William H. Doub1, Vibhaker Shah2, Susan Limb3, Changning Guo1, Xiaofei Liu1, Diem Ngo1
1US FDA/OMPT/CDER/OPS/OTR/ Division of Pharmaceutical Analysis, Saint Louis, MO
2US FDA/OMPT/CDER/OC/OMPQ/DGMPA/NDMAB, Silver Spring, MD
3US FDA/OMPT/CDER/OND/ODEII/Division of Pulmonary, Allergy, and Rheumatology Products, Silver Spring, MD
Received 20 December 2013; revised 18 July 2014; accepted 7 August 2014
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.24167
ABSTRACT: As a result of the Montreal Protocol on Substances that Deplete the Ozone Layer, manufacturers of metered dose inhalers began reformulating their products to use hydrofluoroalkanes (HFAs) as propellants in place of chlorofluorocarbons (CFCs). Although the new products are considered safe and efficacious by the US Food and Drug Administration (FDA), a large number of complaints have been registered via the FDA’s Adverse Events Reporting System (FAERS)—more than 7000 as of May 2013. To develop a better understanding of the measurable parameters that may, in part, determine in vitro performance and thus patient compliance, we compared several CFC- and HFA-based products with respect to their aerodynamic performance in response to changes in actuator cleaning interval and interactuation delay interval. Comparison metrics examined in this study were: total drug delivered ex-actuator, fine particle dose (<5 µm), mass median aerodynamic diameter, plume width, plume temperature, plume impaction force, and actuator orifice diameter. Overall, no single metric or test condition distinguishes HFA products from CDC products, but, for individual products tested, there were a combination of metrics that differentiated one from another. © Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.