Theoretical Model Studies of Drug Absorption and Transport in the Gastrointestinal Tract I

The simultaneous chemical equilibria and mass transfer of basic and acidic drugs through a two-phase compartment model were theoretically investigated. The model consisted of a well-stirred bulk aqueous phase, an aqueous diffusion layer, and a lipid barrier for perfect and imperfect sink cases. The nonsteady and quasi-steady-state changes in the concentration-distance distributions in the lipid phase were studied. The rate of change of the total drug concentration in the bulk aqueous phase was described in the general form of a first-order equation useful for the evaluation of experiments. A limiting steady-state relationship involving the transport rate with the partition coefficient, pH at the aqueous-lipid interface, dissociation constant of the drug, aqueous and lipid diffusion coefficients, and thickness of the diffusion layer was derived. Increasing the agitation rate in the aqueous phase markedly affects the pH profiles for the rate of transport. The pH-partition theory is shown to be a limiting case of the more general approach presented.