This paper presents the mouthpiece design geometry and powder mixture homogeneity effects of three respiratory drug delivery devices (RDDDs) to the aerodynamic and electromechanical properties of generated inhalable submicron particles. These devices are commonly known as dry powder inhalers (DPIs). Currently, DPI is considered as the preferred type of pulmonary drug administration device with the greatest potential for other biomedical applications. The aerosolized submicron particles generation and inhalation from the DPIs gained much attention in the late 1980s when Montreal protocol was designed to discourage production of chlorofluorocarbons (CFC) propellant, a widely used aerosolization component in the popular metered dose inhaler. Montreal protocol on controlling ozone depleted CFC chemicals became a major drive for the design and manufacturing technology of the DPI. The successful delivery of drugs into the deep lung depends on various aerodynamic and electromechanical properties of generated particles from the devices. Effects of the mechanistic behaviors of the DPI design geometry, and integration between device performance and powder formulations are warranted to be investigated. An electronic single particle aerodynamic relaxation time analyzer, which functions on the Laser Doppler Velocimetry principal, was employed to measure submicron particles’ charge and size in real time. Analyzed results revealed that the generated aerosol particles from all three DPIs were found to not only have different size distributions but also varied in their charge distributions. The net charge to mass ratio of DPI 1, 2, and 3 particles were 3.80 µC/g, 1.37 µC/g, and 1.45 µC/g, respectively. Count and mass distributions of the particles were reproducible (p