First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals



Aerosol particle deposition in the human nasal cavity is of high interest in particular for intranasal central nervous system (CNS) drug delivery via the olfactory cleft. The objective of this study was the development and comparison of a numerical and experimental model to investigate various parameters for olfactory particle deposition within the complex anatomical nasal geometry.


Based on a standardized nasal cavity, a computational fluid and particle dynamics (CFPD) model was developed that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model.


For various flow rates (5 to 40 l/min) and particle sizes (1 to 10 μm), the airflow velocities, the calculated particle airflow patterns and the particle deposition correlated very well with the experiment. Particle deposition was investigated numerically by varying particle sizes at constant flow rate and vice versa assuming the particle size distribution of the used nebulizer.


The developed CFPD model could be directly translated to the in vitro results. Hence, it can be applied for parameter screening and will contribute to the improvement of aerosol particle deposition at the olfactory cleft for CNS drug delivery in particular for biopharmaceuticals.

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Blood–brain barrier


Computer-aided design


Computational fluid and particle dynamics


Central nervous system


Computed tomography


Direct Numerical Simulations


Impaction parameter


Large Eddy Simulations


Mass median aerodynamic diameter


Nasopharynx-associated lymphoid tissue


Reynolds-averaged Navier–Stokes


World Health Organization


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This study was supported by Ulm and Biberach joint graduate school in pharmaceutical biotechnology funded by the Baden-Württemberg State Ministry of Science, Research and Arts. Special thanks go to Dr. Andreas Lintermann for his helpful support and valuable scientific comments on the manuscript.

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Correspondence to Martina Röhm.

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Lucas Engelhardt and Martina Röhm contributed equally to the manuscript and share first authorship.

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Engelhardt, L., Röhm, M., Mavoungou, C. et al. First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals. Pharm Res 33, 1337–1350 (2016).

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Key words

  • CFPD
  • nasal airflow
  • nose-to-brain drug delivery
  • olfactory cleft
  • standardized human nasal cavity