RESEARCH PAPER First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals Lucas Engelhardt 1 & Martina Röhm 2,3 & Chrystelle Mavoungou 2 & Katharina Schindowski 2 & Annette Schafmeister 2 & Ulrich Simon 1 Received: 17 October 2015 /Accepted: 8 February 2016 # Springer Science+Business Media New York 2016 ABSTRACT Purpose Aerosol particle deposition in the human nasal cav- ity is of high interest in particular for intranasal central ner- vous 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 com- plex anatomical nasal geometry. Methods Based on a standardized nasal cavity, a computa- tional fluid and particle dynamics (CFPD) model was devel- oped that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model. Results 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. Conclusions 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. KEY WORDS CFPD . nasal airflow . nose-to-brain drug delivery . olfactory cleft . standardized human nasal cavity ABBREVIATIONS BBB Blood–brain barrier CAD Computer-aided design CFPD Computational fluid and particle dynamics CNS Central nervous system CT Computed tomography DNS Direct Numerical Simulations IP Impaction parameter LES Large Eddy Simulations MMAD Mass median aerodynamic diameter NALT Nasopharynx-associated lymphoid tissue RANS Reynolds-averaged Navier–Stokes WHO World Health Organization INTRODUCTION The World Health Organization (WHO) estimates that more than a billion people worldwide are suffering from diseases of the central nervous system (CNS) (1,2). The low central avail- ability of drugs is a major hindrance of CNS therapy. The passage of most CNS-active drugs particularly of biopharmaceuticals is massively hampered by the blood– brain barrier (BBB). Molecules that do not possess a specific transport mechanism have only a chance to pass the BBB via passive diffusion. While there are at least some good examples of chemical modifications for small molecule drugs to enhance their central bioavailability, nearly all of the larger molecules such as peptides and proteins fail to cross the BBB (3). Therefore, nose-to-brain drug delivery has recently gained Lucas Engelhardt and Martina Röhm contributed equally to the manuscript and share first authorship. * Martina Röhm HBC-UU@mail.de 1 Scientific Computing Centre Ulm, Ulm University, Helmholtzstraße 20 89081 Ulm, Germany 2 Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35 88400 Biberach, Germany 3 Faculty of Medicine, Ulm University, Albert-Einstein-Allee 11 89081 Ulm, Germany Pharm Res DOI 10.1007/s11095-016-1875-7