Effects of Environmental and Mechanical Variations on Particle Size Distribution of Albuterol HFA Inhalers

BACKGROUND: The purpose of this study was to evaluate how factors (ambient temperature, shaking the inhaler before use, suspension of the inhaler in water, and the variation over the lifetime of the inhaler) affect the particle-size distributions from albuterol HFA inhalers.

METHODS: We used a laser particle-size analyzer to measure the percentage of particles in the 1- to 5-μm range (fine-particle fraction) serially 2,500 times per second to obtain a window of useful measurements with each inhaler actuation. We compared the inhaler performance results as follows: cold versus hot, full versus partial versus empty inhaler actuations, shaken versus unshaken, and inhaler characteristics after water submersion.

RESULTS: The effect of temperature was as follows: fine-particle fraction was 14.4% at 5°C, 37.9% at 24 - 25°C, and 38.1% at 45°C. The fine-particle fraction at the start, middle, end, and past the end of the inhaler’s rated lifetime were 37.9, 26.3, 27.9, and 22.0%, respectively. Shaking the inhaler did not improve the inhaler’s fine-particle fraction. Submerging the inhaler reduced the fine-particle fraction to 14.3% without purging and to 20.5% with purging compared with the 42.1% for the control inhaler, which was not submerged.

CONCLUSIONS: Temperature made a difference, with cold inhalers producing a lower fine-particle fraction. The early portion of the inhaler had a better fine-particle fraction than the middle and end of the inhaler’s lifespan. We could not demonstrate that shaking the inhaler had a significant effect on the fine-particle fraction. Submerging the inhaler in water significantly reduced the fine-particle fraction.