Both active pharmaceutical ingredients (API) and ternary components such as lactose, commonly used in dry powder inhaler (DPI) formulations, are micron-sized and form cohesive matrices due to interparticulate interactions. In powder mixtures, these cohesive structures may be complex depending on the propensity of the cohesive-adhesive interactions of the materials. The de-agglomeration and aerosolization of these cohesive matrices are essential for effective delivery to the lower respiratory tract, the principal target of most respiratory drug delivery treatment. Although the target particle size of de-agglomerated powders is determined by the utilization purpose, it should be less than 5 I?m for deposition in the lower respiratory tract. The factors influencing the complex de-agglomeration process have been a focus of research for better formulation design.