title: First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals.
abstract: 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.
authors.affiliation: Scientific Computing Centre Ulm, Ulm University, Helmholtzstraße 20, 89081, Ulm, Germany.
authors.forename: Lucas
authors.initials: L
authors.lastname: Engelhardt
authors.affiliation: Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany. HBC-UU@mail.de.|Faculty of Medicine, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. HBC-UU@mail.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Röhm
authors.affiliation: Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Mavoungou
authors.affiliation: Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schindowski
authors.affiliation: Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schafmeister
authors.affiliation: Scientific Computing Centre Ulm, Ulm University, Helmholtzstraße 20, 89081, Ulm, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Simon
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols; D001702:Biopharmaceutics / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008953:Models, Anatomic; D008954:Models, Biological; D065588:Nasal Absorption; D009296:Nasal Cavity / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D009716:Numerical Analysis, Computer-Assisted; D009830:Olfactory Bulb / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012212:Rheology; D013678:Technology, Pharmaceutical / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D000336:Aerosols; D004364:Pharmaceutical Preparations
keywords: CFPD; nasal airflow; nose-to-brain drug delivery; olfactory cleft; standardized human nasal cavity