HUMAN BUCCAL ABSORPTION OF CODEINE PHOSPHATE FROM A BIOADHESIVE DRUG-DELIVERY DEVICE

Two mucoadhesive patches (acidic and neutral) for the delivery of code ine phosphate into the cheek mucosa were tested in human volunteers ve rsus a commercially available oral tablet containing the same dose. Ab sorption of the drug was studied with urinary excretion kinetics. The duration of adhesion was 100 to 120 min. The rate and extent of drug a bsorption decreased in the order : peroral tablet much greater than ne ural patch > acidic patch. While drug uptake by the buccal mucosa incr eased with the pH of the patches, the percentage of codeine and metabo lites excreted (relative to the amount which effectively penetrated th e mucosa) was essentially independent of pH. The shift in elimination kinetics following buccal administration suggested that the residence time of the drug in the mucosa was significant. The buccal absorption of codeine from acidic patches, in which the drug is almost fully ioni zed, would appear to require an aqueous permeation pathway through the permeability barrier. It seems that the mucoadhesive component of the patches causes an increase in the transmucosal water flux, which in t urn affects mucoadhesivity and the enhancement of hydrophilic drug abs orption.