Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro to evaluate the effect of the contained preservatives on drug permeation across rabbit nasalmucosa. 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.
In vitro permeation of desmopressin across rabbit nasal mucosa from liquid nasal sprays: The enhancing effect of potassium sorbate
BORTOLOTTI, Fabrizio;COLOMBO, Gaia
2009
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 nasalmucosa. 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
