title: Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler(®) in Comparison with Diskus(®) and Turbohaler(®) Dry Powder Inhalers.
abstract: BACKGROUND
  European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler(®) (beclomethasone dipropionate/formoterol fumarate), Seretide(®) Diskus(®) (fluticasone propionate/salmeterol xinafoate), and Symbicort(®) Turbohaler(®) (budesonide/formoterol fumarate).
  
  
  METHODS
  The delivered dose uniformity was tested using a dose unit sampling apparatus (DUSA) at inhalation volumes either 2.0 or 4.0 L and flow rates 30, 40, 60, or 90 L/min. The aerodynamic assessment was carried out using a Next Generation Impactor by discharging each inhaler at 30, 40, 60, or 90 L/min for a time sufficient to obtain an air volume of 4 L.
  
  
  RESULTS
  Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) showed a consistent dose delivery for both the drugs included in the formulation, independently of the applied flow rate. Contrary, Symbicort(®) Turbohaler(®) showed a high decrease of the emitted dose for both budesonide and formoterol fumarate when the device was operated at airflow rate lower that 60 L/min. The aerosolizing performance of NEXThaler(®) and Diskus(®) was unaffected by the flow rate applied. Turbohaler(®) proved to be the inhaler most sensitive to changes in flow rate in terms of fine particle fraction (FPF) for both components. Among the combinations tested, Foster NEXThaler(®) was the only one capable to deliver around 50% of extra-fine particles relative to delivered dose.
  
  
  CONCLUSIONS
  NEXThaler(®) and Diskus(®) were substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass.
authors.affiliation: 1 Department of Pharmacy, University of Parma , Parma, Italy .|2 Institute of Pharmaceutical Science, King's College London , London, United Kingdom .
authors.forename: Francesca
authors.initials: F
authors.lastname: Buttini
authors.affiliation: 3 Chiesi Farmaceutici SpA , Parma, Italy .
authors.forename: Gaetano
authors.initials: G
authors.lastname: Brambilla
authors.affiliation: 3 Chiesi Farmaceutici SpA , Parma, Italy .
authors.forename: Diego
authors.initials: D
authors.lastname: Copelli
authors.affiliation: 3 Chiesi Farmaceutici SpA , Parma, Italy .
authors.forename: Viviana
authors.initials: V
authors.lastname: Sisti
authors.affiliation: 4 Interdepartmental Center, Biopharmanet-TEC, University of Parma , Parma, Italy .
authors.forename: Anna Giulia
authors.initials: AG
authors.lastname: Balducci
authors.affiliation: 1 Department of Pharmacy, University of Parma , Parma, Italy .
authors.forename: Ruggero
authors.initials: R
authors.lastname: Bettini
authors.affiliation: 3 Chiesi Farmaceutici SpA , Parma, Italy .
authors.forename: Irene
authors.initials: I
authors.lastname: Pasquali
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001507:Beclomethasone / Q000008:administration & dosage; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D000069502:Budesonide, Formoterol Fumarate Drug Combination / Q000008:administration & dosage; D058995:Dry Powder Inhalers; D004867:Equipment Design; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage; D000068759:Formoterol Fumarate / Q000008:administration & dosage; D005938:Glucocorticoids / Q000008:administration & dosage*; D008422:Materials Testing; D010316:Particle Size; D011208:Powders; D011312:Pressure; D013997:Time Factors
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D011208:Powders; D001507:Beclomethasone; D000068759:Formoterol Fumarate
keywords: Diskus®; NEXThaler®; NGI flow rate; Turbohaler®; aerodynamic assessment; extra-fine particle mass