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Good Cascade Impactor Practice (GCIP) and Considerations for “In-Use” Specifications

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Abstract

The multi-stage cascade impactor (CI) is widely used to determine aerodynamic particle size distributions (APSDs) of orally inhaled products. Its size-fractionating capability depends primarily on the size of nozzles of each stage. Good Cascade Impactor Practice (GCIP) requires that these critical dimensions are linked to the accuracy of the APSD measurement based on the aerodynamic diameter size scale. Effective diameter (D eff) is the critical dimension describing any nozzle array, as it is directly related to stage cut-point size (d 50). d 50 can in turn be determined by calibration using particles of known aerodynamic diameter, providing traceability to the international length standard. Movements in D eff within manufacturer tolerances for compendial CIs result in the worst case in shifts in d 50 of <±10%. Stage mensuration therefore provides satisfactory control of measurement accuracy. The accurate relationship of D eff to d 50 requires the CI system to be leak-free, which can be checked by sealing the apparatus at the entry to the induction port and isolating it from the vacuum source and measuring the rate of pressure rise before each use. Mensuration takes place on an infrequent basis compared with the typical interval between individual APSD determinations. Measurement of stage flow resistance (pressure drop; ΔP stage) could enable the user to know that the CI stages are fit for use before every APSD measurement, by yielding an accurate measure of D eff. However, more data are needed to assess the effects of wear and blockage before this approach can be advocated as part of GCIP.

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Acknowledgments

The authors wish to acknowledge the support received through members of the Impactor Sub-Team of the European Pharmaceutical Aerosol Group (EPAG) during discussions related to the topics covered by this article. They also wish to acknowledge Copley Scientific, and Westech Instrument Services, for the supply of data and other information from time to time that helped provide the comprehensive coverage of CI characteristics reported in this article.

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Authors and Affiliations

  1. OINDP Consultancy, Rugby, UK

    S. C. Nichols

  2. Trudell Medical International, London, Ontario, N5V 5 G4, Canada

    J. P. Mitchell

  3. PPD Inc., Middleton, Wisconsin, USA

    C. M. Shelton

  4. MSP Corporation, St Paul, Minnesota, USA

    D. L. Roberts

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  1. S. C. Nichols
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  2. J. P. Mitchell
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  3. C. M. Shelton
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  4. D. L. Roberts
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Correspondence to J. P. Mitchell.

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Nichols, S.C., Mitchell, J.P., Shelton, C.M. et al. Good Cascade Impactor Practice (GCIP) and Considerations for “In-Use” Specifications. AAPS PharmSciTech 14, 375–390 (2013). https://doi.org/10.1208/s12249-012-9905-1

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