Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability

Lebar, Blaž (avtor), Zidar, Mitja (avtor), Mravljak, Janez (avtor), Šink, Roman (avtor), Žula, Aleš (avtor), Pajk, Stane (avtor)

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 analysing soluble aggregate formation through size exclusion chromatography. At low protein concentration, protein instability after temperature stress was exclusively observed in the bis-TRIS/glucuronate buffer. Conversely, freeze-thaw stress led to 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 histidine/HCl buffer further enhanced protein stability during freeze thaw cycles. At high protein concentration, 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.

• Jezik: Angleški jezik
• Ključne besede: biopharmaceuticals, buffer, stress, aggregates, alternative buffers, stability
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 479–493
• Številčenje: Vol. 74, no. 3
• PID: 20.500.12556/RUL-163471
• UDK: 615.4:54
• ISSN pri članku: 1846-9558
• DOI: 10.2478/acph-2024-0022
• COBISS.SI-ID: 197188099
• Datum objave v RUL: 07.10.2024

Gradivo je del revije

• Naslov: Acta pharmaceutica
• Skrajšan naslov: Acta pharm.
• Založnik: Croatian Pharmaceutical Society
• ISSN: 1846-9558
• COBISS.SI-ID: 3817585

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biofarmacevtika, pufer, stres, agregati, alternativni pufri, stabilnost, farmacevtska kemija

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Novartis Pharmaceutical Manufacturing LLC

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin