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A Distribution-Based Metric for Quantifying Dispersibility in Dry Powder Inhalers.

Grace Xia1, Bhanuz Dechayont1, Linze Che1

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 1007 E. Huron St., Ann Arbor, MI 48104, USA.

Pharmaceutics
|March 28, 2026
PubMed
Summary
This summary is machine-generated.

The Wasserstein distance quantifies dry powder inhaler aerosol dispersibility, offering a reproducible method for optimizing inhaler formulations and device designs. This approach aids in evaluating powder dispersion efficiency across various conditions.

Keywords:
Wasserstein distanceaerosol size distributioncascade impactiondry powder inhalerlaser diffractionoptimal transportpowder dispersibilitypulmonary drug delivery

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Area of Science:

  • Pharmaceutical Technology
  • Aerosol Science
  • Materials Science

Background:

  • Evaluating aerosol dispersibility in dry powder inhalers (DPIs) is crucial for effective lung delivery.
  • Variations in particle properties and device resistance significantly impact aerodynamic performance.
  • Current methods like cascade impaction have limitations in throughput and experimental burden for systematic screening.

Purpose of the Study:

  • To introduce and validate a novel framework using the Wasserstein distance (Earth Mover's Distance) for quantifying aerosol dispersibility.
  • To establish a mathematically rigorous, distribution-based metric relative to a material-specific maximally dispersed reference state.
  • To enable systematic comparison of dispersion efficiency across different DPI formulations and device operating conditions.

Main Methods:

  • Spray-dried model powders (mannitol, trehalose, inulin) were characterized using laser diffraction.
  • A maximally dispersed reference state was established using a RODOS dry dispersion module.
  • Aerosols were generated under varying conditions using an INHALER module, and Wasserstein-1 distance (W1) was computed.
  • Cascade impaction served as an orthogonal validation method.

Main Results:

  • The W1 metric effectively captured formulation-, device-, and flow-dependent dispersibility differences.
  • Crystalline mannitol showed higher, flow-rate-dependent W1 values compared to amorphous trehalose and inulin.
  • W1 results qualitatively correlated with cascade impaction metrics (MMAD, FPF), indicating its utility.

Conclusions:

  • The Wasserstein distance provides a physically interpretable, formulation-agnostic metric for aerosol dispersibility.
  • This framework enables reproducible evaluation and optimization of DPI formulations and inhaler designs.
  • Utilizes standard laser diffraction data for efficient screening and mechanistic understanding.