• Publication Date: 04/01/2020
  • Author(s):
    Christopher, J. David Doub, William H. Goodey, Adrian Mitchell, Jolyon P.
  • Organization(s):
    Jolyon Mitchell Inhaler Consulting Services, Inc. Merck OINDP In Vitro Analysis
  • Article Type: Technical Articles
  • Subjects: Industry Issues and Trends, Particle Characterization, Product Development/Formulation, Testing, Validation, and Regulatory Compliance
The first in a series of articles from the IPAC-RS Cascade Impaction Working Group concerning the limitations of metrics commonly used in the assessment of aerodynamic particle size distributions (APSDs) of orally inhaled products (OIPs). The current article discusses the surprisingly limited utility of the fine particle dose metric in quality control.

The insensitivity of FPD to shifts in inhaler APSD is illustrated and underlying causes have been discussed. Data from eight different products are examined. In conclusion, FPD cannot be used alone as a metric for APSD quality control. FPD can be used to control the mass-dimension of the APSD, but must be used in conjunction with an orthogonal metric sensitive to changes in the size-dimension (such as MMAD). Importantly, supplementing FPD with metrics such as ISM or material balance (total mass ex-inhaler), neither of which are sensitive to APSD size changes, is not sufficient.

Read part two – Cascade impactor stage groupings: Poor decisions from degraded data

Read part three – Efficient data analysis (EDA): Size, mass and common sense

Read an interview with the authors about reactions to these articles

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