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Marit Kleven

Bio: Marit Kleven is an academic researcher from Telemark University College. The author has an hindex of 1, co-authored 1 publications receiving 8 citations.

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Journal ArticleDOI
TL;DR: The accuracy and value of CFD for the study of drug delivery design to the nose is reviewed in comparison to experimental results with other methods and some important challenges when dealing with grid generation and flow simulations in these complex geometries with variable multiphase flow patterns in alternate directions are discussed.
Abstract: Computer fluid dynamics (CFD) has for many years now been employed to study and solve fluid problems in the industry and offers an attractive method for accurately describing systems at a reasonable cost Computer-aided methods are becoming increasingly important in medicine Due to a combination of increased computer efficiency and advanced numerical techniques, the realism of these simulations has been enhanced in recent years Over the past decade, computer-aided design has emerged as a method that is both sufficiently rigorous and efficient to be used for studies of the fluid dynamics in complex airway structures like the nasal airway Physical experiments in vitro and in vivo are often expensive and time-consuming, and CFD has gained increasing attention as a tool in the design process of devices delivering drugs to the respiratory tract This paper provides a review of the development of CFD in the studies of nasal airway fluid dynamics, particle and filtering properties in health and disease Special emphasis is given to studies related to CFD studies used in the development of nasal drug delivery devices The accuracy and value of CFD for the study of drug delivery design to the nose is reviewed in comparison to experimental results with other methods Some important challenges when dealing with grid generation and flow simulations in these complex geometries with variable multiphase flow patterns in alternate directions are discussed

9 citations


Cited by
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Journal ArticleDOI
TL;DR: The prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines, so the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored.
Abstract: Nasal delivery is the logical choice for topical treatment of local diseases in the nose and paranasal sinuses such as allergic and non-allergic rhinitis and sinusitis. The nose is also considered an attractive route for needle-free vaccination and for systemic drug delivery, especially when rapid absorption and effect are desired. In addition, nasal delivery may help address issues related to poor bioavailability, slow absorption, drug degradation, and adverse events in the gastrointestinal tract and avoids the first-pass metabolism in the liver. However, when considering nasal delivery devices and mechanisms, it is important to keep in mind that the prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines. The narrow nasal valve and the complex convoluted nasal geometry with its dynamic cyclic physiological changes provide efficient filtration and conditioning of the inspired air, enhance olfaction, and optimize gas exchange and fluid retention during exhalation. However, the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored. With this background, the advantages and limitations of existing and emerging nasal delivery devices and dispersion technologies are reviewed with focus on their clinical performance. The role and limitations of the in vitro testing in the FDA guidance for nasal spray pumps and pressurized aerosols (pressurized metered-dose inhalers) with local action are discussed. Moreover, the predictive value and clinical utility of nasal cast studies and computer simulations of nasal airflow and deposition with computer fluid dynamics software are briefly discussed. New and emerging delivery technologies and devices with emphasis on Bi-Directional™ delivery, a novel concept for nasal delivery that can be adapted to a variety of dispersion technologies, are described in more depth.

400 citations

01 Jan 2005
TL;DR: This paper describes how OptiNose is using Computational Fluid Dynamics (CFD) during the development process for their drug delivery concept and presents some comparison of the CFD computation results against physical experiments.
Abstract: Nasal delivery is considered for an increasing number of existing and new drugs and vaccines, but current nasal delivery devices have major disadvantages. The Norwegian company OptiNose AS is developing a novel concept that challenges traditional delivery systems. The patended bi-directional delivery system improves drug and vaccine distribution to the nasal mucous membrane while at the same time preventing lung deposition. It takes advantage of the posterior connection between the nasal passages persisting when the velum automatically closes during oral exhalation. It is the exhalation into the delivery device that triggers the release of particles into an airflow, which enters one nostril via a sealing nozzle and exits through the other nostril. This paper describes how OptiNose is using Computational Fluid Dynamics (CFD) during the development process for their drug delivery concept. The simulations are used to visualize and demonstrate the basic features of the bi-directional technique and discuss how its design and function could be further optimized. CFD computations thus increase the efficiency of device development and reduce the need for expensive and time consuming laboratory experiments. To perform successful CFD calculations on the nose, construction of a proper surface grid of the nasal cavity is important. The process of building the surface grid is presented in the paper. The final surface grid was next imported into Tgrid, a volume grid generator, and finally the simulations were carried out by use of the commercial CFD code FLUENT. These steps are described in the paper. Testing of the cell quality, both during surface grid and volume grid generation, is mandatory. The testing procedures are briefly presented in the paper. Finally, to be able to rely on the CFD computations done, one needs thorough validation. This article presents some comparison of the CFD computation results against physical experiments. The comparison analysis shows promising results.

32 citations

Journal ArticleDOI
TL;DR: A closer look at the current research trends as well as the future directions of aerosol-particle deposition with a high accuracy relative to experimental data is taken.
Abstract: The measurement of deposited aerosol particles in the respiratory tract via in vivo and in vitro approaches is difficult due to those approaches’ many limitations. In order to overcome these obstacles, different computational models have been developed to predict the deposition of aerosol particles inside the lung. Recently, some remarkable models have been developed based on conventional semi-empirical models, one-dimensional whole-lung models, three-dimensional computational fluid dynamics models, and artificial neural networks for the prediction of aerosol-particle deposition with a high accuracy relative to experimental data. However, these models still have some disadvantages that should be overcome shortly. In this paper, we take a closer look at the current research trends as well as the future directions of this research area.

27 citations

Journal ArticleDOI
TL;DR: Significant differences between unstructured mesh and hybrid mesh are determined highlighting the usefulness of hybrid mesh for nasal airflow studies.
Abstract: The accuracy of the numerical result is closely related to mesh density as well as its distribution. Mesh plays a very significant role in the outcome of numerical simulation. Many nasal airflow studies have employed unstructured mesh and more recently hybrid mesh scheme has been utilized considering the complexity of anatomical architecture. The objective of this study is to compare the results of hybrid mesh with unstructured mesh and study its effect on the flow parameters inside the nasal cavity. A three-dimensional nasal cavity model is reconstructed based on computed tomographic images of a healthy Malaysian adult nose. Navier-Stokes equation for steady airflow is solved numerically to examine inspiratory nasal flow. The pressure drop obtained using the unstructured computational grid is about 22.6 Pa for a flow rate of 20 L/min, whereas the hybrid mesh resulted in 17.8 Pa for the same flow rate. The maximum velocity obtained at the nasal valve using unstructured grid is 4.18 m/s and that with hybrid mesh is around 4.76 m/s. Hybrid mesh reported lower grid convergence index (GCI) than the unstructured mesh. Significant differences between unstructured mesh and hybrid mesh are determined highlighting the usefulness of hybrid mesh for nasal airflow studies.

20 citations

Journal ArticleDOI
TL;DR: Models of sinonasal cavities were created from postoperative magnetic resonance imaging scans in four patients, three of whom underwent a comprehensive FESS, the other a modified endoscopic Lothrop procedure to ascertain a multi-level approach to optimizing drug delivery in the sinuses.

17 citations