Exploration of Electrostatics Effect on Dispersion and Coating Mechanisms in Dry Powder Inhalers by Discrete Element Method

Abstract

Improving drug delivery in the respiratory system relies on the effective coating and dispersion of active pharmaceutical ingredients (APIs) in dry powder inhalers (DPIs) and the respiratory system's airways. This study aims to explore the impact of different factors on coating APIs on carrier particles, considering electrostatic and van der Waals forces using the discrete element method (DEM). This study focuses on the critical elements of API dispersion, specifically collisions between API-coated carrier particles with each other and DPI walls. The factors influencing the dispersion ratio in these collisions, such as impact velocity, contact angle, and particle charge, are examined. Additionally, a reduced-scale shaking DPI with three frequencies is used to investigate the API coating mechanism on carriers, which was not explored in previous studies. The difference in work function between carrier particles and APIs generates charge in the shaking DPI due to collisions. This causes electrostatic force to dominate over van der Waals force, breaking agglomerates and attaching APIs to carrier particles. This study shows that the amount of generated charge increases with particle collisions and that charge distribution becomes more balanced over time through charge exchange between particles. By elucidating the relationships among impact velocity, dispersion ratio, shaking frequency, and contact angles, this study paves the way for future research on more efficient DPI designs.