Drug absorption is a complex process dependent upon drug properties such as solubility and permeability, formulation factors, and physiological variables including regional permeability differences, pH, luminal and mucosal enzymes, and intestinal motility, among others. Despite this complexity, various qualitative and quantitative approaches have been proposed for the estimation of oral drug absorption. These approaches are reviewed in this article with particular emphasis on drug dissolution modelling, dynamic systems for oral absorption and absorption models based on structure. The regulatory aspects of oral drug absorption and in particular the biopharmaceutic classification of drugs are also discussed. Models for drug dissolution and release describe adequately the in vitro data, and models for oral drug absorption provide reasonable results. The development of in vitro-in vivo correlations based on the official compendia specifications are facilitated using commercial computer packages.

We use Monte Carlo simulations in order to study diffusion controlled drug release from matrices consisting of random mixtures of high and low diffusivity areas (random mixing), and from matrices covered by a thin film of low diffusivity (ordered mixing). We compared our results with the Weibull model for drug release and found that it provides an adequate description of the release process in all cases of random mixing and most cases of ordered mixing. We have studied the dependence of the Weibull parameters on the diffusion coefficient and, in most cases, found a rather simple linear dependence. Moreover, our results indicate that a device covered by a thin film with diffusion coefficient three orders of magnitude lower that the coefficient of the rest of the device, will release drug at constant rate for most of the release process. This last result may have considerable practical applications. (C) 2007 Elsevier B.V. All rights reserved.

Three advanced models of pharmacokinetics are described. In the first class are physiologically based pharmacokinetic models based on in vitro data on transport and metabolism. The information is translated as transporter and enzyme activities and their attendant heterogeneities into liver and intestine models. Second are circulatory models based on transit time distribution and plasma concentration time curves. The third are fractal models for nonhomogeneous systems and non-Fickian processes are presented. The usefulness of these pharmacokinetic models, with examples, is compared.