Abstract: Purpose: To examine the potential to engineer a new formulation platform for delivering biomolecules to the lung: a design of experiments approach to determine the impact of adding amino acids (leucine, glycine and alanine) on the dispersibility and morphology of a mannitol-based spray-dried powder formulation. Methods: A range of compositions comprising mannitol and varying amino acids were spray-dried. A 2³ factorial design in which 3 amino acids selected for varying hydrocarbon chain length were added to control specific properties of the formulations. The aerosolisation efficiency was assessed by dispersing the powders from a Monodose inhaler into a Spraytec laser diffraction system. The morphology of the particles was examined under scanning electron microscope (SEM). Results: The mannitol had a median volume equivalent diameter of 2.8 (±0.1) µm while the formulations containing amino acid additives were mostly larger in laser diffraction measured diameter, although the DoE central point formulations containing leucine, glycine and alanine as additives demonstrated the smallest median diameter of 2.4 (±0.3) µm. The particles containing leucine, with or without others provided relatively efficient aerosolisation, but particle shape revealed distinctive morphological features. However, particles with alanine and/or glycine were more substantially agglomerated, and less easily dispersed. Conclusion: This DoE approach clearly identified the beneficial impact of inclusion of leucine on the aerosol performance and morphology of the formulations. The benefit provided by the leucine appears associated with its enrichment at the particle surface, as well as impact on particle morphology.