Dissolution based drug delivery
A dissolution based delivery system can either be an injectable suspension depot of a poorly soluble drug or a drug dispersed in a suitable slow dissolving matrix. After administration of a dissolution based delivery system the drug or matrix starts to dissolve thereby releasing the drug. Subsequently the drug will diffuse via the interstitial fluid through the tissue membranes into the systemic circulation. Because the release rate of the drug is proportional to the surface area of the dissolving delivery system, the release rate will decrease in time.
The drug delivery from a dissolution based delivery system can be simulated in Comsol Multiphysics™ using the transport of diluted species module and the deformed geometry module. The deformed geometry module is used to simulate the dissolving geometry and the transport of diluted species module to is used to simulate the diffusion process of the drug through the tissue membranes into the systemic circulation.
In order to predict how fast the drug dissolves and diffuses from the dissolution based 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.
Injectable suspension depot
Drug delivery from an injectable suspension depot was simulated using arbitrary information such as molecular weight, drug solubility, diffusivity and pharmacokinetic properties. After administration of 1 mL suspension depot containing 200 mg drug , the thickness and length of the depot were respectively 3 mm and 40 mm with a porosity of 60 wt%.
Subsequently, the drug slowly dissolves and diffuses via the interstitial fluid through the tissue membranes into the systemic circulation. This process is depicted in the following figure. As the drug dissolves, the thickness of the depot decreases and as a consequence the infusion rate and plasma levels also decrease.
Because the dimensions of the suspension depot after administration are highly influenced by injection volume, injection speed, rheological behavior of the suspension, the infusion rate and plasma levels may vary significantly. In order to demonstrate this, the simulation was repeated for different thicknesses. The injected dose remained equal. In the following figure the plasma levels are depicted for a depot with a thickness of 1 mm, 2 mm and 3 mm. It is demonstrated that Cmax varies from 80 to 25 ng/mL respectively.