Mixing-tank model for predicting dissolution rate control or oral absorption.

A mixing-tank model is used to simulate GI absorption of nonionized drugs. The model is useful for predicting circumstances under which dissolution rate dominates membrane transport and transit rate, thus limiting the extent of absorption. The model is developed from mass balance considerations in which the nonsink dissolution term is a function of the remaining surface area and the concentration gradient across the boundary layer. Other dissolution parameters include initial particle radius, dose, diffusivity, density, and boundary-layer thickness. Readily calculable estimators for the general solution of the model are derived and their ranges of usefulness are discussed. Drug examples chosen for simulation are griseofulvin and digoxin. The model correctly predicts bioavailability as a function of particle size for both of these poorly soluble drugs.