Development and calibration of a low-flow version of the Marple-Miller impactor (mmi™)

Cascade impactor analysis of drugs for inhalation in aerosol form is regarded by both European and U.S. pharmacopoeias as an important method to determine particle size-related information concerning dose that might be delivered to various parts of the respiratory tract. Existing measurements usually are made at flow rates in excess of 25 l/min, which are more representative of peak inspiratory flow rates achieved by adults. There is therefore a need for a low-flow impactor that can be used to evaluate drug delivery devices intended for use by infants or small children, or by those whose disease status prevents the achievement of higher inspiratory flow rates. A new version of the Marple-Miller impactor™ (MMI™) is described that meets this need, operating at either 4.9 or 12 l/min by the substitution of a different uppermost stage jet. A novel feature is the use of external stage collection cups instead of plates, enabling quantitative transfer of drug collecting on each stage for subsequent chemical assay. Calibration data and an assessment of inter-stage losses are presented for each of the flow rates