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Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs

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Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products

Abstract

The previous chapters have focused primarily on the application of ­AIM-­EDA in the quality control part of an OIP lifecycle. An AIM-based approach would also be desirable for comparing and ideally correlating in vitro APSD-derived metrics with the likely particle deposition profile in the HRT that in turn should be linked with clinical effects. In addition to selection of appropriate size boundaries between coarse and fine particle mass fractions, there is the consideration of modifying the reduced impactor to add a third subfraction that relates to the measurement of the fraction of the dose ex-inhaler that comprises extra-fine submicron-sized particles. Furthermore, adapting the AIM concept to an alternative approach in which more clinically pertinent measures of in vitro performance are obtained raises the prospect of making the aerosol transport system more realistic in terms of human anatomy. An obvious move in this direction would be to replace the USP/Ph.Eur. induction port that was designed primarily to support OIP QC-based testing with an inlet that more appropriately models aerosol flow through the human oropharyngeal/nasopharyngeal region, depending upon patient age being studied. This chapter describes key features of how so-called AIM-pHRT systems might be constructed. The prefix “p” refers to the potential application of this alternative AIM-based approach. It will be for sponsors of this type of CI-based measurement application to undertake validation studies with their products. Such studies will likely compare measurements with AIM-pHRT apparatus(es) with both full-resolution CI data and particle deposition profiles utilizing imaging methods, such as gamma scintigraphy, positron emission tomography, or possibly magnetic resonance imaging. The chapter concludes with the results from the first laboratory-based evaluation of an AIM-­pHRT system based on the ACI equipped with the recently commercialized “Alberta Idealized Throat” (AIT) adult upper airway geometry.

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Author information

Authors and Affiliations

  1. Trudell Medical International, 725 Third Street, London, ON, N5V 5G4, Canada

    Jolyon P. Mitchell

  2. Copley Scientific Limited, Colwick Quays Business Park, Private Road No. 2, Colwick, Nottingham, NG4 2JY, UK

    Mark Copley

  3. Melbourn Scientific Limited, Saxon Way, Melbourn, SG8 6DN, UK

    Derek Solomon

Authors
  1. Jolyon P. Mitchell
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  2. Mark Copley
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  3. Derek Solomon
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Correspondence to Jolyon P. Mitchell .

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Editors and Affiliations

  1. , Analytical Development, Boehringer Ingelheim Pharmaceutical, Inc, Ridgebury Rd 900, Ridgefield, 06877, Connecticut, USA

    Terrence P. Tougas

  2. Trudell Medical International, Third Street 725, London, N5V 5G4, Ontario, Canada

    Jolyon P. Mitchell

  3. Drinker Biddle & Reath LLP, K Street, N.W. 1500, Washington, D.C., 20005, District of Columbia, USA

    Svetlana A. Lyapustina

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Mitchell, J.P., Copley, M., Solomon, D. (2013). Applying the AIM Concept in Support of Developing Improved In Vitro–In Vivo Relationships for OIPs. In: Tougas, T., Mitchell, J., Lyapustina, S. (eds) Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-6296-5_12

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