Coarse-Grained Modeling of Drug Absorption into Plasticized PVC.

Drug losses during infusions can be caused by complex adsorption and absorption phenomena at the interface between aqueous formulations and polymer-based medical devices, most commonly made of plasticized poly(vinyl chloride) (PVC). Despite their success in describing adsorption phenomena, molecular simulation methods are inherently limited by their length and time scales, which precludes their application to the study of absorption processes. Here, we extended this molecular understanding using the Martini 3 coarse-grained framework to explore absorption within plasticized PVC matrices containing either DEHT or TOTM plasticizers. We used a top-down approach to refine intermolecular interactions. After optimizing the solute-water and solute-PVC nonbonded interactions to reproduce experimental partitioning data, we combined potential of mean force (PMF), free-energy perturbation (BAR), and long equilibrium simulations to map both the thermodynamic and kinetic aspects of sorption. This work establishes a transferable coarse-grained framework for modeling drug-polymer interactions over extended time scales, bridging atomistic insights with experimental observations and paving the way toward full infusion-system simulations including excipients and complex polymer formulations.