The purpose of the present study was to investigate the influence of method of preparation of large respirable particles of amikacin sulphate on traits and topography and in-vitro aerosol performance. Large respirable particles of amikacin sulfate (50%w/w) were produced by spray-drying and freeze-drying processes using hydrogenated soyaphosphatidylcholine, L-leucine and Poloxamer 188. Particles exhibited 0.04 – 0.08 g/cm3 tap densities, 7-20 μm geometric particle size, and 1 to 5 μm of mean aerodynamic diameter. Apart from the morphology and topographical features, spraydried and freeze- dried particles had marginal difference in their solid-state characteristics. Spray-dried particles were dimpled spherical shape with roundness value close to 1(1.066 ± 0.028), relatively smooth surface texture and produced greater aerosol dispersion with 20% higher fine particle fraction, 6.92% lower impaction loss and 13% less capsule and device retention than freeze dried particles. Traits and topographical features, such as particle size, polydispersity, elongation ratio, roundness, shape, and degree of surface roughness were found to be influenced significantly by spray-drying process and particles produced by spray-drying process showed better aerosol performance due to these differences.