In vitro dose comparison of Respimat ® inhaler with dry powder inhalers for COPD maintenance therapy

Int J Chron Obstruct Pulmon Dis. 2017 May 26;12:1565-1577. doi: 10.2147/COPD.S115886. eCollection 2017.

Abstract

Background: Combining in vitro mouth-throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD) simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD) treatment.

Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL) was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI). Idealized breathing patterns from COPD patient groups - moderate and very severe COPD - were applied. Theoretical lung deposition patterns were assessed by an individual path model.

Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5%) for the moderate COPD breathing pattern and 67% (SD 5%) for very severe COPD breathing pattern. The percentages refer to nominal dose (ND) in vitro. This is in the range of 44%-63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2%) for moderate disease simulation and 51% (SD 2%) for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2%) for moderate and 42% (SD 1%) for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3%) for moderate and 55% (SD 2%) for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3%) and 41% (SD 2%), respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that deposition occurs mainly in the small airways. In summary, Respimat showed the lowest amount of particles depositing in the mouth-throat model and the highest amount reaching all regions of the simulation lung model.

Keywords: CFD; NGI; Respimat; inhalation; lung deposition; throat model.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Androstadienes / administration & dosage
  • Benzyl Alcohols / administration & dosage
  • Bronchodilator Agents / administration & dosage*
  • Chlorobenzenes / administration & dosage
  • Computer Simulation
  • Drug Combinations
  • Dry Powder Inhalers*
  • Equipment Design
  • Glycopyrrolate / administration & dosage
  • Humans
  • Hydrodynamics
  • Lung / pathology
  • Lung / physiopathology*
  • Metered Dose Inhalers*
  • Models, Anatomic*
  • Muscarinic Antagonists / administration & dosage
  • Pharynx / anatomy & histology*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiration
  • Severity of Illness Index
  • Tiotropium Bromide / administration & dosage
  • Tropanes / administration & dosage

Substances

  • Androstadienes
  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • Drug Combinations
  • Muscarinic Antagonists
  • Tropanes
  • fluticasone furoate-vilanterol trifenatate
  • aclidinium bromide
  • Glycopyrrolate
  • Tiotropium Bromide