Characterization of Buccal Mucosa as Barrier for Drug Absorption; A Mechanistic Study via Solvent Uptake and Model Drug Permeation Studies

Abstract

Porcine buccal mucosa is abundantly used in drug delivery studies. With the emergence of new buccal barrier models, such as cell culture models, a link between these models and traditional porcine models should be established. The examination of buccal mucosa was divided into two experiments: the uptake of different solvents into the buccal mucosa and an infinite dose permeation study of domperidone from different solvent systems through porcine and EpiOral™ tissue culture models; this aims to find a correlation between the two models. The solvent uptake experiment revealed superb uptake of water by the dried mucosa (>300% increase in weight) and a high uptake of solvents with high solubility parameters (24.8 and 16.6% for propylene glycol (PG) and polyethylene glycol 200 (PEG200), respectively). An unexpected decrease in weight was observed for Transcutol P and Isopropyl myristate (IPM), emphasizing the lipid extraction effect of these solvents. The increase in the weight of dried buccal mucosa by hydrophilic solvents was mainly due to the high level of total phospholipids and the low percentage of lipophilic ceramides. Permeation studies of domperidone (as a model drug) depend on single and binary solvent systems using Franz diffusion cells. Transcutol® P (TC), polyethylene glycol 200 (PEG 200), and polyethylene glycol 400 (PEG 400) were used as the single-solvent systems. Binary solvent systems were prepared using binary mixtures of Transcutol® P and water in three different ratios (20, 40%, and 60%). The flux (J) of domperidone from different solvent systems through both models showed the same system rank: 60% TC > 40% TC> TC > PEG 200> PEG 400> 20% TC. Plotting the values of flux (J) and the permeability coefficient (kp) of domperidone from different systems in the porcine buccal model against the EpiOral™ tissue culture model showed a correlation coefficient (r2) greater than 0.8, which confirms good correlation.Copyright © 20xx by the authors. This article is an open access article distributed under the terms and conditions Creative Commons Attribution-Share Alike 4.0 International Public License (CC BY-SA 4.0)