Particle-based coarse-grained approach for simulating dry powder inhaler

Abstract

Drug delivery via dry powder inhaler (DPI) is a complex process affected by multiple factors involving gas and particles. The performance of a carrier-based formulation depends on the release of active pharmaceutical ingredient (API) particles, typically characterized by fine particle fraction (FPF) and dispersion fraction (DF). Computational Fluid Dynamics coupled with Discrete Element Method (CFD-DEM) can capture relevant gas and particle interactions but is computationally expensive, especially when tracking all carrier and API particles. This study assessed the efficacy of two coarse-grained CFD-DEM approaches, the Discrete Parcel Method and the representative particle approach, through highly-resolved CFD-DEM simulations. The representative particle approach simulates all carrier particles and a subset of API particles, whereas the Discrete Parcel Method tracks parcels representing a specified number of carrier or API particles. Both approaches are viable for a small carrier-API size ratio which requires modest degrees of coarse-graining, but the Discrete Parcel Method showed limitations for a large carrier-API size ratio. The representative particle approach can approximate CFD-DEM results with reasonable accuracies when simulations include at least 10 representative API particles per carrier. Using the representative particle approach, we probed powder characteristics that could affect FPF and DF in a model problem and correlated these fractions with the maximum carrier-API cohesive force per unit mass of API particles.