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However, achieving high lung delivery efficiency with dry powder inhalers (DPIs) requires careful optimization of complex fluid\u2013particle interactions. This study used computational fluid dynamics (CFD) to optimize an Infant Air\u2011Jet Dry Powder Aerosol Delivery System (iDP\u2011ADS) and derive transferable design principles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A CFD model of the iDP\u2011ADS coupled to a 31\u2011week preterm nose\u2011throat geometry was validated against\n                      <jats:italic>in vitro<\/jats:italic>\n                      measurements. Sensitivity analyses evaluated modeling assumptions (steady\u2011state 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The CFD model demonstrated strong\n                      <jats:italic>in vitro<\/jats:italic>\n                      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\u00a0mm diffusive path length and 20\u00b0 (inward and downward) prong alignment balanced jet dissipation while minimizing nasal deposition. Front-loading of aerosol emission prevented entrapment of\u00a010\u201314% of the\u00a0dose in anatomical dead space. An optimal system-specific actuation flow rate of 3 L\/min achieved\u2009~53.5% aerosol lung transmission, balancing aerosolization efficiency against turbulence-driven transport losses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11095-026-04186-1","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:42:30Z","timestamp":1788396150000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transnasal Administration of Surfactant Aerosol to the Lungs of Infants Using Direct Interfaces \u2013 Lessons Learned from Computational Fluid Dynamics"],"prefix":"10.1007","author":[{"given":"Hasan","family":"Jubaer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale","family":"Farkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A. 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