Application of Propranolol to the Keratinized Oral Mucosa: Avoidance of First-Pass Elimination and the Use of l-Dodecylazacycloheptan-2-one (Azone) as an Absorption Enhancer of Bioadhesive Film-Dosage Form

The bioavailability of propranolol applied to the oral mucosa was examined in the hamster. The capacity of hamster cheek pouch, used as a model of keratinized oral mucosa, to metabolize propranolol in vitrois enormously lower than that of the liver. Significant amounts of propranolol absorbed from the small intestine were metabolized to naphthoxylactic acid and 4-hydroxypropranolol (4HP) during the passage through the intestinal wall, and then the greater portion of unchanged propranolol and almost all 4HP were subsequently metabolized by hepatic first-pass elimination in vivoThe systemic bioavailabilities of propranolol after the Lntra-small-intestinal loop and the intra-cheek-pouch administrations were 8.4% and 88.5%, respectively. The bioavailability of propranolol was improved further (to 97.1%) by a 1-h pretreatment of the cheek pouch with 5% l-dodecylazacycloheptan-2-one (Azone)-emulsion. Bioadhesive film-dosage forms of propranolol were prepared with hydroxypropyl-cellulose. Both the in vitropermeation and the in vivoabsorption of propranolol across the cheek pouch were enhanced by the incorporation of Azone to the film-dosage form.