A general model of coupled drug release and tissue absorption for drug delivery devices

摘要

In this paper we present a general model of drug release from a drug delivery device and the subsequent transport in biological tissue. The model incorporates drug diffusion, dissolution and solubility in the polymer coating, coupled with diffusion, convection and reaction in the biological tissue. Each layer contains bound and free drug phases so that the resulting model is a coupled two-phase two-layer system of partial differential equations. One of the novelties is the generality of the model in each layer. Within the drug coating, our model includes diffusion as well as three different models of dissolution. We show that the model may also be used in cases where dissolution is rapid or not relevant, and additionally when drug release is not limited by its solubility. Within the biological tissue, the model can account for nonlinear saturable reversible binding, with linear reversible binding and linear irreversible binding being recovered as special cases. The generality of our model will allow the simulation of the release from a wide range of drug delivery devices encompassing many different applications. To demonstrate the efficacy of our model we simulate results for the particular application of drug release from arterial stents. (c) 2015 The Authors. Published by Elsevier B.V.