A comparative ex vivo drug permeation study of beta-blockers through porcine buccal mucosa

Apparent permeability coefficients (k(p)) of a series of beta-blockers: acebutolol, atenolol, labetalol, metoprolol, oxprenolol and propranolol, through porcine buccal mucosa were determined. The aim of the study was to determine the permeation parameters (apparent permeability coefficient, k(p); flux, J; and lag time, T-L) as a measure of the intrinsic permeability of porcine buccal mucosa to these drugs, in order to predict the efficacy of their possible administration through human buccal mucosa. A positive linear correlation was observed between the apparent permeability coefficient, k(p)and the partition coefficient, P. Oxprenolol and propranolol are the drugs that presented the highest values of k(p): 0.3231 x 10(2) cm/h and 0.5666 x 10(2) cm/h, respectively. Multiple linear regression (MLR) using least square estimation was performed on the data set with log k(p)as dependent variable and the descriptors as predictor variables. The potential systemic capacity after a buccal administration was predicted by estimating the plasma concentrations at steady-stated (C-ss). Considering the entire process of permeation ex vivo, propranolol and oxprenolol would seem to be the best candidates for administration through the buccal mucosa. (C) 2014 Published by Elsevier B. V.