title: Influence of realistic inspiratory flow profiles on fine particle fractions of dry powder aerosol formulations.
abstract: OBJECTIVE
  The purpose of the study was to determine how air flow profiles affect fine particle fractions (FPF) (<5 microm) from dry powder aerosol formulations and whether laser diffraction (LD) could be used to measure FPF of aerosols generated by variable flows.
  
  
  METHODS
  Carrier-based formulations containing 1.5% w/w micronized salbutamol base blended with the 63-90 microm fraction of alpha-lactose monohydrate or sorbitol or maltose were aerosolised from a model glass device using either a constant flow rate or a predetermined flow profile. The FPFs of the same aerosolised particles were first measured by LD and then by a liquid impinger. Volunteer inhalation airflow profiles and 3-phase (acceleration, constant flow rate and deceleration) square wave airflow profiles were generated using the Electronic Lung and an Inhalation Profile Recorder. Similar experiments were conducted for a carrier-free formulation from the Bricanyl Turbohaler.
  
  
  RESULTS
  Salbutamol FPFs of all carrier-based formulations were found to increase by increasing the initial flow increase rate (FIR) from 200 to 600 l min(-1) s(-1) although they could be placed in an increasing order of maltose blend < sorbitol blend < lactose blend. A significant linear correlation was found between FPFs measured by LD and by inertial impaction (R (2) = 0.95, p < 0.01, ANOVA). For the Bricanyl Turbohaler, increasing FIR from 120 to 600 l min(-1) s(-1) for a constant peak flow rate (PFR) of 60 l min(-1) increased the mean Terbutaline FPF from 18.2% to 45.5%. For the volunteer inhalation profiles, a higher FIR tended to be associated with higher PFR, leading to a marked increase in drug FPF due to the combined effect of FIR and PFR.
  
  
  CONCLUSIONS
  Drug FPF from either carrier-free or carrier-based formulations is determined by both FIR and PFR. LD is a viable technique to measure the performance of dry powder aerosol formulations at realistic inspiratory flow profiles.
authors.affiliation: Pharmaceutical Science Research Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. gary.martin@kcl.ac.uk
authors.forename: Gary P
authors.initials: GP
authors.lastname: Martin
authors.forename: Christopher
authors.initials: C
authors.lastname: Marriott
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Zeng
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004337:Drug Carriers; D006801:Humans; D007785:Lactose; D007834:Lasers; D008320:Maltose; D008953:Models, Anatomic; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013012:Sorbitol; D013726:Terbutaline / Q000008:administration & dosage
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D011208:Powders; D013012:Sorbitol; D008320:Maltose; D007785:Lactose; D013726:Terbutaline; D000420:Albuterol