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In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler

BACKGROUND: Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and ther...

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Autores principales: Hamilton, Melanie, Anderson, Martin, Dhand, Rajiv, Patmore, Oonagh, Prime, David, Taylor, Edward
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942181/
https://www.ncbi.nlm.nih.gov/pubmed/36695722
http://dx.doi.org/10.1089/jamp.2021.0061
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author Hamilton, Melanie
Anderson, Martin
Dhand, Rajiv
Patmore, Oonagh
Prime, David
Taylor, Edward
author_facet Hamilton, Melanie
Anderson, Martin
Dhand, Rajiv
Patmore, Oonagh
Prime, David
Taylor, Edward
author_sort Hamilton, Melanie
collection PubMed
description BACKGROUND: Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. MATERIALS AND METHODS: The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. RESULTS: During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. CONCLUSIONS: Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.
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spelling pubmed-99421812023-02-22 In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler Hamilton, Melanie Anderson, Martin Dhand, Rajiv Patmore, Oonagh Prime, David Taylor, Edward J Aerosol Med Pulm Drug Deliv Research Articles BACKGROUND: Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. MATERIALS AND METHODS: The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. RESULTS: During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. CONCLUSIONS: Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF. Mary Ann Liebert, Inc., publishers 2023-02-01 2023-02-09 /pmc/articles/PMC9942181/ /pubmed/36695722 http://dx.doi.org/10.1089/jamp.2021.0061 Text en © Melanie Hamilton, et al., 2023. Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Articles
Hamilton, Melanie
Anderson, Martin
Dhand, Rajiv
Patmore, Oonagh
Prime, David
Taylor, Edward
In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title_full In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title_fullStr In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title_full_unstemmed In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title_short In Vitro Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler
title_sort in vitro drug delivery of a fixed-dose combination of fluticasone furoate/umeclidinium/vilanterol from a dry powder inhaler
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942181/
https://www.ncbi.nlm.nih.gov/pubmed/36695722
http://dx.doi.org/10.1089/jamp.2021.0061
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