In vitro permeation of desmopressin across rabbit nasal mucosa from liquid nasal sprays: The enhancing effect of potassium sorbate

Bortolotti, F; Balducci, AG; Sonvico, F; Russo, P; Colombo, G

In vitro permeation of desmopressin across rabbit nasal mucosa from liquid nasal sprays: The enhancing effect of potassium sorbate

Bortolotti, F Balducci, AG Sonvico, F

Russo, P Colombo, G

Permalink

Publication Type:: Journal Article
Citation:: European Journal of Pharmaceutical Sciences, 2009, 37 (1), pp. 36 - 42
Issue Date:: 2009-04-11

Closed Access

	Filename	Description	Size
	2011006092OK.pdf	Published Version	89.63 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Bortolotti, F	en_US
dc.contributor.author	Balducci, AG	en_US
dc.contributor.author	Sonvico, F https://orcid.org/0000-0001-7372-1456	en_US
dc.contributor.author	Russo, P	en_US
dc.contributor.author	Colombo, G	en_US
dc.date.available	2008-12-22	en_US
dc.date.issued	2009-04-11	en_US
dc.identifier.citation	European Journal of Pharmaceutical Sciences, 2009, 37 (1), pp. 36 - 42	en_US
dc.identifier.issn	0928-0987	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32560
dc.description.abstract	Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro to evaluate the effect of the contained preservatives on drug permeation across rabbit nasal mucosa. Experiments were performed using Franz-type diffusion cells with rabbit nasal mucosa as model barrier. Transport profiles obtained in comparison with a preservative-free solution evidenced that in the presence of preservatives DDAVP permeation in vitro always increased (p < 0.05), although at different extents (chlorobutanol < benzalkonium < sorbate). While for benzalkonium structural damage of the mucosa could occur decreasing its barrier properties, the effect of sorbate on drug transport was further investigated, being less studied. After having found that sorbate permeated together with DDAVP, the hypothesis that the two compounds formed an ion pair in solution with improved permeability was made. Additional experiments with aqueous test solutions reconstructed ad hoc containing desmopressin and varying sorbate concentrations confirmed the enhancing effect of sorbate, which however resulted to be independent of sorbate concentration. In conclusion, preservatives significantly enhanced desmopressin permeation in vitro across rabbit nasal mucosa with different mechanisms. If a correlation existed between these data and in vivo DDAVP bioavailability after nasal administration, this could strengthen the safety concerns related to the use of this medication in adults and children. © 2008 Elsevier B.V. All rights reserved.	en_US
dc.relation.ispartof	European Journal of Pharmaceutical Sciences	en_US
dc.relation.isbasedon	10.1016/j.ejps.2008.12.015	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Nasal Mucosa	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rabbits	en_US
dc.subject.mesh	Chlorobutanol	en_US
dc.subject.mesh	Benzalkonium Compounds	en_US
dc.subject.mesh	Sorbic Acid	en_US
dc.subject.mesh	Adjuvants, Pharmaceutic	en_US
dc.subject.mesh	Preservatives, Pharmaceutical	en_US
dc.subject.mesh	Administration, Intranasal	en_US
dc.subject.mesh	Diffusion	en_US
dc.subject.mesh	Therapeutic Equivalency	en_US
dc.subject.mesh	Permeability	en_US
dc.subject.mesh	Deamino Arginine Vasopressin	en_US
dc.subject.mesh	In Vitro Techniques	en_US
dc.title	In vitro permeation of desmopressin across rabbit nasal mucosa from liquid nasal sprays: The enhancing effect of potassium sorbate	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	37	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	37	en_US

Abstract:

Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro to evaluate the effect of the contained preservatives on drug permeation across rabbit nasal mucosa. Experiments were performed using Franz-type diffusion cells with rabbit nasal mucosa as model barrier. Transport profiles obtained in comparison with a preservative-free solution evidenced that in the presence of preservatives DDAVP permeation in vitro always increased (p < 0.05), although at different extents (chlorobutanol < benzalkonium < sorbate). While for benzalkonium structural damage of the mucosa could occur decreasing its barrier properties, the effect of sorbate on drug transport was further investigated, being less studied. After having found that sorbate permeated together with DDAVP, the hypothesis that the two compounds formed an ion pair in solution with improved permeability was made. Additional experiments with aqueous test solutions reconstructed ad hoc containing desmopressin and varying sorbate concentrations confirmed the enhancing effect of sorbate, which however resulted to be independent of sorbate concentration. In conclusion, preservatives significantly enhanced desmopressin permeation in vitro across rabbit nasal mucosa with different mechanisms. If a correlation existed between these data and in vivo DDAVP bioavailability after nasal administration, this could strengthen the safety concerns related to the use of this medication in adults and children. © 2008 Elsevier B.V. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/32560