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.
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: Carolina Althoff Souza; Nestor L Müller; Julia Flint; Joanne L Wright; Andrew Churg Journal: AJR Am J Roentgenol Date: 2005-12 Impact factor: 3.959
Authors: K J Haley; M E Sunday; B R Wiggs; H P Kozakewich; J J Reilly; S J Mentzer; D J Sugarbaker; C M Doerschuk; J M Drazen Journal: Am J Respir Crit Care Med Date: 1998-08 Impact factor: 21.405
Authors: Benjamin M Spence; Worth Longest; Xiangyin Wei; Sneha Dhapare; Michael Hindle Journal: J Aerosol Med Pulm Drug Deliv Date: 2019-03-11 Impact factor: 2.849
Authors: Ross L Walenga; P Worth Longest; Anubhav Kaviratna; Michael Hindle Journal: J Aerosol Med Pulm Drug Deliv Date: 2017-01-11 Impact factor: 2.849
Authors: Guihong Chai; Amr Hassan; Tuo Meng; Lihua Lou; Jonathan Ma; Russell Simmers; Lei Zhou; Bruce K Rubin; Qi Tony Zhou; P Worth Longest; Michael Hindle; Qingguo Xu Journal: Nanomedicine Date: 2020-07-03 Impact factor: 5.307