Modeling and Monte Carlo simulations in oral drug absorption

Drug dissolution, release and uptake are the principal components of oral drug absorption. All these processes take place in the complex milieu of the gastrointestinal tract and they are influenced by physiological (e.g. intestinal pH, transit time) and physicochemical factors (e.g. dose, particle size, solubility, permeability). Due to the enormous complexity issues involved, the models developed for drug dissolution and release attempt to capture their heterogeneous features. Hence, Monte Carlo simulations and population methods have been utilized since both dissolution and release processes are considered as time evolution of a population of drug molecules moving irreversibly from the solid state to the solution. Additionally, mathematical models have been proposed to determine the effect of the physicochemical properties, solubility/dose ratio and permeability on the extent of absorption for regulatory purposes, e.g. biopharmaceutics classification. The regulatory oriented approaches are based on the tube model of the intestinal lumen and apart from the drug's physicochemical properties, take into account the formulation parameters the dose and the particle size.