The aim of this work was to investigate the mechanistic evaluation of aerosolization properties of new engineered lactose obtained from binary mixtures of butanol:acetone from DPI formulations containing salbutamol sulphate . Compared to commercial lactose, crystallised lactose particles were less elongated, covered with fine lactose particles, and had a rougher surface morphology. The crystallised lactose powders had a considerably lower bulk and tap densities and poorer flow when compared to commercial lactose. Engineered carrier with better flow showed improved drug content homogeneity, reduced amounts of drug “deposited” on the inhaler device and throat, and a smaller drug aerodynamic diameter upon inhalation. Aerodynamic diameter of salbutamol sulphate (SS) increased as lactose aerodynamic diameter decreased (linear relationship, R2=0.9191) and/or as fine particle lactose content increased (linear relationship, R2=0.8653). Among all lactose samples, lactose particles crystallised from pure butanol generated the highest aerosolization performance for DPI containing salbutamol sulphate.