A dynamic device to simulate intraarticular drug-release kinetics

Pharmacokinetic/pharmacodynamic (PK/PD) modeling of local drug delivery devices is crucial for predicting intraarticular drug concentrations and translating these devices into clinical practice. However, there are limited numbers of PK/PD models for intraarticular drug administrations, and the current in vitro drug testing methods struggle to reflect the in vivo-in vitro correlation. In vitro drug elution kinetics vary based on the testing technique used. Therefore, there is a need for a novel strategy that incorporates the anatomical and physiological characteristics of the joint. In this study, we developed an in vitro testing device, the Dynamic Release Device (DRD), which mimics the joint space. With two different chambers of the DRD, we were able to tune the parameters affecting drug release kinetics, including diffusion, perfusion, and clearance. We demonstrated the effect of fluid flow, flow rate, temperature, and membrane properties on elution kinetics and drug half-life. We also simulated the impact of systemic drug administration on local drug concentration. We compared the pharmacokinetic behavior of a drug delivery device in DRD with a commonly used sample-and-separate system. The results of this study suggest that DRD is a promising in-vitro testing system incorporating key physiological parameters relevant to intraarticular drug transport and clearance. This system has the potential to facilitate preclinical testing of drug delivery devices on the path to clinical trials.