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This article discusses CFD simulations of nasal spray transport and use of CFD modeling to design nasal spray devices and analyze spray delivery performance. In silico testing using CFD, guided with in vitro measurements, is a potentially valuable approach that can reduce time and costs of evaluating nasal spray delivery performance under variable usage conditions in realistic nasal airway models. 10 June 2022 Inhalation Use of computational fluid dynamics (CFD) modeling for design and performance analysis of nasal sprays A short perspective on nasal spray CFD simulations and use of CFD modeling to design nasal spray devices and analyze spray delivery performance Arun V. Kolanjiyil, PhD and Worth Longest, PhD Virginia Commonwealth University ditions and actuation force, and the nasal geometry, which is known to be highly variable [2, 6-13]. Knowledge of drug delivery performance of nasal spray pumps under variable usage conditions is important to facilitate device design improvements and to develop new administration protocols that can enhance posterior delivery efficiency and drug targeting. Furthermore, quantifying the delivered dose and its variability under different usage condi- tions may be important for assisting in the develop- ment of generic products and, in the future, could also be used in the evaluation of those generic prod- ucts for bioequivalence. Considering nasal spray test- ing, in vitro methods and experimental visualization techniques are available to characterize the spray and/ or approximate regional nasal deposition [14, 15]. At the same time, in silico studies of spray droplet trans- port and deposition in nasal airway models using computational fluid dynamics (CFD) simulations can provide detailed and sometimes enhanced infor- mation on device performance and nasal deposition [16, 17]. Additionally, CFD simulations validated with in vitro experimental measurements can be used as a research tool to analyze the effect of product and usage variability while limiting time and cost asso- ciated with extensive in vitro testing and/or in vivo human subject testing [5, 10, 12, 18]. Computational fluid dynamics (CFD) CFD is a computational modeling technique widely used to develop, test and improve engineering sys- Introduction Nasal spray pumps are a common device choice to administer locally acting drugs for the treatment of allergic rhinitis, sinusitis and nasal polyposis. Deliv- ering nasally-targeted pharmaceutical formulations using spray pumps has many advantages compared with oral administration including fast onset of action and avoidance of first-pass metabolism. ere is also increasing interest in the use of nasal sprays to deliver vaccines, drugs requiring rapid absorption into the systemic circulation, or drugs intended for the central nervous system. Most nasal spray pumps are hand- actuated, which forces the formulation through a spray nozzle and results in atomization of the liquid. ese spray products are intended to deliver drugs and other therapeutics primarily to the posterior nasal region (which resides behind the anterior nose and nasal valve) while limiting drug penetration into the lungs. erefore, nasal spray products are designed to produce relatively large droplets (20-200 µm) that enter the nose with relatively high velocity [1-3]. Due to the large spray droplet size and high spray velocity, these droplets carry significant momentum that can result in enhanced momentum exchange with the gas phase in the droplet-dense region surrounding the spray nozzle [1, 4]. As a result, a cloud motion effect is generated, which remains one of the more challenging problems of multiphase flow physics [5]. e delivery efficiency of nasal spray products to the posterior nasal region depends on many factors including device design, drug formulation proper- ties, patient-related factors such as inhalation con-

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