Effects of Temperature and Humidity on Laser Diffraction Measurements to Jet Nebulizer and Comparison with NGI

Abstract

Laser diffraction (LD) and next generation impactor (NGI) are commonly used for the evaluation of inhaled drug formulations. In this study, the effect of temperature and humidity on the assessment of the nebulizer particle size distribution (PSD) by LD was investigated, and the consistency between NGI and LD measurements was evaluated. There was an increase in particle size with higher temperature or lower humidity. The particle population with a diameter less than 1 μm was significant at a temperature of 5°C or at relative humidity >90%; however, the same particle population became undetectable when temperature increased to 39°C or at relative humidity of 30-45%. The results of the NGI and LD measurements of aerosol generated from three types of jet nebulizers were compared. A poor correlation between the NGI and LD measurements was observed for PARI LC (2.2 μm) (R (2) = 0.893) and PARI LC (2.9 μm) (R (2) = 0.878), while a relatively good correlation (R (2) = 0.977) was observed for the largest particle size nebulizer (PARI TIA (8.6 μm)). We conclude that the ambient environment and the nebulizer have significant impacts on the performance and consistency between these instruments. These factors should be controlled in the evaluation of inhaled aerosol drug formulations when these instruments are used individually or in combination.

Keywords: impactor; jet nebulizer; laser diffraction; particle size distribution.

Fig. 1

Front side view of the experimental set-up for simultaneous particle size distribution measurements with NGI and Spraytec

Fig. 2

A comparison of temperature and humidity on particle size characterization by laser diffraction. a, b Depict the effects of temperature on the assessment of formulation ResQ-1 and PARI TIA (8.6 μm). c, d Depict the effects of humidity on the assessment of Ventolin and PARI LC (2.9 μm). a Shows the cumulative distribution of particle volume (formulation ResQ-1 and PARI TIA (8.6 μm)), the curve shift right with temperature increase, and b is the frequency distribution of particle volumes (formulation ResQ-1 and PARI TIA (8.6 μm)). There were two particle populations measured at 5 and 25 ± 2°C; however, the particle population under 1 μm is below the detection limit when measured at 39 ± 2°C. c Shows the cumulative distribution of particle volumes (Ventolin and PARI LC (2.9 μm)), the curve shift right with relative humidity decrease, and d is the frequency distribution of particle volume (Ventolin and PARI LC (2.9 μm)). There were two particle populations when measured at RH > 90% and RH 30–45%

Fig. 3

The comparison of NGI separate and in series tests. a PARI LC (2.2 μm) and formulation ResQ-1. b PARI LC (2.2 μm) and Ventolin

Fig. 4

Comparison of the cumulative frequency with simultaneous measurements for NGI and Spraytec. a Formulation ResQ-1 and PARI LC (2.2 μm); b Ventolin and PARI LC (2.2 μm); c formulation ResQ-1 and PARI LC (2.9 μm); d Ventolin and PARI LC (2.9 μm); e formulation ResQ-1 and PARI TIA (8.6 μm); f Ventolin and PARI TIA (8.6 μm)

Fig. 5

The correlation curves of NGI and Spraytec for nebulizers with different particle sizes