Physicochemical Stability of Doravirine (Pifeltro^®): Characterization of Main Degradation Products and Assessment of Stability of Tablets Repackaged in Single-Dose Unit Containers

Abstract

Doravarine (DOR) is an antiviral drug with a marketed authorization for the management of occupational blood and body fluid exposure. The currently existing packaging, consisting of multiple unit bottles comprising 30 tablets, is not fully appropriate for daily nominative dispensing at the hospital. This study aims at assessing the impact of the change in packaging on the key attributes of the drug: assay, impurity profile, and dissolution. As the first step, which is not fully depicted in the literature, the main potential impurities that could appear during storage (i.e., degradation products (DPs) of DOR) were characterized using a forced degradation protocol followed by an LC-MS/MS analysis. These results paved the way for in silico toxicological assessment and targeted degradation product profiling. Based on this study, the assessment of the implication of repackaging on the formation of DOR’s degradation products should be a primary focus.

Keywords

• doravirine
• mass spectrometry
• degradation products
• structural elucidation
• stability
• repackaging