Biodegradable implants that combine diffusion with matrix degradation for extended release.
A degradation-based delivery system is a matrix-type system where the drug is released through a combination of diffusion and degradation of the matrix itself. The drug can be dispersed in biodegradable microspheres, or in a biodegradable implant or rod. After administration, the drug initially diffuses out of the matrix, followed by additional release as the matrix degrades. The drug then diffuses via interstitial fluid through tissue membranes into systemic circulation.
This is simulated in Comsol Multiphysics™ using the transport-of-diluted-species module together with the reaction-engineering module, the latter simulating matrix degradation, the former simulating drug diffusion through tissue membranes. Degradation renders the matrix more brittle and porous, changing its permeability over time. Compartments are defined with their own solubility and diffusivity parameters, linked by flux interactions, to predict how fast the matrix degrades and drug diffuses to systemic circulation.
A biodegradable implant (2 mm thick, 20 mm long) was simulated using arbitrary reaction kinetics, molecular weight, drug solubility, diffusivity and pharmacokinetic values, with hydrolysis as the degradation mechanism. After administration, water diffuses into the implant, initiating matrix degradation, transforming the matrix into its degradation products from the surface inward. Total degradation time for the implant was approximately 3 months.
The infusion rate shows complex behavior: after an initial high (burst) release, the infusion rate rises again after roughly 5 days, as degradation renders the matrix more brittle and porous, enhancing its diffusivity.
