In Vitro Measurement of Regional Nasal Drug Delivery with Flonase,® Flonase® Sensimist,™ and MAD Nasal™ in Anatomically Correct Nasal Airway Replicas of Pediatric and Adult Human Subjects

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.

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An in vitro evaluation of importance of airway anatomy in sub-regional nasal and paranasal drug delivery with nebulizers using three different anatomical nasal airway replicas of 2-, 5- and 50-Year old human subjects

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2019.04.019 ◽

2019 ◽

Vol 563 ◽

pp. 426-436 ◽

Cited By ~ 4

Author(s):

Sana Hosseini ◽

Laleh Golshahi

Keyword(s):

Drug Delivery ◽

Human Subjects ◽

Nasal Airway ◽

In Vitro Evaluation ◽

Airway Anatomy

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Real-time quantitative monitoring of in vitro nasal drug delivery by a nasal epithelial mucosa-on-a-chip model

Expert Opinion on Drug Delivery ◽

10.1080/17425247.2021.1873274 ◽

2021 ◽

Author(s):

Hanieh Gholizadeh ◽

Hui Xin Ong ◽

Peta Bradbury ◽

Agisilaos Kourmatzis ◽

Daniela Traini ◽

...

Keyword(s):

Drug Delivery ◽

Real Time ◽

Nasal Drug Delivery ◽

Quantitative Monitoring

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Nasal drug delivery: An in vitro characterization of transepithelial electrical properties and fluxes in the presence or absence of enhancers

Journal of Controlled Release ◽

10.1016/0168-3659(88)90043-0 ◽

1988 ◽

Vol 8 (2) ◽

pp. 167-177 ◽

Cited By ~ 44

Author(s):

M.A. Wheatley ◽

J. Dent ◽

E.B. Wheeldon ◽

P.L. Smith

Keyword(s):

Drug Delivery ◽

Electrical Properties ◽

Nasal Drug Delivery ◽

In Vitro Characterization

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Role of nasal casts for in vitro evaluation of nasal drug delivery and quantitative evaluation of various nasal casts

Therapeutic Delivery ◽

10.4155/tde-2020-0054 ◽

2020 ◽

Vol 11 (8) ◽

pp. 485-495

Author(s):

Per G Djupesland ◽

John C Messina ◽

Ramy A Mahmoud

Keyword(s):

Computed Tomography ◽

Drug Delivery ◽

Quantitative Evaluation ◽

Healthy Male ◽

Nasal Drug Delivery ◽

Normal Range ◽

Cross Sectional ◽

Drug Deposition

Background: Nasal casts may characterize intranasal drug deposition. Methodology: The Koken cast, described as ‘anatomically correct’, and the Optinose cast, derived from MRI of a healthy male during velum closure, were dimensionally compared and assessed for deposition assessment suitability. Results: Smallest vertical cross-sectional areas (valve region) for Koken and Optinose right/left: 2.55/2.75 and 1.18/1.18 cm2, respectively, versus a ‘normative’ mean (range) of 0.85 cm2 (0.2–1.6 cm2). Intranasal volumes differed (computed tomography/water fill): Koken, 35.8/38.6 cm3 and Optinose, 24.1/25.0 cm3, versus a ‘normative’ mean (range) of 26.4 cm3 (20.9–31.1 cm3). Conclusion: Koken cast dimensions are larger than the normal range and the Optinose cast. The validity of casts for regulatory drug deposition studies is suspect.

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Use of anatomically-accurate 3-dimensional nasal airway models of adult human subjects in a novel methodology to identify and evaluate the internal nasal valve

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2020.103896 ◽

2020 ◽

Vol 123 ◽

pp. 103896

Author(s):

Sana Hosseini ◽

Theodore A. Schuman ◽

Ross Walenga ◽

John V. Wilkins ◽

Andrew Babiskin ◽

...

Keyword(s):

Human Subjects ◽

Nasal Airway ◽

Nasal Valve ◽

3 Dimensional ◽

Adult Human

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Development of a nasal cast model to test medicinal nasal devices

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1243/09544119jeim423 ◽

2008 ◽

Vol 222 (7) ◽

pp. 1013-1022 ◽

Cited By ~ 9

Author(s):

R Hughes ◽

J Watterson ◽

C Dickens ◽

D Ward ◽

A Banaszek

Keyword(s):

Drug Delivery ◽

Nasal Cavity ◽

Method Development ◽

Test Apparatus ◽

Nasal Drug Delivery ◽

Nasal Airways ◽

Cast Model ◽

Manufacturing Technologies ◽

Drug Delivery Devices

Bespak, a division of Consort Medical plc, and Queen's University Belfast have developed a viable and unique in-vitro testing capability for nasal drug delivery devices. The aim was to evaluate and optimize current and conceptual drug delivery devices by quantifying the deposition of drug in the various distinct regions of the nasal cavity. The development of this test apparatus employed computed tomography (CT) scan data of the human nasal cavity to construct an accurate representation of the human nasal airways. An investigation of suitable materials and manufacturing technologies was required, together with extensive analytical method development. It is possible for this technique to be further developed in an attempt to create a standardized apparatus based on nasal geometry that can be used to compare accurately deposition from drug delivery devices. This paper presents the issues encountered in the development of this test apparatus, including manufacturing and material limitations, investigation and choice of suitable materials, laboratory testing considerations, and the steps required to validate the analytical process.

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