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Discriminating Ability of Abbreviated Impactor Measurement Approach (AIM) to Detect Changes in Mass Median Aerodynamic Diameter (MMAD) of an Albuterol/Salbutamol pMDI Aerosol

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Abstract

This article reports on results from a two-lab, multiple impactor experiment evaluating the abbreviated impactor measurement (AIM) concept, conducted by the Cascade Impaction Working Group of the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of this experiment was to expand understanding of the performance of an AIM-type apparatus based on the Andersen eight-stage non-viable cascade impactor (ACI) for the assessment of inhalation aerosols and sprays, compared with the full-resolution version of that impactor described in the pharmacopeial compendia. The experiment was conducted at two centers with a representative commercially available pressurized metered dose inhaler (pMDI) containing albuterol (salbutamol) as active pharmaceutical ingredient (API). Metrics of interest were total mass (TM) emitted from the inhaler, impactor-sized mass (ISM), as well as the ratio of large particle mass (LPM) to small particle mass (SPM). ISM and the LPM/SPM ratio together comprise the efficient data analysis (EDA) metrics. The results of the comparison demonstrated that in this study, the AIM approach had adequate discrimination to detect changes in the mass median aerodynamic diameter (MMAD) of the ACI-sampled aerodynamic particle size distribution (APSD), and therefore could be employed for routine product quality control (QC). As with any test method considered for inclusion in a regulatory filing, the transition from an ACI (used in development) to an appropriate AIM/EDA methodology (used in QC) should be evaluated and supported by data on a product-by-product basis.

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Abbreviations

ACI:

Andersen cascade impactor (full-resolution, 8-stage)

AIM:

Abbreviated impactor measurement

API:

Active pharmaceutical ingredient

APSD:

Aerodynamic particle size distribution

CI:

Cascade impactor

EDA:

Efficient data analysis

EPAG:

European pharmaceutical aerosol group

FPD:

Fine particle dose

IPAC-RS:

International pharmaceutical aerosol consortium on regulation and science

ISM:

Impactor-sized mass (i.e., API mass collected from impactor stages with a defined upper cut-off)

LPM:

Large particle mass

MMAD:

Mass median aerodynamic diameter

OIP:

Orally inhaled product

pHRT:

Potential human respiratory tract (when referring to aerosol deposition sites)

pMDI:

Pressurized metered dose inhaler

QC:

Quality control

RMSE/b:

Root mean square error divided by slope (from regression analysis)

SPM:

Small particle mass

TM:

Total mass (i.e., API mass collected from actuator and all of the impactor stages)

USP:

United States pharmacopeia

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Acknowledgments

The authors appreciate support of the IPAC-RS Board of Directors and Cascade Impaction Working Group in conceiving, conducting, and analyzing the study. Special thanks go to the three laboratories that donated their expertise and resources for the study, especially to David Mark (PPD), Michelle Rick (PPD), Cindy Drew (PPD), Kevin Rauschenberger (PPD) and Michael Estrella (BI), Ellen Christman (BI), David Giordano (BI), Jennifer Whitcomb (BI), and Jeffrey Trenck (BI). The authors also thank William Doub for his careful review and thoughtful comments on the draft manuscript, and to Gareth Hardwell, for discussions of early drafts.

Author information

Authors and Affiliations

  1. Research CMC Statistics, Merck Research Laboratories, West Point, Pennsylvania, USA

    J . David Christopher & Jorge Quiroz

  2. Independent consultant, Brookfield, Connecticut, USA

    Rajni B. Patel

  3. Jolyon Mitchel Inhaler Consulting Services, Inc., London, Ontario, Canada

    Jolyon P. Mitchell

  4. Independent Consultant, New Milford, Connecticut, USA

    Terrence P. Tougas

  5. Biopharmaceutics and Specialty Dosage Forms, Merck & Co., Inc., Rahway, New Jersey, USA

    Adrian P. Goodey

  6. Pharmaceutical Technology & Development, AstraZeneca, Gothenburg, Sweden

    Patrik U. Andersson

  7. Pharmaceutical Practice Group, Drinker Biddle & Reath LLP, 1500 K Street, NW, Suite 1100, Washington DC, District of Columbia, 20005-1209, USA

    Svetlana Lyapustina

Authors
  1. J . David Christopher
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  2. Rajni B. Patel
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  3. Jolyon P. Mitchell
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  4. Terrence P. Tougas
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  8. Svetlana Lyapustina
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Correspondence to Svetlana Lyapustina.

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David Christopher, J..., Patel, R.B., Mitchell, J.P. et al. Discriminating Ability of Abbreviated Impactor Measurement Approach (AIM) to Detect Changes in Mass Median Aerodynamic Diameter (MMAD) of an Albuterol/Salbutamol pMDI Aerosol. AAPS PharmSciTech 18, 3296–3306 (2017). https://doi.org/10.1208/s12249-017-0814-1

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