title: In Vitro Dosing Performance of the ELLIPTA® Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™).
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.
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: Melanie
authors.initials: M
authors.lastname: Hamilton
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: Richard
authors.initials: R
authors.lastname: Leggett
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: Cheng
authors.initials: C
authors.lastname: Pang
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: Stephen
authors.initials: S
authors.lastname: Charles
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: Ben
authors.initials: B
authors.lastname: Gillett
authors.affiliation: GSK Research and Development Ltd , Ware, Hertfordshire, United Kingdom .
authors.forename: David
authors.initials: D
authors.lastname: Prime
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000730:Androstadienes / Q000008:administration & dosage; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001592:Benzyl Alcohols / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002722:Chlorobenzenes / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D006801:Humans; D001239:Inhalation; D008168:Lung / Q000503:physiopathology; D008953:Models, Anatomic; D008954:Models, Biological; D011208:Powders; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011812:Quinuclidines / Q000008:administration & dosage; D012720:Severity of Illness Index
chemical_list: D000336:Aerosols; D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D011208:Powders; D011812:Quinuclidines; C550468:vilanterol; C523187:fluticasone furoate
keywords: COPD; asthma; delivered dose; dry powder inhaler; electronic lung; fine particle dose; inhalation profiles