title: Targeting aerosol deposition to and within the lung airways using excipient enhanced growth.
abstract: BACKGROUND
  Previous studies have characterized the size increase of combination submicrometer particles composed of a drug and hygroscopic excipient when exposed to typical airway thermodynamic conditions. The objective of this study was to determine the deposition and size increase characteristics of excipient enhanced growth (EEG) aerosols throughout the tracheobronchial (TB) airways and to evaluate the potential for targeted delivery.
  
  
  METHODS
  Submicrometer particles composed of a poorly water-soluble drug (insulin) and hygroscopic excipient (sodium chloride) were considered at drug:excipient mass ratios of 50:50 and 25:75. A previously validated computational fluid dynamics model was used to predict aerosol size increase and deposition in characteristic geometries of the mouth-throat (MT), upper TB airways through the third bifurcation (B3), and remaining TB airways through B15. Additional validation experiments were also performed for albuterol sulfate:mannitol particles. Both growth of combination particles and deposition are reported throughout the conducting airways for characteristic slow and deep (SD) and quick and deep (QD) inhalations.
  
  
  RESULTS
  For all EEG cases considered, MT deposition was less than 1% of the drug dose, which is at least one order of magnitude lower than with state-of-the-art and conventional inhalers. Final aerosol sizes exiting the TB region and entering the alveolar airways were all greater than 3 μm. For SD inhalation, deposition fractions of 20% were achieved in the lower TB region of B8-B15, which is a factor of 20-30×higher than conventional delivery devices. With QD inhalation, maximum alveolar delivery of 90% was observed.
  
  
  CONCLUSIONS
  Increasing the dose delivered to the lower TB region by a factor of 20-30×or achieving 90% delivery to the alveolar airways was considered effective aerosol targeting compared with conventional devices. The trend of higher flow rates resulting in better alveolar delivery of aerosols is unique to EEG and may be used to design highly efficient dry powder inhalers.
authors.affiliation: 1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University , Richmond, VA 23284.
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D057446:Hydrodynamics; D058427:Hygroscopic Agents / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008353:Mannitol / Q000737:chemistry; D008962:Models, Theoretical; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D012137:Respiratory System / Q000378:metabolism; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013816:Thermodynamics; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D005079:Excipients; D058427:Hygroscopic Agents; D007328:Insulin; D008353:Mannitol; D012965:Sodium Chloride; D000420:Albuterol