Abstract
Background: Buccal administration offers direct access to systemic circulation, improving drug bioavailability when compared with the conventional oral route. This advantage depends on the formulation's ability to remain in contact with the buccal mucosa. Attributes such as adhesion and viscosity are suggested to be correlated and contribute to enhanced residence time at the administration site. Methods: Buccal formulations with varying hydroxypropyl cellulose concentrations were prepared. Adhesion, viscosity, and residence time were assessed using a novel combined qualitative and quantitative approach. Drug permeation was evaluated in vitro using a biomimetic membrane and ex vivo using porcine buccal tissue, and it was further enhanced by adding the permeation enhancer benzalkonium chloride. Permeability measurements were integrated with residence time to estimate effective drug delivery. Results: Increasing HPC concentration improved both adhesion and viscosity, with 2% HPCs (F2) showing the strongest effect (45.5 ± 13.7 g), correlating with longer residence time (43.4% drug retained at 2 min vs. ~20% for 0-1% HPC). Although the polymer slightly reduced apparent permeability, when residence time was considered, drug flux increased 1.6-fold compared to the polymer-free formulation (F0), rising from 12.9 × 10(-5) cm/min (F0) to 19.4 × 10(-5) cm/min (F2) after 2 min. The addition of BKC further enhanced permeation, with apparent permeability increasing 1.5-fold vs. F2 and 2.5-fold vs. F0. Conclusions: Buccal liquid preparations' efficacy is influenced by residence time and subsequent drug permeation. Residence time benefits from the synergistic effects of adhesion and viscosity, highlighting the importance of experimentally assessing these parameters during the development of oromucosal products.