Assessing the temperature of thermally generated inhalation aerosols.
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.
Noymer
Peter D
PD
Alexza Pharmaceuticals, Inc., 2091 Stierlin Court, Mountain View, CA 94043, USA. pnoymer@alexza.com
Myers
Dan J
DJ
Cassella
James V
JV
Timmons
Ryan
R
D000280:Administration, Inhalation; D000336:Aerosols; D016503:Drug Delivery Systems; D004867:Equipment Design; D006801:Humans; D006813:Humidity; D009330:Nebulizers and Vaporizers; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D013678:Technology, Pharmaceutical; D013696:Temperature
D000336:Aerosols; D004364:Pharmaceutical Preparations