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

  • J . David Christopher
  • Rajni B. Patel
  • Jolyon P. Mitchell
  • Terrence P. Tougas
  • Adrian P. Goodey
  • Jorge Quiroz
  • Patrik U. Andersson
  • Svetlana Lyapustina
Research Article
  • 44 Downloads

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.

KEY WORDS

oral inhaler testing abbreviated impactor measurement mass median aerodynamic diameter efficient data analysis method sensitivity 

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

Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • J . David Christopher
    • 1
  • Rajni B. Patel
    • 2
  • Jolyon P. Mitchell
    • 3
  • Terrence P. Tougas
    • 4
  • Adrian P. Goodey
    • 5
  • Jorge Quiroz
    • 1
  • Patrik U. Andersson
    • 6
  • Svetlana Lyapustina
    • 7
  1. 1.Research CMC StatisticsMerck Research LaboratoriesWest PointUSA
  2. 2.Independent consultantBrookfieldUSA
  3. 3.Jolyon Mitchel Inhaler Consulting Services, Inc.LondonCanada
  4. 4.Independent ConsultantNew MilfordUSA
  5. 5.Biopharmaceutics and Specialty Dosage FormsMerck & Co., Inc.RahwayUSA
  6. 6.Pharmaceutical Technology & DevelopmentAstraZenecaGothenburgSweden
  7. 7.Pharmaceutical Practice GroupDrinker Biddle & Reath LLPWashington DCUSA

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