Physics-Based Models of Extraction Kinetics in Solvent-Swollen Polymers: Using Non-Exhaustive Extractions to Estimate Total Extractable Quantities.

Leachables from polymeric medical devices can migrate into the body, potentially impacting patient health. Physics-based mass-transport models can estimate patient exposure but require knowledge of the initial leachable amount, M 0 $$ {M}_0 $$ . Although M 0 $$ {M}_0 $$ can be determined through exhaustive extraction testing, this may be impractical for some solutes due to kinetic or thermodynamic limitations. We developed a free-volume model to estimate M 0 $$ {M}_0 $$ from non-exhaustive extractions, accounting for solvent-swelling effects on solute diffusivity, D $$ D $$ , in polymers. Based on an analysis of polymer/solvent partition coefficients, we also propose a limiting value for the partition coefficient K $$ K $$ . We couple this model to a mass-transport equation to predict M 0 $$ {M}_0 $$ . Validation against experimental data demonstrates order-of-magnitude accuracy for both D $$ D $$ and M 0 $$ {M}_0 $$ . The model is applicable only to rubbery polymers and systems involving relatively hydrophobic polymers, solvents, and solutes. Using the predicted M 0 $$ {M}_0 $$ with a transport model for in vivo exposure yields results similar to those obtained when M 0 $$ {M}_0 $$ is known a priori. Our work shows that non-exhaustive extractions can be used to infer total extractable quantities and conservatively estimate patient exposure.