Application of a One-Dimensional Computational Model for the Prediction of Deposition from a Dry Powder Inhaler

J Aerosol Med Pulm Drug Deliv. 2017 Dec;30(6):435-443. doi: 10.1089/jamp.2016.1363. Epub 2017 Jul 6.

Abstract

Background: Accurate prediction of the regional deposition of inhaled dry powders as a function of powder properties and breathing pattern is a long-term research goal for pulmonary drug delivery. In the present work, deposition along the respiratory tract of dry powders of Fluticasone propionate and Salmeterol is predicted.

Methods: A one-dimensional particle transport and deposition model is used, whose novelty is in the treatment of the alveolar space of each airway generation as an efficient mixing chamber. This assumption has been supported by simulations and measurements during the last 20 years. The model is applied to two popular pulmonary tree geometries, to investigate the effect of particle size on localized deposition and to estimate the uncertainty due to variations in airway size.

Results and conclusions: Application of the model for the specific particle size distribution measured by a cascade impactor in the marketed product ELPENhaler, predicts the whole lung deposition (WLD), as well as the split between pulmonary (PU) and tracheobronchial (TB) deposition. Introduction in the model of modified particle size distributions with increased fractions of fine particles, indicates that the fine-particle dose is a satisfactory predictor of WLD but not of the PU/TB ratio.

Keywords: Fluticasone propionate; Salmeterol; alveolar mixing; computational modeling; dry powder inhaler; particle deposition.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacokinetics
  • Computer Simulation*
  • Drug Delivery Systems*
  • Dry Powder Inhalers
  • Equipment Design
  • Fluticasone / administration & dosage*
  • Fluticasone / pharmacokinetics
  • Humans
  • Lung / metabolism
  • Particle Size
  • Salmeterol Xinafoate / administration & dosage*
  • Salmeterol Xinafoate / pharmacokinetics
  • Tissue Distribution
  • Uncertainty

Substances

  • Aerosols
  • Bronchodilator Agents
  • Salmeterol Xinafoate
  • Fluticasone