title: Investigation of dry powder inhaler (DPI) resistance and aerosol dispersion timing on emitted aerosol aerodynamic particle sizing by multistage cascade impactor when sampled volume is reduced from compendial value of 4 L.
abstract: Compendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes. APSD measurements were made using the same CI systems with inhalers representing low and high flow resistance extremes (Cyclohaler® and HandiHaler® DPIs, respectively). The ratio of sample volume to internal dead space (normalized volume (V*)) was varied from 0.25 to 1.98 (NGI) and from 0.43 to 3.46 (ACI). Inhaler resistance was a contributing factor to the rate of bolus transfer; the higher resistance DPI completing bolus relocation to the NGI pre-separator via the inlet when V* was as small as 0.25, whereas only ca. 50% of the bolus mass was collected at this condition with the Cyclohaler® DPI. Size fractionation of the bolus from either DPI was completed within the ACI at smaller values of V* than within the NGI. Bolus transfer from the Cyclohaler® capsule and from the HandiHaler® to the ACI system were unaffected by the different flow rise time observed in the two different flow controller systems, and the effects the ACI-based on APSD measurements were marginal.
authors.affiliation: GSK plc, Park Road, Ware, Hertfordshire, SG12 0DP, UK.
authors.forename: Hlack
authors.initials: H
authors.lastname: Mohammed
authors.forename: Jan
authors.initials: J
authors.lastname: Arp
authors.forename: Frank
authors.initials: F
authors.lastname: Chambers
authors.forename: Mark
authors.initials: M
authors.lastname: Copley
authors.forename: Volker
authors.initials: V
authors.lastname: Glaab
authors.forename: Mark
authors.initials: M
authors.lastname: Hammond
authors.forename: Derek
authors.initials: D
authors.lastname: Solomon
authors.forename: Kerry
authors.initials: K
authors.lastname: Bradford
authors.forename: Theresa
authors.initials: T
authors.lastname: Russell
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sizer
authors.forename: Steven C
authors.initials: SC
authors.lastname: Nichols
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Roberts
authors.forename: Christopher
authors.initials: C
authors.lastname: Shelton
authors.forename: Roland
authors.initials: R
authors.lastname: Greguletz
authors.forename: Jolyon P
authors.initials: JP
authors.lastname: Mitchell
mesh_terms: D000336:Aerosols; D058995:Dry Powder Inhalers; D004867:Equipment Design; D010316:Particle Size
chemical_list: D000336:Aerosols