Room Temperature Aerosol Dehydration 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 sub-20 μm droplets that quickly evaporate at ambient temperature, which reduce drying-induced stress for thermally sensitive biologics. In this work, we used green fluorescence protein (GFP) as a model biological molecule to optimize the RTAD system design. We studied the effects of polysorbate 20 (a model surfactant), droplet size, and the flow pattern in the drying chamber on GFP fluorescence after drying and powder reconstitution. We found that the presence of polysorbate 20 in the formulation has a significant impact on the GFP fluorescence, especially for smaller droplets. GFP fluorescence is also affected by the flow pattern in the drying chamber as revealed by Computational Fluid Dynamics (CFD) simulations. We found that non-axisymmetric flow patterns and closed circulating streamlines near the drying gas inlet can negatively affect the GFP fluorescence. The work reported here demonstrates GFP as a sensitive biologic for assessing bioactivity following dehydration processing, which can be used for efficient development novel RTAD drying process.