Biorelevant dissolution testing of drug-eluting stents: Experiences with a modified flow-through cell setup

Abstract

In vitro dissolution testing of drug-eluting stents (DES) poses a special challenge in terms of apparatus design due to the very specialized local treatment of the vessel wall in the immediate vicinity of the blood flowing through the vessel and the stent lumen. A vessel-simulating flow-through cell was designed to emulate the placement of a DES in vivo and the flow through the lumen in a simplified in vitro setup, which also allows for the examination of distribution processes. The method is based on the compendial flow-through cell apparatus (USP 4), which was modified by the addition of a hydrogel compartment that represents the vessel wall and the adaptation of the flow rate to the blood flow rate in the coronary vessels. A comparison of the dissolution and release results obtained with the vessel-simulating flow-through cell with standard paddle (USP 2) and flow-through cell (USP 4) apparatus methods shows that release from the coating was decelerated by embedding in the hydrogel in the adapted apparatus. Further experiments with both hydrophilic and hydrophobic fluorescent model compounds coated onto the stents were performed to investigate the effects of different method parameters and variations in the coating composition. While release and distribution of hydrophilic fluorescein sodium were dependent on the flow rate and implantation technique, release kinetics of hydrophobic triamterene were influenced by the coating thickness and the model substance content of the coating. These results illustrate the importance of choosing the correct apparatus design and test parameters adapted to biorelevant conditions for specialized dosage forms such as DES.