Coarsening
approach in modeling gas-particle flows in dry powder inhaler

X. Liu¹,
J. Kolehmainen¹, S. Sundaresan¹

¹Department of Chemical and Biological Engineering,
Princeton University, Princeton, New Jersey 08540, USA

Dry powder inhaler (DPI) is commonly used to treat
respiratory diseases by delivering active pharmaceutical ingredient (API)
particles to the airways and/or lungs of the patient [1]. Because of the strong
cohesive interaction between small API particles, larger carrier particles are
utilized to agglomerate with API particles so as to improve fluidization, and
then deagglomerate to release API particles for drug delivery [2-3]. Computational
fluid dynamics coupled with discrete element method (CFD-DEM) has the advantage
of capturing relevant particle-fluid and particle-particle interactions in this
system but is limited by the simulation size [4]. For example, a typical DPI
simulation requires tracking a few hundred thousand carrier particles and about
ten million API particles [4]. Rigorous coarsening of the simulation to speed
up the computations would rapidly expand the use of simulations to guide the
development of DPI formulations and more efficient drug delivery.

With this in mind, the present study explores a coarsening
approach, which tracks all the carrier particles, but only a subset of
representative API particles. Such coarse-graining has been used in other contexts
(for example, see [5]). The merits and limitations of this coarse-graining
approach will be discussed in this presentation.

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Islam, N., Gladki, E. Dry powder inhalers (DPIs)—a review of device reliability
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360(1-2): 1.

[2] Yang, J., Wu, C. Y.,
Adams, M. Numerical modelling of agglomeration and deagglomeration in dry
powder inhalers: A review. Curr. Pharm.
Des. 2015; 21(40): 5915.

[3] Newman, S. P., Chan,
H. K. In vitro/in vivo comparisons in pulmonary drug delivery. J Aerosol Med Pulm Drug Deliv. 2008; 21(1):
77.

[4] van Wachem, B.,
Thalberg, K., Remmelgas, J., Niklasson‐Björn, I. Simulation of dry powder
inhalers: Combining micro‐scale, meso‐scale and macro‐scale modeling. AIChE J. 2017; 63(2): 501.

[5] Derksen, J. J.,
Sundaresan, S., Van Den Akker, H. E. A. Simulation of mass-loading effects in
gas–solid cyclone separators. Powder
Technol. 2006; 163(1-2): 59.