title: Inhalation of tobramycin using simulated cystic fibrosis patient profiles.
abstract: TOBI®Podhaler™ is a capsule-based drug-device combination (tobramycin inhalation powder [TIP] 28 mg capsules via unit-dose dry powder T-326 Inhaler [Podhaler™]) developed for treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF). We explored how inspiratory flow profiles and mouth-throat geometries affect drug delivery with the T-326 Inhaler.
  
  
  
  Inspiratory flow profiles were recorded from 38 subjects aged 6-71 who had CF and varying degrees of lung function impairment. Ten of the inspiratory flow profiles were simulated in the laboratory using a custom breath simulator to determine delivered dose (DD) from the T-326 Inhaler. In vitro total lung dose (TLDin vitro) was measured using four anatomical throat models, ranging from a child to a large adult.
  
  
  
  Aerosol performance was assessed across a range of inspiratory flow profiles. Mean DD ranged from 88.8% to 97.0% of declared capsule content. TLDin vitroranged from 54.8% to 72.4% of capsule content between the flow profile/throat options tested, and the mean TLDin vitroacross the range of flow profiles and anatomical throats tested was 63 ± 5%.
  
  
  
  Our findings indicate that the T-326 Inhaler provides reliable drug delivery at flow rates likely to be achieved by a broad spectrum of patients with CF. Importantly, forceful inhalation was not required to achieve a robust TLDin vitro. Pediatr Pulmonol. 2016;51:1159-1167. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, California.
authors.forename: Alfred
authors.initials: A
authors.lastname: Haynes
authors.affiliation: Florida State University College of Medicine, Orlando, Florida.
authors.forename: David
authors.initials: D
authors.lastname: Geller
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, California. jeff.weers@novartis.com.
authors.forename: Jeffry
authors.initials: J
authors.lastname: Weers
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, California.
authors.forename: Brian
authors.initials: B
authors.lastname: Ament
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Richard
authors.initials: R
authors.lastname: Pavkov
authors.affiliation: Novartis Pharmaceuticals Corporation, San Carlos, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Malcolmson
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Laurie
authors.initials: L
authors.lastname: Debonnett
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Paul
authors.initials: P
authors.lastname: Mastoridis
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Anthony
authors.initials: A
authors.lastname: Yadao
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Heuerding
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000503:physiopathology; D058995:Dry Powder Inhalers; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D010614:Pharynx; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin
keywords: PulmoSphere; T-326 Inhaler; delivered dose; dry powder inhaler; inspiratory flow