Leachables from plastic materials in contact with drugs. State of the art and review of current analytical approaches

Abstract

The plastics used in drug packaging systems and medical devices are composed of homologous polymers and generally contain additives such as antioxidants, plasticizers and others, to improve their physicochemical properties. However, these additives have potential drawbacks due to possible migration or leaching towards the drug product. Leaching can cause a change in the chemical composition of the drug which, in turn, could modify its therapeutic action and, in some cases, its organoleptic properties. Leachables may also be considered a health hazard due to their inherent toxicological properties. The analytical characterization (detection, identification, typification/qualification and quantification) of leachable substances is mandatory and this information must be included in the application dossier for the drug before it can receive regulatory approval. The main aim of this paper is to collect and contextualise the reported analytical approaches for characterising and/or controlling organic leachables from plastic materials in contact with drugs. We also describe the state of the art of leachables in conjunction with a valuable, broad-based compilation of directives and guidelines. We end by presenting an updated collection of leachables both gas and liquid chromatography studies as separation techniques over the last eight years. We decided to focus our review exclusively on organic leachables as there is already a wide body of research on inorganic impurities.

Keywords: Analytical approaches; Drug impurities; Drug products; Leachables and extractables; Risk management.