Injectable suspension depots that release a poorly soluble drug as they slowly dissolve.
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, the drug or matrix starts to dissolve, releasing the drug, which then diffuses via interstitial fluid through tissue membranes into systemic circulation. Because release rate is proportional to the surface area of the dissolving delivery system, the release rate decreases over time.
This process is simulated in Comsol Multiphysics™ using the transport-of-diluted-species module together with the deformed-geometry module, the latter simulating the dissolving geometry itself, the former simulating diffusion of the drug through tissue membranes into systemic circulation. As with other delivery systems, compartments are defined with their own solubility and diffusivity parameters, linked by flux interactions.
Simulated using arbitrary molecular weight, drug solubility, diffusivity and pharmacokinetic values. After administering 1 mL of suspension depot containing 200 mg of drug, the depot measured 3 mm thick by 40 mm long, with 60 wt% porosity.
As the drug dissolves, depot thickness decreases, and infusion rate and plasma levels decrease along with it.
Because depot dimensions after injection are highly sensitive to injection volume, injection speed and the suspension's rheology, infusion rate and plasma levels can vary significantly. Repeating the simulation at 1 mm, 2 mm and 3 mm depot thickness (same injected dose) showed Cmax varying from 80 ng/mL down to 25 ng/mL, respectively.
