Pulmonary deposition of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler formulated using co-suspension delivery technology in healthy male subjects.

Autor: Israel S; Simbec Research Ltd, Merthyr Tydfil, South Wales, CF48 4DR, UK., Kumar A; Kelly Services Global LLC, Suite 401A, 999W. Big Beaver Rd., Troy, MI, 48084, USA., DeAngelis K; Formerly of AstraZeneca, 4222 Emperor Blvd, Suite 560, Durham, NC, 27703, USA., Aurivillius M; AstraZeneca Gothenburg, Pepparedsleden 1, SE-431 50, Mölndal, Sweden., Dorinsky P; AstraZeneca, 4222 Emperor Blvd, Suite 560, Durham, NC, 27703, USA. Electronic address: paul.dorinsky1@astrazeneca.com., Roche N; Respiratory Medicine, Hôpital Cochin (AP-HP), University Paris Descartes, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France., Usmani OS; National Heart and Lung Institute (NHLI), Imperial College London & Royal Brompton Hospital, Guy Scadding Building, Dovehouse St, Chelsea, London SW3 6LY, UK.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2020 Oct 01; Vol. 153, pp. 105472. Date of Electronic Publication: 2020 Jul 16.
DOI: 10.1016/j.ejps.2020.105472
Abstrakt: This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 μg per actuation) radiolabelled with 99m Tc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
Competing Interests: Declaration of Competing Interest Samuel Israel has no conflicts to report. Ashish Kumar is an employee of Kelly Services Global LLC. Nicolas Roche reports grants and personal fees from Boehringer Ingelheim, Novartis, Pfizer and personal fees from AstraZeneca, Chiesi, Cipla, GlaxoSmithKline, Mundipharma, Sanofi, Sandoz, Teva, Trudell, Zambon and 3 M. Omar S. Usmani reports academic grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and personal fees from Aerocrine, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Mundipharma, NAPP, Prosonix, Sandoz, Takeda and Zentiva. Magnus Aurivillius and Paul Dorinsky are employees of AstraZeneca. Kiernan DeAngelis is a former employee of AstraZeneca.
(Copyright © 2020 AstraZeneca. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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