AAPS PharmSciTech

, Volume 15, Issue 5, pp 1126–1137 | Cite as

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

  • Hlack Mohammed
  • Jan Arp
  • Frank Chambers
  • Mark Copley
  • Volker Glaab
  • Mark Hammond
  • Derek Solomon
  • Kerry Bradford
  • Theresa Russell
  • Yvonne Sizer
  • Steven C. Nichols
  • Daryl L. Roberts
  • Christopher Shelton
  • Roland Greguletz
  • Jolyon P. Mitchell
Research Article

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.

KEY WORDS

cascade impactor compendial method dry powder inhaler inhaler resistance sample volume 

Notes

ACKNOWLEDGMENTS

The authors wish to acknowledge the support of TEVA-Pharmachemie, Netherlands, and Boehringer-Ingelheim, Germany, for the supply of the DPI products and to other members of the Cascade Impactor Sub-Team of the EPAG for their advice and support during the experimental work and in the internal reviewing of this article.

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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Hlack Mohammed
    • 1
  • Jan Arp
    • 2
  • Frank Chambers
    • 3
  • Mark Copley
    • 4
  • Volker Glaab
    • 5
  • Mark Hammond
    • 6
  • Derek Solomon
    • 6
  • Kerry Bradford
    • 6
  • Theresa Russell
    • 6
  • Yvonne Sizer
    • 6
  • Steven C. Nichols
    • 7
  • Daryl L. Roberts
    • 8
  • Christopher Shelton
    • 9
  • Roland Greguletz
    • 10
  • Jolyon P. Mitchell
    • 11
  1. 1.GSK plcWareUK
  2. 2.TEVA-PharmachemieHaarlemNetherlands
  3. 3.CovanceHarrogateUK
  4. 4.Copley Scientific LtdNottinghamUK
  5. 5.Boehringer-Ingelheim Pharma GmbH & Co. KGIngelheimGermany
  6. 6.Intertek Pharmaceutical Services MelbournCambridgeshireUK
  7. 7.OINDP ConsultancyCheshireUK
  8. 8.MSP CorporationShoreviewUSA
  9. 9.Boehringer-Ingelheim Roxane IncColumbusUSA
  10. 10.Almirall-Sofotec GmbHBad HomburgGermany
  11. 11.Jolyon Mitchell Inhaler Consulting Services IncLondonCanada

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