A pullulan-based bilayer film for buccal delivery of a GLP-1 peptide analogue

The buccal route has re-emerged as an alternative non-injectable route for peptide delivery. However, buccal peptide bioavailability is low, necessitating new formulation strategies. Pullulan, a water-soluble carbohydrate polymer, offers potential as a film-forming agent for buccal peptide delivery. Our aim was to co-administer a glucagon-like peptide-1 receptor agonist (GLP-1 RA) model analogue with an epithelial permeation enhancer, sodium glycodeoxycholate (GDC) in a bilayer film using a pullulan-based mucoadhesive layer. A pullulan–carboxymethyl cellulose mucoadhesive layer was selected, along with a backing layer made from an ammonio-methacrylate copolymer (Eudragit® RLPO). Physicochemical characterization confirmed the suitability of the pullulan-based film for buccal application. A Hilltop Chamber comprising an adhesive-backed cotton pad identified an optimal GLP-1 RA:GDC ratio for peptide permeation across ex vivo porcine buccal mucosae. 200 mM GDC (94.4 mg/mL) enabled ∼6% flux at 3 h using a donor concentration of 50 mg/mL GLP-1 RA (∼1:2). When these concentrations were incorporated into the prototype pullulan films, GLP-1 RA fluxes across mucosae reached ∼4.5% and ∼2% at 3 h for single mucoadhesive-layer and bilayer films, respectively, without overt tissue damage. Integrating GLP-1 RA and GDC into a pullulan–based bilayer film offers a promising carbohydrate polymer platform for enhancing buccal peptide delivery.