Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability.
aggregates
alternative buffers
biopharmaceuticals
buffer
stability
stress
Journal
Acta pharmaceutica (Zagreb, Croatia)
ISSN: 1846-9558
Titre abrégé: Acta Pharm
Pays: Poland
ID NLM: 9303678
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
accepted:
02
05
2024
medline:
16
9
2024
pubmed:
16
9
2024
entrez:
16
9
2024
Statut:
epublish
Résumé
The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.
Identifiants
pubmed: 39279529
pii: acph-2024-0022
doi: 10.2478/acph-2024-0022
doi:
Substances chimiques
Buffers
0
Antibodies, Monoclonal
0
Excipients
0
Histidine
4QD397987E
Arginine
94ZLA3W45F
Protein Aggregates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
479-493Informations de copyright
© 2024 Blaž Lebar et al., published by Sciendo.
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