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2285072 
Journal Article 
Targeting Aerosol Deposition to and Within the Lung Airways Using Excipient Enhanced Growth 
Tian, G; Longest, PW; Li, X; Hindle, M 
2013 
Yes 
Journal of Aerosol Medicine and Pulmonary Drug Delivery
ISSN: 1941-2711
EISSN: 1941-2703 
26 
5 
248-265 
English 
23286828 
WOS:000324890900085 
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. 
respiratory drug delivery; excipient enhanced growth (EEG); nanoaerosols; hygroscopic droplet growth; engineered combination particles; stochastic individual path (SIP) airway modeling; computational fluid dynamics (CFD) simulations; in vitro aerosol experiments