A three-dimensional model has been developed to describe the multiphase release of macromolecular drugs encapsulated in a hydrogel. The heterogeneity of network mesh size was considered by assigning varying diffusion coefficients to the network lattices randomly. Using a stochastic approach, the random nature of diffusion of drug molecules was captured within the network. The simplest form of distribution containing two diffusion coefficients was tested. To generate the drug release profiles for experimental validation under the limitation of computational cost, a simple scaling relationship was employed. Unlike the single-diffusivity model, the dual-diffusivity model showed good agreement with the experimental data in describing the release profiles of macromolecular drugs of three different sizes from chemically cross-linked dextran hydrogels.
Keywords: controlled release; hydrogel; hydrogel network inhomogeneity; mathematical modeling; stochastic simulation.