Functionally-graded drug delivery systems with binding reactions: Analytical and stochastic approaches for the fraction of drug released

Mathematical modelling and computer simulation are increasingly being used alongside experiments to help optimise and guide the design of drug delivery systems. Recent drug delivery research has (i) highlighted the advantages of drug delivery systems constructed using functionally-graded materials to achieve target release rates and desired dosage levels over time; and (ii) revealed how it is possible for drug to bind to the carrier material and become irreversibly immobilised within the system, reducing the amount of drug delivered. In this paper, we consider the effect of functionally-graded materials and binding reactions on drug release from common slab, cylinder and sphere devices. In particular, two key contributions are presented. First, we outline a deterministic-continuum approach that develops exact analytical expressions for calculating the total fraction of drug released from the device based on a partial differential equation model of the release process. Second, we develop a stochastic-discrete approach for calculating the fraction of drug released over time based on a random-walk model that captures the randomness of the release process and resulting variability in the total fraction of drug released. Both approaches are numerically validated and provide tools for exploring how the fraction of drug released depends on system parameters (e.g. diffusivity and reaction-rate functions induced by the functionally-graded material and binding reactions), insight which may be useful for designers of drug delivery systems. • Functionally-graded drug delivery systems with binding reactions. • Analytical and stochastic approaches for the fraction of drug released. • Analytical approach develops exact expressions based on PDE model. • Stochastic approach uses random-walk model of individual drug particles. • Code implementing and verifying both approaches provided.