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

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.