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1.
Chem Pharm Bull (Tokyo) ; 68(8): 726-736, 2020.
Article in English | MEDLINE | ID: mdl-32741913

ABSTRACT

This study investigated the particle adhesion mechanism in a capsule of dry powder inhaler (DPI) based on a combined computational fluid dynamics and discrete element method (CFD-DEM) approach. In this study, the Johnson-Kendall-Roberts (JKR) theory was selected as the adhesion force model. The simulation results corroborated the experimental results-numerous particles remained on the outlet side of the capsule, while a few particles remained on the inlet side. In the computer simulation, the modeled particles were placed in a capsule. They were quickly dispersed to both sides of the capsule, by air fed from one side of the capsule, and delivered from the air inlet side to the outlet side of the capsule. It was confirmed that vortex flows were seen at the outlet side of the capsule, which, however, were not seen at the inlet side. Numerous collisions were observed at the outlet side, while very few collisions were observed at the inlet side. These results suggested that the vortex flows were crucial to reduce the amount of residual particles in the capsule. The original capsule was then modified to enhance the vortex flow in the area, where many particles were found remaining. The modified capsule reduced the number of residual particles compared to the original capsule. This investigation suggests that the CFD-DEM approach can be a great tool for understanding the particle adhesion mechanism and improving the delivery efficiency of DPIs.


Subject(s)
Computer Simulation , Dry Powder Inhalers/methods , Capsules/chemistry , Dry Powder Inhalers/instrumentation , Equipment Design , Hydrodynamics , Hypromellose Derivatives/chemistry , Mannitol/administration & dosage , Mannitol/chemistry , Particle Size , Powders/chemistry
2.
Chem Pharm Bull (Tokyo) ; 67(12): 1328-1336, 2019.
Article in English | MEDLINE | ID: mdl-31787659

ABSTRACT

Dry powder inhalation (DPI) has attracted much attention as a treatment for respiratory diseases owing to the large effective absorption area in a human respiratory system. Understanding the drug particle motion in the respiratory system and the deposition behavior is necessary to improve the efficiency of DPI. We conducted computer simulations using a model coupling a discrete element method and a computational fluid dynamics method (DEM-CFD) to evaluate the particle deposition in human respiratory system. A simple artificial respiratory model was developed, which numerically investigated the effect of particle properties and inhalation patterns on the particle deposition behavior. The DEM-CFD simulations demonstrated that the smaller- and lower-density particles showed higher reachability into the simple respiratory model, and the particle arrival ratio to the deep region strongly depended on the aerodynamic diameter. The particle arrival ratio can be described as an exponential function of the aerodynamic diameter. Furthermore, the exponential relationship between the particle reachability into the depth of the simple respiratory model and the aerodynamic diameter predicted the particle aerodynamic diameter based on the required reachability. The particle shape also had an impact on the particle deposition behavior. The rod-like particles with a larger aspect ratio indicated higher reachability into the depth of the simple respiratory model. This was attributed to the high velocity motion of the particles whose long axis was in the direction of the deep region.


Subject(s)
Dry Powder Inhalers , Respiratory System/chemistry , Administration, Inhalation , Drug Delivery Systems , Humans , Hydrodynamics , Particle Size
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