Inhalable formulations of medicines intended to act locally in the lung are therapeutically effective at lower doses with targeted delivery, compared to parenteral or oral administration. Meanwhile, different APIs, including biologics, have proven to be challenging regarding formulation and final bioavailability. This study focuses on the production, improved stability performance, and delivery of spray-dried, inhalable protein powders to the lungs. By spray-drying 11 aqueous formulations of proteinX with varying L-leucine content and by employing a Design of Experiment (DoE), two formulations have been selected for stability studies based on the highest fine particle fraction (FPF), highest monomer content, and lowest particle size. We found that 5 %w/w L-leucine (based on protein content) resulted in similar or higher FPF at 2–8 °C and 25 °C/60 %RH (67.12 % and 48.50 %) stored for six months than 10 %w/w L-leucine (68.49 % and 35.04 %). This indicates that less leucine may be sufficient to produce stable, spray-dried inhalable particles with an improved FPF, and by doubling the leucine content, the aerosolization stability can deteriorate. We have discussed the postulated hypothesis underlying the observed stability behavior based on solid-state and morphological analysis. Our results suggest that spray-dried proteinX-leu-powders can be delivered to the lung at a lower dose than for intravenous administration.