Effects of extreme temperatures on drug delivery of albuterol sulfate hydrofluoroalkane inhalation aerosols

Purpose. The effects of extreme temperatures on drug delivery of two albuterol sulfate hydrofluoroalkane, metered-dose inhalers (MDIs) were evaluated. Methods. Three Proventil HFA and three Ventolin HFA MDIs were stored at room temperature and served as controls while three of each product were placed in the trunk of a vehicle in Tucson, Arizona. The temperature in the vehicle was monitored for six months. Product performance for each of the MDIs was evaluated at room temperature. An additional study was performed to investigate the performance of the two products when actuated at 4, 22, 47, and 60 °C. Results. The products subjected to extreme environmental temperatures had a modest increase in propellant-leak rate, but the emitted-particle size, dose per actuation, respirable mass, and nonrespirable mass were unaffected. The inhalers tested at temperatures outside the recommended storage conditions exhibited a decrease in particle size, dose per actuation, shot weight and nonrespirable mass as temperature increased. Conversely, increased temperature caused an increase in respirable mass. Conclusion. Despite exposure to extreme temperatures exceeding the manufacturers' recommended storage conditions, drug delivery from Proventil HFA and Ventolin HFA MDIs was not significantly altered. However, drug delivery did change appreciably when the inhalers were tested at different temperatures outside recommended storage conditions.