delivery Systems. Marcel Dekker, New York, 1992, pp. 631–745.
V. H. L. Lee, S. Dodda-Kashi, G. M. Grass, and W. Rubas. Oral route of peptide and protein drug delivery. In V. H. L. Lee (ed.), Peptide and Protein Drug Delivery. Marcel Dekker, New York, 1991, pp. 691–738.
D. Harris and J. R. Robinson. Bioadhesive polymers in peptide drug delivery. Biomaterials 11:652–657 (1990).
D. I. Friedman and G. L. Amidon. Oral absorption of peptides: influence of pH and inhibitors on the intestinal hydrolysis of leuenkephalin and analogues. Pharm. Res. 8:93–96 (1991).
Y. W. Chien. Novel Drug Delivery Systems. Marcel Dekker, New York, 1992, pp. 171–177.
J. S. Schwarz, A. Cohen, A. Bar-Ilan, and D. I. Friedman. Design of novel mucoadhesive submicron emulsion for improved drug delivery. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 21:569–570 (1994).
E. H. Rose and L. M. Aledort. Nasal spray desmopressin (DDAVP) for mild hemophilia A and von Willebrand disease. Ann. Intern. Med. 114:563–568 (1991).
I. Gratz, J. Koehler, D. Olsen, M. Afshar, N. DeCastro, P. M. Spagna, S. G. Ablaza, and G. E. Larijani. The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations. J. Thorac. Cardiovasc. Surg. 104:1417–1422 (1992).
M. Cattaneo, P. M. Tenconi, I. Alberca, V. V. Garcia, and P. M. Mannucci. Subcutaneous desmopressin (DDAVP) shortens the prolonged bleeding time in patients with lever cirrhosis. Thromb. Haemost. 64:358–360 (1990).
K. Miller, B. Atkin, and M. L. Moody. Drug therapy for nocturnal enuresis. Current treatment recommendations. Drugs 44:47–56 (1992).
L. H. Shulman, J. L. Miller, and L. I. Rose. Desmopressin for diabetes insipidus, hemostatic disorders and enuresis. Am. Fam. Physician 42:1051–1057 (1990).
J. E. F. Reynolds (ed.). Martindale 29th edition, The Pharmaceutical Press, London, 1989, pp. 1135–1136.
H. Vilhardt and S. Lundin. Biological effect and plasma concentrations of DDAVP after intranasal and peroral administration to humans. Gen. Pharmac. 17:481–483 (1986).
British Pharmacopea, Her Majesty's Stationery Office, London, 1988, Appendix XIV D A173.
H. L. Luesen, C.-M. Lehr, C.-O. Rentel, A. B. J. Noach, A. G. de Boer, J. C. Verhoef, and H. E. Junginger. Bioadhesive polymers for the peroral delivery of peptide drugs. J. Controlled Release. 29:329–338 (1994).
K. Morimoto, T. Iwamoto, and K. Morisaka. Possible mechanisms for the enhancement of rectal absorption of hydrophilic drugs and polypeptides by aqueous polyacrylic acid gel. J. Pharmacobio-Dyn. 10:85–91 (1987).
J. D. Smart, I. W. Kellaway, and H. E. C. Worthington. An in vitro investigation of mucosa-adhesive materials for use in controlled drug delivery. J. Pharm. Pharmacol. 36:295–299 (1984).
J. L. Chen and G. N. Cyr. Compostitions producing adhesion through hydration. In R. S. Manly (ed.), Adhesion in Biological systems, Academic Press, New York, 1970, pp. 161–181.
N. Garty, M. Lusky, M. Zalish, R. Rachmiel, A. Greenbaum, H. Desatnik, R. Neumann, J. F. Howes, and S. Melamed. Pilocarpine in submicron emulsion formulation for treatment of ocular hypertention: a phase II clinical trial. Invest. Ophthalmol. Vis. Sci. 35:2175 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ilan, E., Amselem, S., Weisspapir, M. et al. Improved Oral Delivery of Desmopressin via a Novel Vehicle: Mucoadhesive Submicron Emulsion. Pharm Res 13, 1083–1087 (1996). https://doi.org/10.1023/A:1016023111248
Issue Date:
DOI: https://doi.org/10.1023/A:1016023111248