Foley Laura, Steiner-Browne Marina, O'Reilly Emmet
SSPC the SFI Research Centre for Pharmaceuticals, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
Int J Pharm X. 2025 Aug 12;10:100374. doi: 10.1016/j.ijpx.2025.100374. eCollection 2025 Dec.
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), 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.
高温处理限制了喷雾干燥在热敏性生物制品中的应用。这项工作突出了磷酸盐缓冲盐水（PBS）作为唯一稳定辅料在通过互补缓冲成分效应喷雾干燥大型生物制品时的潜力。在不同温度和浓度下，将纤维蛋白原（约340 kDa）在PBS中进行喷雾干燥，随后通过紫外可见光谱、衰减全反射傅里叶变换红外光谱、扫描电子显微镜和粉末X射线衍射分析评估蛋白质的结构完整性。实验结果表明，当以PBS作为唯一稳定辅料并结合快速干燥速率时，纤维蛋白原在高达60°C的温度下进行喷雾干燥时能够保持结构完整性。结果显示，在快速干燥速率下，缓冲液的磷酸盐和盐成分之间存在协同效应，可减轻蛋白质聚集并保留蛋白质的二级和三级结构。为期90天的稳定性研究表明，在低湿度条件下储存的粉末保持了结构完整性。通过了解PBS缓冲液成分的个体稳定作用以及快速干燥时间，这些发现为喷雾干燥大型生物制品的可行性提供了有价值的见解。这种方法为制药行业开发替代冷冻干燥方法提供了一种有前景且可扩展的制剂策略，在成本、加工时间和产品稳定性方面具有优势。
