A case study demonstrating the migration of diethyl phthalate from an ancillary component to the drug product

Abstract

Phthalates are chemical compounds employed as plasticizers in the plastic industry and have been reported to migrate into drug products. The extent of their migration into the drug product depends upon various factors including the chemical nature of the migrant and the permeability of its packaging container. Migration of semi-volatile phthalates such as Diethyl phthalate (DEP) into drug products is often related to the primary and secondary packaging but due to its chemical nature, it could also migrate from an ancillary component. Therefore, it is not only important to screen the primary and secondary components, but also the ancillary materials that are used during the handling of drug products. In our study, we discovered an ancillary material (scotch tape) to be the source of DEP found in an ophthalmic drug product using orthogonal mass spectroscopy techniques (GC–MS and LC–MS). It is evident from our data that DEP migrated from the scotch tape into the drug product crossing the physical barriers provided by the primary (LDPE container closure system) and secondary packaging (carton and label). The tape was used as an ancillary material to wrap the packaged drug product units together for storage in the stability chamber. The primary and the secondary packaging of the drug product did not exhibit any traces of DEP. The aim of this report is to demonstrate how a chemical compound can migrate into the drug product from an ancillary source (which is not a part of its packaging) and adulterate a drug product. The impact of ancillary materials on drug products should be evaluated appropriately prior to their implementation.