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Peer-reviewedCC BY 4.0Pharmaceutical Research

Transnasal Administration of Surfactant Aerosol to the Lungs of Infants Using Direct Interfaces – Lessons Learned from Computational Fluid Dynamics

  • Hasan Jubaer1
  • Dale Farkas1
  • Caleb Dalton2
  • Mohammad A. M. Momin2
  • Michael Hindle2
  • Worth Longest1,2
  1. 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA 23284-3015 USA
  2. 2Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA
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Abstract

Purpose: Direct-to-infant (D2I) transnasal aerosol surfactant therapy (AST) offers a promising non-invasive alternative for treating neonatal respiratory distress syndrome (RDS). However, achieving high lung delivery efficiency with dry powder inhalers (DPIs) requires careful optimization of complex fluid–particle interactions. This study used computational fluid dynamics (CFD) to optimize an Infant Air‑Jet Dry Powder Aerosol Delivery System (iDP‑ADS) and derive transferable design principles.

Methods: A CFD model of the iDP‑ADS coupled to a 31‑week preterm nose‑throat geometry was validated against in vitro measurements. Sensitivity analyses evaluated modeling assumptions (steady‑state vs. transient, monodisperse vs. polydisperse) and critical design parameters influencing aerosol delivery, such as upstream air volume, interface geometry, temporal aerosol emission profiles, and actuation flow rates.

Results: The CFD model demonstrated strong in vitro agreement (2.8% mean absolute difference). Regarding modeling: standard simplifications, particularly steady-state approximations, overpredicted lung transmission (~24%), establishing the necessity of high-fidelity transient simulations with polydisperse aerosols. Regarding aerosol delivery: integrating an upstream air volume created "hydrodynamic shielding," reducing relative interface losses by up to 50%. A 10 mm diffusive path length and 20° (inward and downward) prong alignment balanced jet dissipation while minimizing nasal deposition. Front-loading of aerosol emission prevented entrapment of 10–14% of the dose in anatomical dead space. An optimal system-specific actuation flow rate of 3 L/min achieved ~53.5% aerosol lung transmission, balancing aerosolization efficiency against turbulence-driven transport losses.

Conclusions: High-efficiency transnasal AST requires balancing often competing aerosol generation physics, transport behavior, and clinical constraints. This study highlights CFD as a vital design tool, providing key lessons to inform future modeling and practical interface development.

Graphical Abstract:

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11095-026-04186-1.

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Cite

BibTeXRIS
BibTeX
@article{jubaer2026transnasal,
  title = {{Transnasal Administration of Surfactant Aerosol to the Lungs of Infants Using Direct Interfaces – Lessons Learned from Computational Fluid Dynamics}},
  author = {Hasan Jubaer and Dale Farkas and Caleb Dalton and Mohammad A. M. Momin and Michael Hindle and Worth Longest},
  journal = {Pharmaceutical Research},
  year = {2026},
  month = sep,
  doi = {10.1007/s11095-026-04186-1},
  url = {https://doi.org/10.1007/s11095-026-04186-1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Transnasal Administration of Surfactant Aerosol to the Lungs of Infants Using Direct Interfaces – Lessons Learned from Computational Fluid Dynamics
AU  - Hasan Jubaer
AU  - Dale Farkas
AU  - Caleb Dalton
AU  - Mohammad A. M. Momin
AU  - Michael Hindle
AU  - Worth Longest
PY  - 2026
DA  - 2026/09/03
JO  - Pharmaceutical Research
DO  - 10.1007/s11095-026-04186-1
UR  - https://doi.org/10.1007/s11095-026-04186-1
AB  - Purpose: Direct-to-infant (D2I) transnasal aerosol surfactant therapy (AST) offers a promising non-invasive alternative for treating neonatal respiratory distress syndrome (RDS). However, achieving high lung delivery efficiency with dry powder inhalers (DPIs) requires careful optimization of complex fluid–particle interactions. This study used computational fluid dynamics (CFD) to optimize an Infant Air‑Jet Dry Powder Aerosol Delivery System (iDP‑ADS) and derive transferable design principles.  Methods: A CFD model of the iDP‑ADS coupled to a 31‑week preterm nose‑throat geometry was validated against in vitro measurements. Sensitivity analyses evaluated modeling assumptions (steady‑state vs. transient, monodisperse vs. polydisperse) and critical design parameters influencing aerosol delivery, such as upstream air volume, interface geometry, temporal aerosol emission profiles, and actuation flow rates.  Results: The CFD model demonstrated strong in vitro agreement (2.8% mean absolute difference). Regarding modeling: standard simplifications, particularly steady-state approximations, overpredicted lung transmission (~24%), establishing the necessity of high-fidelity transient simulations with polydisperse aerosols. Regarding aerosol delivery: integrating an upstream air volume created "hydrodynamic shielding," reducing relative interface losses by up to 50%. A 10 mm diffusive path length and 20° (inward and downward) prong alignment balanced jet dissipation while minimizing nasal deposition. Front-loading of aerosol emission prevented entrapment of 10–14% of the dose in anatomical dead space. An optimal system-specific actuation flow rate of 3 L/min achieved ~53.5% aerosol lung transmission, balancing aerosolization efficiency against turbulence-driven transport losses.  Conclusions: High-efficiency transnasal AST requires balancing often competing aerosol generation physics, transport behavior, and clinical constraints. This study highlights CFD as a vital design tool, providing key lessons to inform future modeling and practical interface development.  Graphical Abstract:  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11095-026-04186-1.
SN  - 0724-8741
SN  - 1573-904X
ER  -