How Cold Is Cold Enough? Refrigeration of the Next-Generation Impactor to Prevent Aerosol Undersizing

Background: Heat transfer from impactor to aqueous aerosols causes underestimation of droplet size due to evaporation. Hence, pharmacopeia suggests cooling the impactor to 5°C, which is well below aerosol temperature. In this study, we assessed the droplet size at four different impactor temperatures under controlled ambient conditions to compare the compendial 5°C method with our in-house method, where the impactor is cooled to aerosol temperature. Materials and Methods: A single nebulizer/compressor unit was used throughout. It produced an aerosol at 17°C when operated at 50% RH and 23°C RT ambient conditions. Thirty-six experiments were conducted with saline, 9 each at impactor temperatures of 5°C, 10°C, 17°C, and 23°C. NaCl stage deposition was determined by conductometry, mass on stages by weighing. Moreover, a simulation was carried out to track aerosol temperature when entering the impactor. Results: Measuring at 23°C yields a significantly smaller mass median aerodynamic diameter (MMAD) than at 5°C-17°C. Despite elevated water condensation in the impactor at 5°C and 10°C, there was no increase in MMAD compared with 17°C. Instead, droplet size determination at 5°C led to significantly smaller values than at 17°C, probably due to distorted volumetric impactor flow rates at different impactor temperatures. Reevaluation of data with flow rates adjusted for impactor temperature (14.1 L/min at 5°C vs. 15.0 L/min at 23°C) led to indistinguishable results at 5°C-17°C. A computational fluid dynamics (CFD) simulation confirmed rapid cooling of the incoming air within the inlet and stage 1 and, with it, the systematic droplet undersizing due to reduced volumetric airflow using a cooled impactor. Conclusions: As long as the impactor temperature is at or below aerosol temperature, no effects on droplet size can be observed. Measuring at aerosol temperature yields the same results as at 5°C, but prevents condensation. However, cooling the impactor well below ambient temperature can cause a systematic error in the volumetric flow rate through the impactor if not corrected accordingly.