Stability of infliximab solutions in different temperature and dilution conditions

Autor: Yoann Le Basle, Valérie Sautou, Philip Chennell, Nicolas Tokhadzé
Přispěvatelé: Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand
Rok vydání: 2018
Předmět:
MESH: Antirheumatic Agents
Time Factors
Clinical Biochemistry
Ion chromatography
MESH: Infliximab
Pharmaceutical Science
MESH: Peptide Mapping
030226 pharmacology & pharmacy
Analytical Chemistry
MESH: Osmolar Concentration
0302 clinical medicine
Drug Stability
MESH: Spectrophotometry
Ultraviolet
Spectroscopy
Fourier Transform Infrared
Drug Discovery
MESH: Nephelometry and Turbidimetry
Spectroscopy
MESH: Technology
Pharmaceutical
Protein Stability
Chemistry
Temperature
MESH: Chromatography
Gel
Chromatography
Ion Exchange
MESH: Temperature
3. Good health
Dilution
Pharmaceutical Solutions
Antirheumatic Agents
030220 oncology & carcinogenesis
Chromatography
Gel
Stability
MESH: Pharmaceutical Solutions
medicine.drug
Monoclonal antibody
MESH: Biosimilar Pharmaceuticals
medicine.drug_class
Drug Compounding
Size-exclusion chromatography
Peptide Mapping
Stability (probability)
MESH: Spectroscopy
Fourier Transform Infrared
Protein Aggregates
03 medical and health sciences
Dynamic light scattering
Nephelometry and Turbidimetry
MESH: Drug Stability
MESH: Protein Stability
medicine
Technology
Pharmaceutical
Biosimilar Pharmaceuticals
Chromatography
Osmolar Concentration
MESH: Time Factors
Analytical
MESH: Chromatography
Ion Exchange
Infliximab
MESH: Protein Aggregates
Chemical instability
MESH: Drug Compounding
Nanoparticles
Chemistry techniques
Spectrophotometry
Ultraviolet
MESH: Nanoparticles
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Journal of Pharmaceutical and Biomedical Analysis
Journal of Pharmaceutical and Biomedical Analysis, Elsevier, 2018, 150, pp.386-395. ⟨10.1016/j.jpba.2017.12.012⟩
Journal of Pharmaceutical and Biomedical Analysis, 2018, 150, pp.386-395. ⟨10.1016/j.jpba.2017.12.012⟩
ISSN: 0731-7085
Popis: International audience; 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.
Databáze: OpenAIRE
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