Stability of infliximab solutions in different temperature and dilution conditions - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Pharmaceutical and Biomedical Analysis Année : 2018

Stability of infliximab solutions in different temperature and dilution conditions

Résumé

Infliximab is a monoclonal antibody widely used for the treatment of inflammatory diseases. Over the past few years, many studies have assessed that monoclonal antibodies are prone to aggregation under stress conditions. The aim of this study was to investigate the stability of solutions of an infliximab biosimilar (Inflectra®) at different concentrations (0.4, 2 and 10 mg/mL). These solutions were separately submitted to three temperature conditions that are likely to happen during the drug dispensing system: −20 °C, 5 °C and 25 °C. To perform a complete characterization of infliximab physicochemical and structural stability, a wide range of analytical techniques was employed including: visual inspection, subvisible particles counting (HIAC), dynamic light scattering (DLS), size exclusion chromatography (SEC), cation exchange chromatography (CEX), and analysis of primary, secondary and tertiary structure. When stored at 25 °C, chemical instability was the main limiting factor (highlighted by CEX), while SEC showed only some acceptable variations. After a single freeze-thawing cycle, the amount of subvisible particles was significantly increased. Some variations were also visible in CEX and the hydrodynamic diameter was increased after thawing 10 mg/mL samples. In regard of these results, infliximab (Inflectra®) solutions should not be used after a single freeze-thawing cycle between reconstitution and administration to the patient. The results showed stability at 5 °C of up to 14 days for 10 mg/mL solutions and 90 days for 0.4 and 2 mg/mL solutions, whilst samples stored at 25 °C were stable only 7 days at 10 mg/mL and 30 days when diluted.
Fichier principal
Vignette du fichier
2018 - Infliximab - Post print.pdf (1.96 Mo) Télécharger le fichier
2018 - Infliximab - Supplementary data.pdf (785.11 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01705093 , version 1 (29-11-2019)

Identifiants

Citer

Nicolas Tokhadze, Philip Chennell, Yoann Le Basle, Valérie Sautou. Stability of infliximab solutions in different temperature and dilution conditions. Journal of Pharmaceutical and Biomedical Analysis, 2018, 150, pp.386 - 395. ⟨10.1016/j.jpba.2017.12.012⟩. ⟨hal-01705093⟩
448 Consultations
604 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More