Mathematical Modeling of the Extractables Release from Multi-Layered Plastic Films used in Drug Product Containers

Abstract

The release of extractables from multi-layered plastic films such as those used in containers for liquid drug products has been investigated. Targeted extractables were chosen from the film’s extractable profile, as elucidated by a controlled extraction study. The total available pool of targeted extractables was ascertained via exhaustive sequential extraction of the film and the film layer responsible for the target extractables was established. This information, along with the film’s structure, was used to produce a mathematical migration model for each of these targets. The film was fashioned into pouches, filled with a simulating solvent and the release of the targeted extractables to the pouches contents was measured. The measured and modeled concentrations were found to be very similar, establishing the model’s ability to effectively mimic the experimental system. This result suggests that mathematical modeling, which is widely used in the food industry to assess the safety of food packaging, may be applicable to packaged pharmaceutical products.