Biophysical model to predict lung delivery from a dual bronchodilator dry-powder inhaler
Author(s)
Dolovich, Myrna B
Kuttler, Andreas
Dimke, Thomas J
Usmani, Omar S
Type
Journal Article
Abstract
A biophysical lung model was designed to predict inhaled drug deposition in patients with obstructive airway disease, and quantitatively investigate sources of deposition variability. Different mouth-throat anatomies at varying simulated inhalation flows were used to calculate the lung dose of indacaterol/glycopyrronium [IND/GLY] 110/50 µg (QVA149) from the dry-powder inhaler Breezhaler®. Sources of variability in lung dose were studied using computational fluid dynamics, supported by aerosol particle sizing measurements, particle image velocimetry and computed tomography. Anatomical differences in mouth-throat geometries were identified as a major source of inter-subject variability in lung deposition. Lung dose was similar across inhalation flows of 30–120 L/min with a slight drop in calculated delivery at high inspiratory flows. Delivery was relatively unaffected by inhaler inclination angle. The delivered lung dose of the fixed-dose combination IND/GLY matched well with corresponding monotherapy doses. This biophysical model indicates low extra-thoracic drug loss and consistent lung delivery of IND/GLY, independent of inhalation flows. This is an important finding for patients across various ages and lung disease severities. The model provides a quantitative, mechanistic simulation of inhaled therapies that could provide a test system for estimating drug delivery to the lung and complement traditional clinical studies.
Date Issued
2019-12-01
Date Acceptance
2019-05-27
Citation
International Journal of Pharmaceutics: X, 2019, 1, pp.1-9
ISSN
2590-1567
Publisher
Elsevier
Start Page
1
End Page
9
Journal / Book Title
International Journal of Pharmaceutics: X
Volume
1
Copyright Statement
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000538566300006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Inhaler devices
Lung deposition
Computational fluid dynamics
Chronic obstructive pulmonary disease
Dry powder inhaler
MOUTH-THROAT MODELS
IN-VITRO
AEROSOL DEPOSITION
DRUG-DELIVERY
FLOW
PERFORMANCE
BIOEQUIVALENCE
FLUTICASONE
COMBINATION
RESISTANCE
Publication Status
Published
Article Number
ARTN 100018
Date Publish Online
2019-05-30