The Effects of Permeabilizers on the In Vitro Penetration of Propranolol Through Porcine Buccal Epithelium

Abstract

The purpose of the present study is to test the possibility that oleic acid might increase the permeability of buccal mucosa and thereby facilitate transmucosal drug delivery. Propranolol, a commonly used beta-blocking agent, was chosen as the model drug, and propylene glycol was chosen as a vehicle in which both propranolol and oleic acid are soluble. The flux of propranolol through porcine tissue mounted in perfusion chambers is monitored by ultraviolet spectroscopy. It is found that oleic acid in propylene glycol increases both the initial flux and the flux at steady state. With oleic acid concentrations in the range of 1 through 10%, there was a 3- to 4-fold increase in permeability to propranolol as judged by changes in permeability constant (KP) values. Oleic acid and propranolol also led to a virtual elimination of the lag time and a maximum drug flux exceeding that at steady state within 2 hours. Similar results were obtained with methyl oleate. Oleic acid has a cis double bond between carbons 9 and 10 in an 18-carbon chain, and it is thought that this double bond fluidizes membranes in the outer portion of the epithelium. This effect on membrane fluidity can account for the increase in KP. The effect of oleic acid in propylene glycol on the initial drug flux is mechanistically more complex and is though to be related to changing thermodynamic activity of the drug as water is displaced by propylene glycol in the tissue. Taken together, the present results indicate that permeability enhancement for the purpose of drug delivery through oral mucosa is feasible.