Early-stage pharmaceutical development of bilayer buccal films with a chitosan backing layer for local pain management in oral mucositis

Oral mucositis is a painful inflammation and ulceration of the oral mucosa that frequently occurs as a side effect of radiation and chemotherapy that impairs patients' quality of life, making eating and drinking challenging. Local anesthetics applied directly to lesions can provide temporary pain relief without substantial systemic exposure. Buccal films are a promising delivery platform because they protect the sore area while releasing anesthetics locally to the inflamed mucosa. In this work, the mucoadhesive and swelling properties of chitosan were exploited as a backing layer in bilayer films whose inner drug-loaded layer comprised hydroxypropyl methyl cellulose (HPMC). Formulations containing HPMC of two molecular weights (low and high Mw) at concentrations chosen to give similar viscosity in solution (9% and 2.8% w/w, respectively), were tested with chitosan at 2% and 3% w/w. Interactions between chitosan and HPMC were confirmed by QCM-D. Tetracaine and bupivacaine served as model drugs. Films containing 5-10 mg drug were transparent and non-crystalline; higher drug loads produced crystallization on drying. Drug release was monitored simultaneously from the drug-containing layer and the chitosan backing layer in a side-by-side setup, and the best formulation was able to limit the drug release through the backing layer by about 70% for one hour. This early-stage study shows that chitosan is a promising backing layer for bilayer films, reducing the amount of drug released into the oral cavity. Additionally, it may improve mouthfeel and mucosal residence time while enhancing therapeutic efficacy and patient comfort.