TY - JOUR
T1 - Effects of dose loading conditions and device geometry on the transport and aerosolization in dry powder inhalers
T2 - A simulation study
AU - Sulaiman, Mostafa
AU - Liu, Xiaoyu
AU - Sundaresan, Sankaran
N1 - Funding Information:
Financial assistance for the project by the U.S. Food and Drug Administration (FDA) (Grant 1U01FD006514) is gratefully acknowledged. We gratefully acknowledge suggestions and critiques by Ross Walenga from the Office of Generic Drugs at the US FDA and Professor Ali Ozel (Heriot-Watt University) during the course of this study. Sankaran Sundaresan gratefully acknowledges the inspiration and financial support provided by the William R. and Jane G. Schowalter Research Fund and his former Ph.D. student Sanjay Dasgupta.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - 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.
AB - 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.
KW - Computational Fluid Dynamics
KW - Discrete Element Method
KW - Dose loading
KW - Dry Powder Inhaler
KW - Fine Particle Fraction
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U2 - 10.1016/j.ijpharm.2021.121219
DO - 10.1016/j.ijpharm.2021.121219
M3 - Article
C2 - 34699949
AN - SCOPUS:85118189762
SN - 0378-5173
VL - 610
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 121219
ER -