TY - JOUR
T1 - Estimating inter-patient variability of dispersion in dry powder inhalers using CFD-DEM simulations
AU - Benque, Benedict
AU - Khinast, Johannes G.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Drug delivery from a capsule-based dry powder inhaler depends on the inhaler's design, the drug's formulation, and the inhalation maneuver. The latter affects both the air flow and the capsule motion in the inhaler. It is well known that patient-to-patient variability is a major challenge in the design of new inhaler types. Modeling and simulation are important tools for understanding such systems, yet quite complex. Simulation studies of capsule-based dry powder inhalers have disregarded the transient nature of the inhalation process, adopting a constant flow rate through the inhaler instead. In addition, either no capsules, a capsule in a fixed position, or a capsule rotating at a constant rate have been considered. In this work, literature data for three inhalation flow profiles were incorporated into coupled simulations of the air flow and carrier particle motion through an Aerolizer® dry powder inhaler with a rotating capsule and compared to simulations at constant air flow rates. The results for the profile simulations indicated that the carrier powder experienced larger velocity fluctuations. Acceleration events were tracked as a measure of collision- and flow-induced dispersion. The majority of fast particle accelerations occurred when the particles collided with the swirl chamber walls. Of the two common particle dispersion metrics, only the peak particle force distribution appeared to be sensitive to the inhalation profiles, while the effect of the profiles on the cumulative impulse was small.
AB - Drug delivery from a capsule-based dry powder inhaler depends on the inhaler's design, the drug's formulation, and the inhalation maneuver. The latter affects both the air flow and the capsule motion in the inhaler. It is well known that patient-to-patient variability is a major challenge in the design of new inhaler types. Modeling and simulation are important tools for understanding such systems, yet quite complex. Simulation studies of capsule-based dry powder inhalers have disregarded the transient nature of the inhalation process, adopting a constant flow rate through the inhaler instead. In addition, either no capsules, a capsule in a fixed position, or a capsule rotating at a constant rate have been considered. In this work, literature data for three inhalation flow profiles were incorporated into coupled simulations of the air flow and carrier particle motion through an Aerolizer® dry powder inhaler with a rotating capsule and compared to simulations at constant air flow rates. The results for the profile simulations indicated that the carrier powder experienced larger velocity fluctuations. Acceleration events were tracked as a measure of collision- and flow-induced dispersion. The majority of fast particle accelerations occurred when the particles collided with the swirl chamber walls. Of the two common particle dispersion metrics, only the peak particle force distribution appeared to be sensitive to the inhalation profiles, while the effect of the profiles on the cumulative impulse was small.
KW - Dry powder inhaler
KW - Inhalation profile
KW - Computational fluid dynamics
KW - Discrete element method
KW - Carrier particle
KW - Capsule motion
UR - http://www.scopus.com/inward/record.url?scp=85091961243&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2020.105574
DO - 10.1016/j.ejps.2020.105574
M3 - Article
VL - 156
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
M1 - 105574
ER -