Physiological and Biopharmaceutical Perspectives on Orally Disintegrating Buccal Tablets: Mechanistic Insights into Rapid Mucosal Absorption, Drug Transport, and Controlled Release Dynamics

Abstract

Orally Disintegrating Buccal Tablets (ODBTs) provide a rapid, noninvasive platform for systemic drug delivery by combining fast tablet disintegration with efficient absorption through the highly vascularized buccal mucosa. This review integrates physiological and biopharmaceutical perspectives to explain the mechanistic factors governing drug dissolution, mucosal permeation, and controlled release dynamics. The structural features of the buccal epithelium, minimal keratinization, rich blood supply, and avoidance of first-pass metabolism are examined in relation to rapid systemic drug uptake. Salivary composition, mucosal hydration, and enzymatic activity are analyzed for their influence on disintegration, dissolution rate, and diffusion kinetics. Mechanistic drug transport pathways—including transcellular, paracellular, and carrier-mediated routes are described along with the role of mucoadhesion in maintaining tablet contact and modulating release. Key formulation strategies for ODBTs, such as superdisintegrants, mucoadhesive polymers, permeation enhancers, and nano-enabled systems, are discussed in relation to physicochemical performance and kinetic models like Higuchi and Korsmeyer–Peppas. Emerging tools such as physiologically based pharmacokinetic (PBPK) modeling, artificial intelligence-assisted formulation optimization, and pH- or ion-responsive polymers are highlighted for their ability to tailor drug delivery to mucosal physiology. Clinical applications demonstrate the relevance of ODBTs in cardiovascular, neurological, endocrine, and pain-management therapies owing to their rapid onset and improved patient compliance. Challenges including variability in mucosal barrier properties, saliva-mediated dilution, enzymatic degradation, and regulatory requirements for biocompatibility are also addressed. Overall, the convergence of mucosal physiology and advanced formulation strategies positions ODBTs as a promising next-generation platform for adaptable and patient-centered drug delivery.