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PMID: 30556777 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Validation Study

High-Efficiency Nose-to-Lung Aerosol Delivery in an Infant: Development of a Validated Computational Fluid Dynamics Method.

Journal of aerosol medicine and pulmonary drug delivery ·Vol. 32 ·No. 3 ·2019-00-00 ·页码 132-148

Bass K, Boc S, Hindle M, Dodson K, Longest W

Abstract

Background: Computational fluid dynamics (CFD) provides a powerful tool for developing new high-efficiency aerosol delivery strategies, such as nose-to-lung (N2L) aerosol administration to infants and children using correctly sized aerosols. The objective of this study was to establish numerically efficient CFD solution methods and guidelines for simulating N2L aerosol administration to an infant based on comparisons with concurrent in vitro experiments. Materials and Methods: N2L administration of a micrometer-sized aerosol (mass median aerodynamic diameter [MMAD] = 1.4 μm) was evaluated using concurrent CFD simulations and in vitro experiments. Aerosol transport and deposition was assessed in a new nasal airway geometry of a 6-month-old infant with a streamlined nasal cannula interface, which was constructed as a CFD mesh and three-dimensionally printed to form an identical physical prototype. CFD meshes explored were a conventional tetrahedral approach with near-wall (NW) prism elements and a new polyhedral mesh style with an equally refined NW layer. The presence of turbulence in the model was evaluated using a highly efficient low-Reynolds number (LRN) k-ω turbulence model, with previously established NW corrections that accounted for anisotropic wall-normal turbulence as well as improved NW velocity interpolations and hydrodynamic particle damping. Results: Use of the new polyhedral mesh was found to improve numerical efficiency by providing more rapid convergence and requiring fewer control volumes. Turbulent flow was found in the nasal geometry, generated by the inlet jets from the nasal cannula interface. However, due to the small particle size, turbulent dispersion was shown to have little effect on deposition. Good agreement was established between the CFD predictions using the numerically efficient LRN k-ω model with appropriate NW corrections and in vitro deposition data. Aerosol transmission efficiencies through the delivery tube, nasal cannula, and infant nasal model, based on experimental and CFD predictions, were 93.0% and 91.5%, respectively. Conclusions: A numerically efficient CFD approach was established to develop transnasal aerosol administration to infants and children. Small particle aerosols with aerodynamic diameters of ∼1.5 μm were confirmed to have low inertial depositional loss, and have low deposition from turbulent dispersion, making them ideal for high-efficiency lung delivery through an infant nasal cannula interface.

Keywords
CFD aerosol simulations CFD validation excipient-enhanced growth pharmaceutical aerosol
MeSH 主题词
Administration, Inhalation Administration, Intranasal Aerosols/administration & dosage,pharmacokinetics Computer Simulation Drug Delivery Systems Equipment Design Humans Hydrodynamics Infant Lung/metabolism Models, Biological Particle Size
化学物质
Aerosols
作者与单位
共 5 位作者,点击展开单位 / ORCID
Bass Karl
1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
Boc Susan
2 Department of Pharmaceutics, and Virginia Commonwealth University, Richmond, Virginia.
Hindle Michael
2 Department of Pharmaceutics, and Virginia Commonwealth University, Richmond, Virginia.
Dodson Kelley
3 Department of Otolaryngology-Head and Neck Surgery, Virginia Commonwealth University, Richmond, Virginia.
Longest Worth
1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia. | 2 Department of Pharmaceutics, and Virginia Commonwealth University, Richmond, Virginia.
Article Info
Journal
Journal of aerosol medicine and pulmonary drug delivery
Abbr.
J Aerosol Med Pulm Drug Deliv
ISSN
1941-2703
Published
2019-00-00
电子出版
2018-00-15
页码
132-148
Language
English
Country/Region
United States
NLM ID
101475057
基金资助
NICHD NIH HHS · R01 HD087339 · United States
NHLBI NIH HHS · R01 HL139673 · United States
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