Ex vivo evaluation of bioadhesive films for buccal delivery of fentanyl.
The goals of this work were (i) to develop bioadhesive films for the buccal delivery of fentanyl, and (ii) to evaluate their performance in vitro using the pig esophageal model. Films were made with polyvinylpyrrolidone (PVP) of two different molecular weights: PVP K30 and PVP K90. Delivery of fentanyl was determined across full-thickness mucosa and across heat-separated epithelium (where the permeability barrier was shown to be located). The influence of film pH was investigated, and it was found that fentanyl permeation increased with increasing pH (i.e., when a higher percentage of the unionized fraction of drug was present). However, at the pH values studied, fentanyl was predominantly ionized suggesting that transport pathways offering a hydrophilic, or polar, environment across the mucosa were available. The transport rates achieved from the PVP films providing the highest delivery suggest that a buccal system of only 1-2 cm(2) in surface area could achieve a therapeutic effect equivalent to a 10 cm(2) transdermal patch, with a much shorter lag-time.
Diaz del Consuelo
Isabel
I
School of Pharmaceutical Sciences, University of Geneva, Quai Ernest-Ansermet 30, Geneva 4, Switzerland.
Falson
Françoise
F
Guy
Richard H
RH
Jacques
Yves
Y
D000268:Adhesiveness; D000278:Administration, Buccal; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers; D004339:Drug Compounding; D004947:Esophagus / Q000378:metabolism; D005283:Fentanyl / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008970:Molecular Weight; D009092:Mucous Membrane / Q000378:metabolism; D010539:Permeability; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013552:Swine
D000701:Analgesics, Opioid; D004337:Drug Carriers; D011205:Povidone; D005283:Fentanyl