Experimental Evaluations of Internal Losses in ‘Miller’ Mixing Inlet Used to Enable Constant Flow Rate to a Cascade Impactor Whilst Allowing an Inhaler to be Tested for Emitted Aerosol Aerodynamic Particle Size Distribution (APSD) with Realistic Breathing Profiles

Cooper A1, Slator L2, Mitchell JP3 & Svensson, M4

1 Kindeva Drug Delivery, Derby Road, Loughborough, LE11 5SF, UK

2 Philips, Chichester Business Park, City Fields Way, Tangmere, Chichester PO20 2FT, UK

3 Jolyon Mitchell Inhaler Consulting Services Inc., 1154 St. Anthony Road, London, N6H 2R1, Canada

4 Emmace Consulting AB, Scheelevägen 22, 223 63 Lund, Sweden


The ‘Miller’ design of mixing inlet enables a cascade impactor to operate at constant flow rate whilst the inhaler-on-test can be evaluated at varying flow rates.  Two studies forming part of a cross-industry assessment of mixing inlet internal losses are reported, the first evaluating continuous medication delivery of salbutamol via a nebulizer, the other examining bolus delivery of pMDI-actuated beclomethasone dipropionate (BDP). The nebulizer was subjected to a standard adult breathing profile (inspiratory/expiratory ratio = 1:1; tidal volume = 500 ml; respiration frequency = 15/min; peak inspiratory flow rate = 24 L/min).  The pMDI was sampled at 30 L/min without mixing inlet and then at 40, 60 and 90 L/min with 10, 30 and 60 L/min compressed air added to the side-arm of the mixing inlet. In the nebulizer study, total mass recovered from a Next Generation Impactor (NGI) was 569.3 ± 82.2 μg.  Average losses in the mixing inlet therefore represented 0.26% of the mass recovered from the impactor. In the pMDI study, total mass recovered from the NGI components was 78.1 ± 2.0 μg BDP/actuation, and the mass recovered from the mixing inlet interior surfaces was 0.6 ± 0.2 μg BDP/actuation for measurements at 40, 60 and 90 L/min. Internal losses within the ‘Miller’ mixing inlet are <1% of the total mass of medication sampled by the impactor, and, from the pMDI study, these losses did not change significantly when the flow rate was increased through the mixing inlet to the impactor from 40 to 90 L/min.

Key Message

The ‘Miller’ mixing inlet enables a cascade impactor to operate at constant flow rate for emitted aerosol aerodynamic particle size distribution (APSD) determination whilst an inhaler-on-test can be evaluated mimicking patient breathing. Our cross-industry study evaluated internal losses within such mixing inlets, testing a representative nebulizer and a pMDI product.