Modeling the Permeation Rates of Organic Migrants through a Fluoropolymer Film

Polymer films have been widely used as barriers for blocking certain organic molecules (such as leachables and extractables) in both food and parenteral pharmaceutical packaging applications. However, a good understanding of the barrier properties of those polymer films is still lacking for combination drug product manufacturers to make practical risk-based assessments regarding the effectiveness of the barrier films against potential leachables. The present work addressed this issue by a combined theoretical/experimental approach-a new mathematical model based on Hansen Solubility Parameters, the size and shape of organic molecules, was developed to quantitatively estimate the Steady-State Permeation Rate of organic migrants through a model ethylene-tetrafluoroethylene fluoropolymer film by considering contributions from both solubility and diffusivity. This model facilitates expedited screening of potential leachables, allowing for experimental focus on higher-risk leachables and ultimately enabling rapid combination drug product development.LAY ABSTRACT: Currently, there is a shortage of simple mathematical models that can accurately estimate the effectiveness of the barrier properties of polymer films; therefore, practical assessment of the barrier properties of these materials is mainly realized by experimental measurements of the permeation rates of interested migrants. These measurements can be time-consuming, costly, and inaccurate. Sometimes these measurements are even impossible if the migrant molecules are not commercially available (although we might know their molecular structures). Thus, there is a need for a practical and easy-to-use mathematical model that can estimate/predict the permeation rate through these barrier materials. To satisfy this need, we developed a new model based on the molecular polarity, size, and shape of migrant molecules to quantitatively estimate the permeation rate of the migrant molecules through these barrier materials. This model will be useful for applications in both food and drug packaging. Additionally, this model will be useful for medical devices or containers that will hold or store organic drug molecules, such as medical tubing or IV bags. Finally, organic compounds used in inks and adhesives that will permeate through packaging materials could also be modeled in the same fashion.