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The Abbreviated Impactor Measurement (AIM) Concept: Part II—Influence of Evaporation of a Volatile Component—Evaluation with a “Droplet-Producing” Pressurized Metered Dose Inhaler (pMDI)-Based Formulation Containing Ethanol as Cosolvent

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Abstract

The abbreviated impactor measurement (AIM) concept is a potential solution to the labor-intensive full-resolution cascade impactor (CI) methodology for inhaler aerosol aerodynamic particle size measurement. In this validation study, the effect of increasing the internal dead volume on determined mass fractions relating to aerodynamic particle size was explored with two abbreviated impactors both based on the Andersen nonviable cascade impactor (ACI) operating principle (Copley fast screening Andersen impactor [C-FSA] and Trudell fast screening Andersen impactor [T-FSA]). A pressurized metered dose inhaler-delivered aerosol producing liquid ethanol droplets after propellant evaporation was chosen to characterize these systems. Measures of extrafine, fine, and coarse particle mass fractions from the abbreviated systems were compared with corresponding data obtained by a full-resolution ACI. The use of liquid ethanol-sensitive filter paper provided insight by rendering locations visible where partly evaporated droplets were still present when the “droplet-producing” aerosol was sampled. Extrafine particle fractions based on impactor-sized mass were near equivalent in the range 48.6% to 54%, comparing either abbreviated system with the benchmark ACI-measured data. The fine particle fraction of the impactor-sized mass determined by the T-FSA (94.4 ± 1.7%) was greater than using the C-FSA (90.5 ± 1.4%) and almost identical with the ACI-measured value (95.3 ± 0.4%). The improved agreement between T-FSA and ACI is likely the result of increasing the dead space between the entry to the induction port and the uppermost impaction stage, compared with that for the C-FSA. This dead space is needed to provide comparable conditions for ethanol evaporation in the uppermost parts of these impactors.

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Abbreviations

ACI:

Andersen cascade impactor

AIM:

abbreviated impactor measurement

API:

active pharmaceutical ingredient

APSD:

aerodynamic particle size distribution

BDP:

beclomethasone dipropionate

CI:

cascade impactor

C-FSA:

Copley fast screening Andersen impactor

CPF*:

coarse particle fraction (based on impactor-sized mass)

EPF*:

extrafine particle fraction (based on impactor-sized mass)

FPF*:

fine particle fraction (based on impactor-sized mass)

MMAD:

mass median aerodynamic diameter of impactor-sized aerosol

pMDI:

pressurized metered dose inhaler

T-FSA:

Trudell fast screening Andersen impactor

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Acknowledgements

The authors acknowledge the support of Copley Scientific Ltd. for the C-FSA and the advice and support of Mark Copley and Daryl Roberts (MSP Corp., St. Paul, MN, USA) during the development and execution of this investigation. They also wish to thank Steven Stein (3M Drug Delivery Systems, St. Paul, MN, USA) for the supply of ethanol-sensitive paper as well as for additional discussions as the work progressed.

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Authors and Affiliations

  1. Trudell Medical International, 725 Third Street, London, ON, Canada, N5V 5G4

    J. P. Mitchell, M. W. Nagel, V. Avvakoumova, H. MacKay & R. Ali

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  1. J. P. Mitchell
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  2. M. W. Nagel
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  3. V. Avvakoumova
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  4. H. MacKay
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  5. R. Ali
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Correspondence to J. P. Mitchell.

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Mitchell, J.P., Nagel, M.W., Avvakoumova, V. et al. The Abbreviated Impactor Measurement (AIM) Concept: Part II—Influence of Evaporation of a Volatile Component—Evaluation with a “Droplet-Producing” Pressurized Metered Dose Inhaler (pMDI)-Based Formulation Containing Ethanol as Cosolvent. AAPS PharmSciTech 10, 252–257 (2009). https://doi.org/10.1208/s12249-009-9201-x

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