Transport of fentanyl through pig buccal and esophageal epithelia in vitro: influence of concentration and vehicle pH

To validate pig esophageal epithelium as a model for the permeability barrier of the buccal mucosa, the transport of fentanyl across the two tissues was compared in vivo. The epithelia were separated by immersing the excised mucosae into an isotonic saline solution at 60--65 degrees C. Fentanyl was delivered as the citrate salt at a concentration of 1 or 2 mg/mL buffered at one of four pH values (between 6.0 and 7.4). Across both barriers, drug transport increased proportionally with concentration as expected. However, drug flux was not linearly related to the unionized fraction of the drug; indeed, fentanyl delivery was significant even when 98.5% of the drug was in the ionized form. Buccal and esophageal fluxes were very similar under all conditions suggesting that the esophageal epithelium is a representative tool for buccal transport studies in vitro.