Modeling Complex Particle Interactions in Dry Powder Inhaler Based Drug Delivery

项目摘要

Project Abstract Title: Modeling complex particle interactions in dry powder inhaler based drug delivery. Abstract: Dry powder inhalers (DPIs) are used to deliver drugs directly to human airways and lungs, and are often used to treat medical conditions such as asthma or emphysema. The active drug particles used in DPIs are often very small, typically less than 5 micrometers. The small size makes them very cohesive, which reduces their flowability. Large carrier particles that aggregate with the smaller drug particles are employed to facilitate drug delivery. The agglomeration and deagglomeration processes that are central to DPI drug delivery are affected by a variety of factors including inter-particle cohesion due to van der Waals interaction, Coulombic and dielectrophoretic forces between charged particles and turbulence in the inhaler and human airways. Accurate modeling of fluid flow and particle motion, accounting for all these forces, is vital for thorough understanding of drug delivery using DPIs. Coulombic forces between charged particles have been widely studied in the particle technology literature; however, dielectrophoresis, which has been shown to play an essential role in clustering of seemingly identical dielectric particles, has received much less attention. As the drug and carrier particles used in DPI are usually dielectric materials, dielectrophoresis is very likely to play a significant role in agglomeration in DPIs. Including this force in DPI analysis for the first time in the literature would be a novel aspect of the proposed work. The main challenge in modeling electrostatic forces between particles lies in determining the particle charge that originates from contact charging between the particles and the device internals. Prior DPI studies have simply specified the charges on the particles, which are usually not known. The most widely used approach in literature to model the extent of particle charging via contact charging employs effective work function of each material as a phenomenological parameter to characterize charge transfer between two contacting surfaces. This approach has been employed in the research group of the PIs to study the interplay of gas-particle fluidization and particle charging; the proposed research would introduce this approach to DPI studies for the first time in the literature. In this proposal, we will develop a CFD-DEM simulation tool based on open-source platforms. Emphasis will be based on implementing models for all the known physics, including van der Waals force, fluid turbulence, Coulombic and dielectrophoretic forces and contact charging. The code will be validated against experimental data from the literature and also used to perform simulations exploring the importance of various physical characteristics of the particles.