Three-dimensional DEM–CFD analysis of air-flow-induced detachment of API particles from carrier particles in dry powder inhalers

Abstract

Air flow and particle–particle/wall impacts are considered as two primary dispersion mechanisms for dry powder inhalers (DPIs). Hence, an understanding of these mechanisms is critical for the development of DPIs. In this study, a coupled DEM–CFD (discrete element method–computational fluid dynamics) is employed to investigate the influence of air flow on the dispersion performance of the carrier-based DPI formulations. A carrier-based agglomerate is initially formed and then dispersed in a uniformed air flow. It is found that air flow can drag API particles away from the carrier and those in the downstream air flow regions are prone to be dispersed. Furthermore, the influence of the air velocity and work of adhesion are also examined. It is shown that the dispersion number (i.e., the number of API particles detached from the carrier) increases with increasing air velocity, and decreases with increasing the work of adhesion, indicating that the DPI performance is controlled by the balance of the removal and adhesive forces. It is also shown that the cumulative Weibull distribution function can be used to describe the DPI performance, which is governed by the ratio of the fluid drag force to the pull-off force.

DEM analysis of the effect of particle–wall impact on the dispersion performance in carrier-based dry powder inhalers

“…In the current DEM, particle-particle and particle-wall interactions are modelled using theoretical contact mechanics, in which physical properties such as Young's modulus, Poisson's ratio, particle density, coefficient of friction are the input parameters and surface energy is chosen as a varying parameter for the sensitivity analysis. As a first approximation, the carrier and API particles are assumed to be spherical and of the same material, which is consistent with that used in our previous studies (Yang et al 2013(Yang et al , 2014(Yang et al , and 2015. Even so, it is still believed that the present study will enhance our understanding of the underlying micromechanics of dispersion process in DPIs.…”

“…The polar histograms (Zhang 2003) for the contact orientation distribution are used to illustrate the preferential location for the API particles to detach from the carrier. The method to obtain the polar histograms can be found in our previous work (Yang et al 2014). The radius of each triangular band represents the residual ratio of API particles on that carrier surface area, i.e.…”

“…The dispersion performance can also be approximated using the same cumulative Weibull distribution function as proposed in the previous work for airflow induced dispersion (Yang et al 2014): The above energy analysis is based on a single API particle. If the carrierbased agglomerate is considered as a whole, the normal impact energy is:…”

“…DEM is well recognized as a useful tool to explore fundamental mechanisms since it provides the detailed information of particles positions, velocities, and the transient forces acting on particles, which correlates the macroscopic behaviour with microscopic interactions (Zhu, Zhou et al, 2007;Zhu, Zhou et al, 2008). The DEM code used has been validated by theory and for many applications (Guo, Wu et al, 2013;Thornton and Yin, 1991) and it has also been proved capable of modelling DPIs, as the effects of van der Waals force (Yang, Wu et al, 2013), electrostatic force (Yang, Wu et al, 2015), and drag force caused by air flow (Yang, Wu et al, 2014) could be considered. Nevertheless, further study with a more realistic model shall be performed to provide a comprehensive understanding of dry powder inhalation.…”

Breakage of wet flexible fiber agglomerates impacting a plane

“…For example, pharmaceutical dry powder inhalers sometimes use carrier‐based agglomerates consisting of large carrier particles and small drug particles, but can also use agglomerates formed only by small drug particles. Agglomerates can be broken due to the drag of surrounding fluids, the impact between agglomerates, and/or the adhesion between an agglomerate and the wall of a device . Different types of agglomerates are reported to have different breakage behaviors, which may result from differences in agglomerate structure and constituent particle properties .…”