title: Intermittent aerosol delivery to the lungs during high-flow nasal cannula therapy.
abstract: BACKGROUND
  Use of submicrometer particles combined with condensational growth techniques has been proposed to reduce drug losses within components of high-flow nasal cannula therapy systems and to enhance the dose reaching the lower respiratory tract. These methods have been evaluated using continuous inhalation flow rather than realistic inhalation/exhalation breathing cycles. The goal of this study was to evaluate in vitro aerosol drug delivery using condensational growth techniques during high-flow nasal cannula therapy using realistic breathing profiles and incorporating intermittent aerosol delivery techniques.
  
  
  METHODS
  A mixer-heater combined with a vibrating mesh nebulizer was used to generate a submicrometer aerosol using a formulation of 0.2% albuterol sulfate and 0.2% sodium chloride in water. Delivery efficiency of the aerosol for 1 min through a nasal cannula was considered using an intermittent delivery regime with aerosol being emitted for either the entire inhalation time (2 s) or half of the inhalation period (1 s) and compared with continuous delivery. The deposition of the aerosol was evaluated in the nasal delivery components (ventilator tubing and cannula) and an in vitro adult nose-mouth-throat (NMT) model using 3 realistic breathing profiles.
  
  
  RESULTS
  Significant improvements in dose delivered to the exit of the NMT model (ex-NMT) were observed for both condensational growth methods using intermittent aerosol delivery compared with continuous delivery, and increasing the tidal volume was found useful. The combination of the largest tidal volume with the shortest intermittent delivery time resulted in the lowest respiration losses and the highest ex-NMT delivered dose.
  
  
  CONCLUSIONS
  Intermittent aerosol delivery using realistic breathing profiles of submicrometer condensational growth aerosols was found to be efficient in delivering nasally administered drugs in an in vitro airway model.
authors.affiliation: Department of Pharmaceutics.
authors.forename: Laleh
authors.initials: L
authors.lastname: Golshahi
authors.affiliation: Department of Pharmaceutics Department of Mechanical and Nuclear Engineering.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.affiliation: Department of Pharmaceutics.
authors.forename: Mandana
authors.initials: M
authors.lastname: Azimi
authors.affiliation: Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Aamer
authors.initials: A
authors.lastname: Syed
authors.affiliation: Department of Pharmaceutics mhindle@vcu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010316:Particle Size
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D000420:Albuterol
keywords: condensational growth; high-flow nasal cannula therapy; in vitro airway model; nasal cannula; pulmonary drug delivery; submicrometer aerosol