Gamma scintigraphic pulmonary deposition study of glycopyrronium/formoterol metered dose inhaler formulated using co-suspension delivery technology
File(s)
Author(s)
Type
Journal Article
Abstract
This gamma scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two actuations of GFF pMDI (7.2/5.0 μg per actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with 99mTc, up to 5 MBq per actuation. Gamma scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤ 0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.
Date Issued
2017-10-18
Date Acceptance
2017-10-18
Citation
European Journal of Pharmaceutical Sciences, 2017, 111, pp.450-457
ISSN
0928-0987
Publisher
Elsevier
Start Page
450
End Page
457
Journal / Book Title
European Journal of Pharmaceutical Sciences
Volume
111
Copyright Statement
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Co-suspension delivery technology
Gamma scintigraphy
Glycopyrronium
Formoterol fumarate dihydrate
Metered dose inhaler
Pulmonary deposition
LUNG DEPOSITION
AEROSOL DEPOSITION
SMALL AIRWAYS
VOLUNTEERS
MULTIPLE
EFFICACY
THERAPY
DISEASE
SYSTEM
ASTHMA
Publication Status
Accepted