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

Abstract

High processing temperatures restrict spray drying applications for heat sensitive biologics. This work highlights the potential of Phosphate Buffer Saline (PBS) as the sole stabilising excipient when spray drying large biologics via a complimentary buffer component effect. Fibrinogen (∼340 kDa) was spray dried in PBS at various temperatures and concentrations, followed by assessment of the protein's structural integrity by UV–Vis, ATR-FTIR, SEM, and PXRD analyses. Experimental findings demonstrate that fibrinogen can maintain structural integrity when spray dried at temperatures up to 60 °C (T_out), when PBS is used as the sole stabilising excipient in combination with rapid drying rates. Results show a synergistic effect between the phosphate and salt components of the buffer when subjected to rapid drying rates mitigating protein aggregation and preserving protein secondary and tertiary structures. Stability studies conducted over 90 days indicated that powders stored under low humidity retained structural integrity. Findings provide valuable insights into the feasibility of spray drying large biologics through understanding the individual stabilising effects of PBS buffer components coupled with the rapid drying times. This approach offers a promising and scalable formulation strategy for the pharmaceutical industry in developing an alternative to freeze drying methods, offering advantages in cost, processing time, and product stability.