title: Inhalation performance of physically mixed dry powders evaluated with a simple simulator for human inspiratory flow patterns.
abstract: OBJECTIVE
  To construct a simple simulator reproducing human inspiratory flow patterns and use it to evaluate the inhalation performance of active ingredient particle-carrier particle systems (physically mixed dry powders).
  
  
  METHODS
  Inspiratory flow patterns were collected and analyzed using a flow recorder. The simulator was constructed using an airtight container, a valve, and a connecting tube. Several of the patterns reproduced by the simulator were compared with those recorded. In addition, the influence of inspiratory flow on the inhalation performance of physically mixed dry powders composed of salbutamol sulfate (SS) and coarse lactose monohydrate was investigated using a twin-stage liquid impinger (TSLI) equipped with the simulator.
  
  
  RESULTS
  Human inspiratory flow patterns could be characterized by three parameters: inspiratory flow volume (area under the flow rate-time curve (AUC)), flow increase rate (FIR), and peak flow rate (PFR). The patterns could be reproduced using the simulator. Testing with the simulator in vitro revealed that PFR, but not FIR or AUC, greatly affected the inhalation performance of physically mixed dry powders.
  
  
  CONCLUSIONS
  The simulator is simple to construct and can schematically reproduce human inspiratory flow patterns. Testing with a TSLI and the simulator is useful to evaluate dry powder formulations for clinical application.
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Hira
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kito
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ishizeki
authors.forename: Toyoko
authors.initials: T
authors.lastname: Okada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D058995:Dry Powder Inhalers; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D011208:Powders; D013499:Surface Properties
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D011208:Powders; D007785:Lactose; D000420:Albuterol