title: Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler.
abstract: OBJECTIVE
  Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy.
  
  
  METHODS
  The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region.
  
  
  RESULTS
  The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%.
  
  
  CONCLUSIONS
  The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.
authors.affiliation: 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.|2Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: P Worth
authors.initials: PW
authors.lastname: Longest
authors.affiliation: 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Laleh
authors.initials: L
authors.lastname: Golshahi
authors.affiliation: 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.|2Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Srinivas R B
authors.initials: SR
authors.lastname: Behara
authors.affiliation: 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.affiliation: 1Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Dale R
authors.initials: DR
authors.lastname: Farkas
authors.affiliation: 2Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Hindle
mesh_terms: D000281:Administration, Intranasal; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002404:Catheterization / Q000295:instrumentation; D057785:Catheters; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000737:chemistry; D003198:Computer Simulation; D058995:Dry Powder Inhalers; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000033:anatomy & histology*; D008953:Models, Anatomic; D063087:Noninvasive Ventilation / Q000295:instrumentation; D009666:Nose / Q000033:anatomy & histology*; D010316:Particle Size; D011208:Powders; D017155:Wettability
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D005079:Excipients; D011208:Powders; D002939:Ciprofloxacin
keywords: active dry powder inhaler (DPI) system; enhanced condensational growth (ECG); excipient enhanced growth (EEG); high flow nasal cannula (HFNC); noninvasive ventilation (NIV)