title: Aerosol Drug Delivery During Noninvasive Positive Pressure Ventilation: Effects of Intersubject Variability and Excipient Enhanced Growth.
abstract: BACKGROUND
  Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV.
  
  
  METHODS
  A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered.
  
  
  RESULTS
  Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%-134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%-17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%-90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit.
  
  
  CONCLUSIONS
  The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration.
authors.affiliation: 1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Walenga
authors.affiliation: 1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University , Richmond, Virginia.|2 Department of Pharmaceutics, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.affiliation: 2 Department of Pharmaceutics, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Anubhav
authors.initials: A
authors.lastname: Kaviratna
authors.affiliation: 2 Department of Pharmaceutics, Virginia Commonwealth University , Richmond, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000328:Adult; D000336:Aerosols; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D008168:Lung / Q000378:metabolism*; D008397:Masks; D008953:Models, Anatomic; D009296:Nasal Cavity / Q000033:anatomy & histology; D009330:Nebulizers and Vaporizers; D063087:Noninvasive Ventilation / Q000379:methods; D011175:Positive-Pressure Respiration; D055815:Young Adult
chemical_list: D000336:Aerosols; D005079:Excipients
keywords: computational fluid dynamics; excipient enhanced growth; inline dry powder inhaler; nebulized aerosol; noninvasive positive pressure ventilation