Degradation based drug delivery
A degradation based delivery system is a matrix type system where the drug is released by a combination of drug diffusion and degradation of the matrix. The drug can either be dispersed in biodegradable microspheres or dispersed in a biodegradable implant or rod. After administration of the biodegradable delivery system the drug will initially diffuse out of the matrix followed by an additional drug release due to degradation of the matrix. Subsequently the drug will diffuse via the interstitial fluid through the tissue membranes into the systemic circulation.
Drug delivery from a degradation based delivery system can be simulated in Comsol Multiphysics™ using the transport of diluted species module and the reaction engineering module. The reaction engineering module is used to simulate the degradation process of the matrix and the transport of diluted species module to is used to simulate the diffusion process of the drug out of the matrix through the tissue membranes into the systemic circulation. Degradation of the matrix will result in a more brittle and porous matrix that exhibits different permeability properties. In order to predict how fast the matrix degrades and the drug diffuses from the delivery system to the systemic circulation, compartments are defined in Comsol Multiphysics™, each with their specific solubility and diffusivity parameters. Interaction between the compartments is incorporated in the model by defining fluxes between the compartments.
There are several mechanisms through which degradation of the drug delivery system can occur. Most often degradation occurs as a result of hydrolysis, oxidation or enzymatic degradation.
Drug delivery from a biodegradable implant with a thickness and length of respectively 2 mm and 20 mm was simulated using Comsol Multiphysics™ using arbitrary information such as reaction kinetics, molecular weight, drug solubility, diffusivity and pharmacokinetic properties. The mechanism of degradation was hydrolysis. After administration of the implant, water diffuses in the implant thereby initiating the degradation process of the matrix. The following figure depicts the transformation of the matrix into its degradation products. The Y-axis depicts the concentration of matrix and degraded matrix material. The X-axis depicts the radius of the implant where 0 and 1 are respectively the center and surface of the implant. The total degradation time of the implant was approximately 3 months.
After release, the drug diffuses via the interstitial fluid through the tissue membranes into the systemic circulation. This process is depicted in the following figures.
The infusion rate shows a complex behavior. After a high initial release (burst release), the infusion rate increases again after 5 days. This behavior is due to degradation of the matrix. Degradation will result in a more brittle and porous matrix that enhances the diffusivity properties.