In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™)

Melanie Hamilton, Richard Leggett, Cheng Pang, Stephen Charles, Ben Gillett, David Prime, Melanie Hamilton, Richard Leggett, Cheng Pang, Stephen Charles, Ben Gillett, David Prime

Abstract

Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA(®) dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo.

Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast. A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler. Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only).

Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6-136.9 L/min), pressure drops (1.2-13.8 kPa), and inhaled volumes through the inhaler (0.7-4.2L). DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed. Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy.

Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy. Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency.

Trial registration: ClinicalTrials.gov NCT01345266 NCT02076269.

Keywords: COPD; asthma; delivered dose; dry powder inhaler; electronic lung; fine particle dose; inhalation profiles.

Figures

FIG. 1.
FIG. 1.
Flow rate versus time for each patient representative maximal effort inhalation profile replicated for the assessments of (a) FF/VIa, (b) FFb, (c) UMEC/VIa, and (d) UMECb. COPD, chronic obstructive pulmonary disease; FF, fluticasone furoate; PIFR, peak inspiratory flow rate; UMEC, umeclidinium; VI, vilanterol. aDelivered via the two-strip ELLIPTA inhaler. bDelivered via the single-strip ELLIPTA inhaler.
FIG. 2.
FIG. 2.
DD, ETD, and FPD (% nominal blister content) versus PIFR (L/min) for (a) FF delivered as a component of FF/VIa, (b) VI delivered as a component of FF/VIa, (c) UMEC delivered as a component of UMEC/VIa, (d) VI delivered as a component of UMEC/VIa, (e) FF 100 μg and 200 μgb, and (f) UMEC 62.5 μgb. DD, delivered dose; ETD, ex-throat dose; FF, fluticasone furoate; FPD, fine particle dose; PIFR, peak inspiratory flow rate; UMEC, umeclidinium; VI, vilanterol. aDelivered via the two-strip ELLIPTA inhaler. bDelivered via the single-strip ELLIPTA inhaler.

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Source: PubMed

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