Optimized inhalation aerosols. II. Inertial testing methods for particle size analysis of pressurized inhalers.

Pressurized metered dose inhaler (MDI) output from three different albuterol formulations was characterized using three inertial separation devices. Results were compared for the Delron six-stage cascade impactor (DC16), the Andersen Mark II eight-stage impactor (AC18), and Copley's twin-stage liquid impinger (LI). None of the devices tested in this study was ideal in all respects. All devices could differentiate between formulations in terms of respirable doses (albuterol amount with aerodynamic diameters less than 5.5 through 6.4 microns). Only the high-flow rate LI could differentiate among all three formulations when data were presented in terms of respirable percentage (RP) of drug collected. Values for RP were in excellent agreement for the independently calibrated impactors when the same evaporation chamber was used atop the impactors. The LI appeared to overestimate values for RP in vivo. Results are discussed in light of the debate surrounding the revision of USP aerosol testing requirements. Rigorous specifications for evaporation chambers and methodologies are necessary for meaningful inter- and intra-laboratory comparison of results when any of these devices are used.