title: The acoustic features of inhalation can be used to quantify aerosol delivery from a Diskus™ dry powder inhaler.
abstract: OBJECTIVE
  Some patients are unable to generate the peak inspiratory flow rate (PIFR) necessary to de-agglomerate drug particles from dry powder inhalers (DPIs). In this study we tested the hypothesis that the acoustic parameters of an inhalation are related to the PIFR and hence reflect drug delivery.
  
  
  METHODS
  A sensitivity analysis of the relationship of the acoustics of inhalation to simultaneously recorded airflow, in a cohort of volunteers (n = 92) was performed. The Next Generation Impactor (NGI) was used to assess in vitro drug delivery from salmeterol/fluticasone and salbutamol Diskus™ DPIs. Fine particle fraction, FPF, (<5 μm) was measured at 30-90 l/min for 2-6 s and correlated with acoustically determined flow rate (IFRc). In pharmacokinetic studies using a salbutamol (200 μg) Diskus™, volunteers inhaled either at maximal or minimal effort on separate days.
  
  
  RESULTS
  PIFRc was correlated with spirometrically determined values (R (2) = 0.88). In in vitro studies, FPF increased as both flow rate and inhalation duration increased for the salmeterol/fluticasone Diskus™ (Adjusted R (2) = 0.95) and was proportional to flow rate only for the salbutamol Diskus™ (Adjusted R (2) = 0.71). In pharmacokinetic studies, blood salbutamol levels measured at 20 min were significantly lower when PIFRc was less than 60 l/min, p < 0.0001.
  
  
  CONCLUSIONS
  Acoustically-determined PIFR is a suitable method for estimating drug delivery and for monitoring inhalation technique over time.
authors.affiliation: Department of Medicine Respiratory Research Division, Royal College of Surgeons in Ireland, Dublin, Ireland, jansenseheult@rcsi.ie.
authors.forename: Jansen N
authors.initials: JN
authors.lastname: Seheult
authors.forename: Peter
authors.initials: P
authors.lastname: O'Connell
authors.forename: Kee Chun
authors.initials: KC
authors.lastname: Tee
authors.forename: Tariq
authors.initials: T
authors.lastname: Bholah
authors.forename: Hasan
authors.initials: H
authors.lastname: Al Bannai
authors.forename: Imran
authors.initials: I
authors.lastname: Sulaiman
authors.forename: Elaine
authors.initials: E
authors.lastname: MacHale
authors.forename: Shona
authors.initials: S
authors.lastname: D'Arcy
authors.forename: Martin S
authors.initials: MS
authors.lastname: Holmes
authors.forename: David
authors.initials: D
authors.lastname: Bergin
authors.forename: Emer
authors.initials: E
authors.lastname: Reeves
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.forename: Gloria
authors.initials: G
authors.lastname: Crispino-O'Connell
authors.forename: Carsten
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
mesh_terms: D000162:Acoustics / Q000295:instrumentation*; D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D000730:Androstadienes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D058995:Dry Powder Inhalers; D004867:Equipment Design; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D001239:Inhalation / Q000502:physiology*; D007320:Inspiratory Capacity / Q000502:physiology*
chemical_list: D000336:Aerosols; D000730:Androstadienes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol