BIOPHYSICAL KINETIC MODELING OF BUCCAL ABSORPTION

The biophysical model approach is utilized to critically review the state of kinetic models descriptive of the pathways and events that drug molecules encounter as they diffuse across the stratified layers of cells comprising the buccal epithelial tissue. In general, passage through the non-keratinized epithelium occurs by an initial partitioning step and diffusion across the mucosal membrane, transcellular diffusion and concurrent metabolism in parallel with molecular restricted diffusion within a negative field of force across the extracellular space. The review emphasizes: (1) the nature of anatomical and enzymatic barriers; (2) the employment of experimental methods to gainfully provide quantitative mechanistic insights into rate-determining steps and factors; (3) selective case studies and kinetic models which shed light on the interplay of biophysical factors and physicochemical properties of drugs governing transport mechanisms; and (4) gaps in our current mechanistic understanding of the barrier properties of the buccal epithelium. Mathematical descriptions of models are included.