Optimization of Interfacial and Mechanical Stresses during Room Temperature Aerosol Dehydration (RTAD) of Green Fluorescence Protein*

Rapid Room-Temperature Aerosol Dehydration (RTAD) is a new, scalable drying technology for pharmaceutical drug products. Compared to conventional spray drying, RTAD uses smaller droplets that quickly evaporate in ambient temperature, reducing thermal stress for thermally sensitive biologics. In this work, we used green fluorescence protein (GFP) as a model molecule of protein biologics to optimize the RTAD design. We studied the effects of surfactant, droplet size, and flow pattern on GFP fluorescence after drying and reconstitution. We found that the surfactant has a significant impact on the GFP fluorescence, especially when the droplet size is small. GFP fluorescence was also found to be affected by the flow pattern in the drying chamber. Using Computational Fluid Dynamics (CFD) simulations, we identified localized high-speed flow that creates strong circulation zones in the drying chamber, resulting in lower GFP fluorescence.