A mechanistic approach for modeling oral drug delivery
A drug release mechanism is combined with a Compartmental Absorption and Transit (CAT) model within a pharmacokinetic framework for predicting orally administered drug release and transport. The developed model is used to evaluate pharmacokinetic metrics such as peak plasma concentration, area under the curve (AUC) and bioavailability. A comparative study has been performed on different cimetidine tablet formulations for which clinical drug profiles are available for model validation. The model predictions are in good agreement with the clinical results. Different scenarios based on induced changes in average patient body weight, fraction of drug in the tablet, tablet radius and their corresponding effects on the model predictions are discussed. The change in average patient body weight has a low effect on the plasma concentration profile while the fraction of drug in the tablet has a strong effect. In a scenario study within an optimization framework, the model has been able to determine the optimal dimensions of a tablet of fixed dosage in order to obtain maximum therapeutic effect from the tablet. (C) 2013 Elsevier Ltd. All rights reserved.
oral drug delivery optimization acat model dissolution model pharmacokinetic model