The human lung is an effective route for noninvasive drug delivery because it provides a large surface area for rapid absorption, a minimal physical barrier, an absence of extreme pH and metabolism, no first-pass liver, a rich blood supply, and poor bioavailability of oral drugs. The physical and electrical properties of active pharmaceutical ingredient and excipient interactively influence 5 electromechanical deposition mechanisms of respiratory medicinal aerosols while flowing through the airways, including nose, mouth, pharynx, trachea, bronchi, bronchioles, and alveoli.

The therapeutic particles from a specific device during the inhalation process come out as an aerosolized form. The dispersion of these pharmaceutical powders is often difficult because the fine powders are cohesive as a result of the strong interparticle adhesion forces: van der Waals, capillary, and electrostatic attractions. Typically, cohesive forces are proportional to the diameter d of the particles, whereas the detachment forces for resuspending the particles forming aerosol are proportional to d2 when aerodynamic shear force is used for the dispersion. Thus, the smaller the diameter, the higher the shear force needed for efficient dispersion to form aerosol containing the primary active pharmaceutical ingredient and excipient particles micronized in the jet mill. A solution to these problems can be the manufacture of engineered active pharmaceutical ingredient and excipient to manipulate the cohesivity and dispersibility with necessary magnitudes of particle charge during the micronization process. These modifications will improve blending uniformity and long-term stability of the powder mixtures.