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

J Aerosol Med Pulm Drug Deliv. 2015 Dec;28(6):498-506. doi: 10.1089/jamp.2015.1225. Epub 2015 Sep 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Androstadienes / administration & dosage
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzyl Alcohols / administration & dosage
  • Bronchodilator Agents / administration & dosage*
  • Chlorobenzenes / administration & dosage
  • Clinical Trials as Topic
  • Drug Combinations
  • Drug Delivery Systems / instrumentation*
  • Dry Powder Inhalers*
  • Equipment Design
  • Humans
  • Inhalation*
  • Lung / physiopathology
  • Models, Anatomic
  • Models, Biological
  • Powders
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Quinuclidines / administration & dosage
  • Severity of Illness Index

Substances

  • Aerosols
  • Androstadienes
  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • Drug Combinations
  • GSK573719
  • Powders
  • Quinuclidines
  • vilanterol
  • fluticasone furoate

Associated data

  • ClinicalTrials.gov/NCT01345266
  • ClinicalTrials.gov/NCT02076269