Stability of infliximab solutions in different temperature and dilution conditions.
J Pharm Biomed Anal
; 150: 386-395, 2018 Feb 20.
Article
em En
| MEDLINE
| ID: mdl-29287266
ABSTRACT
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 10â¯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 10â¯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 14â¯days for 10â¯mg/mL solutions and 90â¯days for 0.4 and 2â¯mg/mL solutions, whilst samples stored at 25⯰C were stable only 7â¯days at 10â¯mg/mL and 30â¯days when diluted.
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Base de dados:
MEDLINE
Assunto principal:
Temperatura
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Antirreumáticos
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Medicamentos Biossimilares
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Infliximab
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França