Stabilising large biologics through complimentary buffer component protection and rapid drying times

Area of Science:

• Biopharmaceutical formulation
• Protein stabilization
• Spray drying technology

Background:

• High processing temperatures limit spray drying for heat-sensitive biologics.
• Developing alternative stabilization methods is crucial for large biomolecules.

Purpose of the Study:

• To investigate Phosphate Buffer Saline (PBS) as a sole excipient for spray drying large biologics.
• To assess the structural integrity of fibrinogen spray-dried using PBS.

Main Methods:

• Spray drying of fibrinogen (∼340 kDa) in PBS at various temperatures and concentrations.
• Analysis of protein structural integrity using UV-Vis, ATR-FTIR, SEM, and PXRD.
• 90-day stability studies under low humidity conditions.

Main Results:

• Fibrinogen maintained structural integrity when spray dried up to 60°C (T_out) using PBS as the sole excipient.
• Synergistic effects of phosphate and salt components in PBS mitigated aggregation and preserved protein structure.
• Spray-dried powders stored under low humidity retained structural integrity over 90 days.

Conclusions:

• PBS acts as an effective sole stabilizing excipient for spray drying large biologics.
• Rapid drying rates combined with PBS buffer components preserve protein structure.
• This spray drying approach offers a scalable, cost-effective alternative to freeze-drying for pharmaceuticals.