Assessing the Temperature of Thermally Generated Inhalation Aerosols

Abstract

Abstract

Background:

Condensation aerosols are produced when a drug is vaporized and then cools in the inhalation air. Because energy is applied to vaporize the drug, there is a potential concern that the air temperature might not be well tolerated. A literature review indicates that the proper metric for this is the wet-bulb temperature (T_wb) of the inhaled air. T_wb measures the total energy of the air, including moisture content, and reflects the potential impact on safety and tolerability.

Methods:

The Staccato^® system (Alexza Pharmaceuticals, Mountain View, CA) uses thermal vaporization for aerosol generation and was used in a series of studies to characterize the peak transient value (peak T_wb) of the air coming out of the device. These studies evaluated peak T_wb over a range of air flow rates (15–45 L/min), ambient conditions [15–30°C and 15 to 90% relative humidity (RH)] and vaporization temperatures.

Results:

Under nominal conditions (30 L/min air flow, 25°C and 50% RH), peak T_wb was 28.8 ± 0.6°C (mean ± standard deviation). Over the range of operating conditions tested, mean values for peak T_wb ranged from 26.2 to 33.3°C with similarly low variances. When operated under a combination of extreme conditions, peak T_wb was measured to be 39.9 ± 0.1°C (mean ± standard deviation).

Conclusions:

Technical standards indicate that the upper limit on inhaled T_wb for safety and tolerability is 50°C, and inhalation at that temperature can be sustained for 1 h. Peak values of T_wb from the Staccato system are well below that threshold, approximately 30°C at nominal conditions and approximately 40°C at a combination of extreme conditions. Moreover, the peak lasts for only a few seconds, well under the time limit of 1 h. These results suggest that aerosols generated with the Staccato system will be safe and well tolerated.