LAUSR

&NA; The aim of this study was to identify critical steps to protein stability during spray drying using two different nozzle types: a vibrating mesh nozzle and a standard two‐fluid nozzle in a Büchi B‐90 spray dryer. L‐Lactic dehydrogenase was used as a model protein as it is a heat and shear stress sensitive protein. Trehalose was used as excipient because of its excellent stabilizing capacities. The entire spray drying process was split up into smaller steps and after each step the enzymatic activity of the protein was measured. With the vibrating mesh nozzle in total 78% of activity was lost. About 68% was due to atomizing and heating and 10% was caused by dehydration and circulation of the liquid. With the two‐fluid nozzle the total activity loss was only 23%, to which atomization, dehydration, and circulation contributed almost equally. Heating was not an issue, as the two‐fluid nozzle could be cooled with water. In conclusion, the type and the configuration of the nozzle used for spray drying are important determinants for maintaining protein stability, as atomizing, heating, ultra‐sonication, and recirculation of the feed solution negatively influence it. The possibility to cool the two‐fluid nozzle offers an important advantage to the vibrating mesh nozzle in the spray drying process of proteins. In this study, we show that, next to the optimization of the formulation, optimization of the spray drying process should be taken into account to maintain protein stability.