DEM analysis of the effect of electrostatic interaction on particle mixing for carrier-based dry powder inhaler formulations

Particle interactions play a significant role in controlling the performance of dry powder inhalers (DPIs), which mainly arise through van der Waals potentials, electrostatic interactions, and capillary forces. Our aim is to investigate the influence of electrostatic charge on the performance of DPIs as a basis for improving the formulation of the particle ingredients. The mixing process of carrier and active pharmaceutical ingredient (API) particles in a vibrating container is investigated using a discrete element method (DEM). The number of API particles attaching to the carrier particle (i.e., contact number) increases with increasing charge and decreases with increasing container size. The contact number decreases with increasing vibrational velocity amplitude and frequency. Moreover, a mechanism governed by the electrostatic force is proposed for the mixing process. This mechanism is different from that previously proposed for the mixing process governed by van der Waals forces, indicating that long-range and short-range adhesive forces can result in different mixing behaviours.