COMBINED EFFECTS OF PH, COSOLVENT AND PENETRATION ENHANCERS ON THE INVITRO BUCCAL ABSORPTION OF PROPRANOLOL THROUGH EXCISED HAMSTER-CHEEK POUCH

The combined effect of pH and vehicle composition on the buccal absorption of propranolol has been evaluated in vitro using hamster cheek pouch. Ethanol was used as cosolvent in various binary-water mixtures. Lauric acid, 1-menthol, sodium salicylate and phosphatidylcholine were evaluated as penetration enhancers. Isopropyl myristate was used as a model of the mucosal lipid phase in partitioning experiments. Permeation of propranolol increased in extent with increasing pH of the vehicle, as compared with the unionized lipophilic fraction of the drug. Permeation of propranolol was decreased at pH 9.4 and increased at pH 6.8 on the addition of ethanol. Ethanol increases the solubility of propranolol in the aqueous vehicle and reduces the oil/vehicle partitioning of the drug through a thermodynamic effect. In addition, at low concentration, ethanol is assumed to increase the permeability of the buccal mucosa to the polar ionized form of propranolol, while higher concentration is required to enhance the diffusivity of the nonpolar unionized form. Menthol and lauric acid were effective at promoting the buccal absorption of propranolol only when the drug was ionized. It was assumed that the mechanism of permeation enhancement was an interaction with the membrane components for 1-menthol, increasing the diffusibility of propranolol, whereas lauric acid may form a more partitionable complex with the drug without any action on membrane permeability.