Evaluations Of Nebulizer Particle Size Distribution Utilizing Cascade Impactor And Laser Diffraction-the Effects Of Temperature, Humidity And Particle Sizes

Analysis of particle size and size distribution is critical for the development of inhalation formulation. Laser diffraction(LD) and Next Generation Impactor(NGI) analysis are commonly used for the evaluation of the size and size distribution of inhalation particles.However, the results of such analysis are dependent on several factors. We investigated the effects of temperature, humidity and particle size on the size assessment of particles generated by nebulizer using LD(Spraytec) and NGI, and differences of the results between these two methods. Following are the main contents of this study:(1) We investigated the effect of temperature on the assessment of size distribution(PSD) of particles by NGI. There were significant differences of the MMAD(mass median aerodynamic diameter) and FPF(fine particle fraction) between 5 ℃ and 25 ℃. The MMAD was increased by 30.89%(Ventolin) and 32.34%(self-made levalbuterol sulfate inhalation solution), and the FPF was reduced by 13.55%(Ventolin) and 5.17%(self-made levalbuterol sulfate inhalation solution) at 5 ℃ compared to those at 25 ℃. It is inferred that the particles could be shrunk because of water evaporation during the measurement at25 ℃.(2) We investigated the effect of temperature, humidity and particle size on the assessment of particle size and size distribution by LD(Spraytec). There was an increase of the particle size at higher temperature or lower humidity. The particles with diameters smaller than 1μm were detectable at 5 °C or relative humidity >90%, however, these particles were undetectable when temperature increased to 39 °C or at relative humidity of 30-45%. The results showed that small particles are easier to disappear duo to water evaporation at high temperature or low humidity. In addition, the influence of the temperature or humidity is related to the nebulizer type.(3) We investigated the difference between the nebulizer particle size distribution(PSD)measured by NGI and Spraytec when NGI in series with Spraytec.(4) Choosing three types of jet nebulizers and two kinds of inhaled drug formulations. Arelatively good correlation(R2=0.977) was observed for the largest particle size nebulizer(PARI TIA(8.6 μm)) compared with PARI LC(2.2 μm) and PARI LC(2.9 μm).Conclusion: the ambient environment and 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.