Aerodynamic particle size of metered-dose inhalers determined by the quartz crystal microbalance and the Andersen cascade impactor.

Given the rapid sizing capability and high sensitivity, the quartz crystal microbalance (QCM) cascade impactor has been evaluated for the size determination of metered-dose inhaler (MDI) aerosols. The effects of surfactants present in MDI formulations, crystal coating, particle bounce and crystal overloading on the QCM cascade impactor are investigated. To reduce particle bounce, it is necessary to coat the crystals and use new coated surfaces for each measurement. Mass median aerodynamic diameters (MMADs) obtained from the QCM cascade impactor are compared to those from the commonly used Andersen cascade impactor. For MDI formulations containing little or no surfactants, MMADs obtained from the QCM and Andersen cascade impactors are comparable. For MDI formulations containing a significant amount of surfactant (or any non-volatile excipients), the QCM cascade impactor measures the combined size distribution of the drug and non-volatile excipients. A technique is devised in this study to deduce the drug-only size distribution from the QCM impactor for surfactant-containing MDI formulations and show comparable results to the Andersen cascade impactor except for high drug load Intal. The QCM impactor has proved to be a useful tool for rapid size measurement of MDI formulations.