Asian Journal of Microbiology and Biotechnology

Mucoadhesive drug delivery systems have been developed for more than four decades on the premise that prolonging contact between a dosage form and a mucosal surface increases local drug concentration, extends residence time and improves absorption. The premise is intuitively attractive and is supported by a large materials-science literature, yet the clinical output of the field remains modest relative to the volume of preclinical publication. This critical narrative review examines why that discrepancy persists and what would be required to resolve it. Literature retrieved from Europe PMC, Crossref Metadata Search and the Directory of Open Access Journals, supplemented by backward and forward citation tracking, was appraised for methodological adequacy, internal consistency and translational relevance rather than catalogued by dosage form. Four principal conclusions emerge. The classical mechanistic theories of mucoadhesion retain descriptive value but generate few falsifiable predictions, and the shift towards covalent and dynamic-covalent interfacial chemistry has outpaced the conceptual framework used to interpret it. The adhesion substrate is poorly controlled: commercially purified mucins differ from native mucus and from one another in ways that materially alter measured polymer interaction, so a substantial proportion of comparative data reflects substrate selection as much as material performance. The long-standing opposition between mucoadhesive and mucus-penetrating design is better understood as a site-specific optimisation problem governed by mucus turnover than as a general contest between rival philosophies, and available in vivo evidence does not establish the superiority of either strategy across mucosal sites. Measurement remains the central methodological weakness, because detachment force, rheological synergism, particle tracking and interfacial techniques probe different physical phenomena, are seldom reported with parameters sufficient for cross-study comparison, and lack agreed reference materials. The clinical evidence base is correspondingly thin and dominated by small trials of heterogeneous formulations. Research priorities are proposed for benchmark materials, standardised reporting, mechanistically informative characterisation and trial designs capable of isolating the contribution of adhesion from concurrent drug, excipient and vehicle effects.