A CFD-DEM investigation of powder transport and aerosolization in ELLIPTA® dry powder inhaler.

We have performed Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) simulations of air and particles in a commercial ELLIPTA® inhaler. We simulated the fluidization, deagglomeration and transport of carrier and API particles, with two realistic inhalation profiles that are representative of moderate asthma and very severe COPD patients, and three different mouthpiece designs. In each of the ten cases simulated, we determined the fine particle fraction (FPF) in the stream leaving the mouthpiece, the temporal evolution of the spatial distribution of the particles, the mean air (slip) velocity seen by the carrier particles, and the average numbers and normal impact velocities of carrier-carrier and carrier-wall collisions inside the inhaler. In the cases examined, the air-carrier and carrier-carrier interactions affected the FPF, while the carrier-wall interactions were too infrequent to have a substantial effect. The simulations revealed the benefit of loading both blisters even when only a single medication needs to be delivered.

Recent developments in the computational simulation of dry powder inhalers.

This article reviews recent developments in computational modeling of dry powder inhalers (DPIs). DPIs deliver drug formulations (sometimes blended with larger carrier particles) to a patient's lungs via inhalation. Inhaler design is complicated by the need for maximum aerosolization efficiency, which is favored by high levels of turbulence near the mouthpiece, with low extrathoracic depositional loss, which requires low turbulence levels near the mouth-throat region. In this article, we review the physical processes contributing to aerosolization and subsequent dispersion and deposition. We assess the performance characteristics of DPIs using existing simulation techniques and offer a perspective on how such simulations can be improved to capture the physical processes occurring over a wide range of length- and timescales more efficiently.

Effects of dose loading conditions and device geometry on the transport and aerosolization in dry powder inhalers: A simulation study.

The transport and aerosolization of particles are studied in several different dry powder inhaler geometries via Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) simulations. These simulations combine Large Eddy Simulation of gas with Discrete Element Model simulation of all the carrier particles and a representative subset of the active pharmaceutical ingredient (API) particles. The purpose of the study is to probe the dominant mechanism leading to the release of the API particles and to demonstrate the value of the CFD-DEM simulations where one tracks the motion of all the carrier and API particles. Simulations are performed at different inhalation rates and initial dose loading conditions for the screen-haler geometry, a simple cylindrical tube inhaler, and five different geometry modifications that took the form of bumpy walls and baffles. These geometry modifications alter the residence time of the powder sample in the inhaler, pressure drop across the inhaler, the severity of gas-carrier interactions, and the number of collisions experienced by the carrier particles, all of which are quantified. The quality of aerosolization is found to correlate with the average air-carrier slip velocity, while collisions played only a secondary role. Some geometry modifications improved aerosolization quality with very little increase in the pressure drop across the device.

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

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.

Numerical modelling of long flexible fibers in homogeneous isotropic turbulence.

We numerically investigated the transport, deformation and buckling events of an isolated elastic fiber in Taylor-Green vortices and studied the dynamics of long filaments in homogeneous isotropic turbulence. The fiber is modelled by an assembly of spherical beads. The contact between beads enforces the inextensibility of the filament while bending is accounted for by the Gears Bead Model (GBM) proposed by Delmotte et al. (2015). In the cellular Taylor-Green flow, the buckling probability is a function of a dimensionless number, called Sperm number, which is a balance between the compression rate of the flow and the elastic response of the filament. The shapes of the filament and its ability to buckle have been successfully validated through comparisons with experiments from the work by Quennouz et al. (2015). The deformation statistics of long flexible fibers in sustained homogeneous isotropic turbulence were analyzed for various flow and fiber material conditions. Two regimes have been identified depending on the ratio of fiber length to persistence length which is a measure of turbulent forcing to flexibility. The numerical results are in good agreement with existing experimental data (C. Brouzet et al., Phys. Rev. Lett. 112, 074501 (2014)) validating the assumptions of our model for the configurations we investigated.