AAPS PharmSciTech

, Volume 10, Issue 1, pp 252–257 | Cite as

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

  • J. P. Mitchell
  • M. W. Nagel
  • V. Avvakoumova
  • H. MacKay
  • R. Ali
Research Article

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.

Key words

cascade impactor inhaler testing particle evaporation particle size distribution 

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

Notes

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.

References

  1. 1.
    J. P. Mitchell, M. W. Nagel, V. Avvakoumova, H. Mackay, and R. Ali. The abbreviated impactor measurement (AIM) concept: part-1—influence of particle bounce and re-entrainment—evaluation with a mid-size range “dry” pressurized metered dose inhaler-based formulation. AAPS PharmSciTech. in press (2008).Google Scholar
  2. 2.
    European Pharmacopeia—section 2.9.18—preparations for inhalation: aerodynamic assessment of fine particles. European Pharmacopeia: 5th Edn. Council of Europe, 67075 Strasbourg, France, pp. 2799–2811 (2005).Google Scholar
  3. 3.
    United States Pharmacopeia; USP 30-NF 25; Chapter 601—physical tests and determinations: aerosols. United States Pharmacopeia, Rockville, MD, USA, pp. 220–240 (2007).Google Scholar
  4. 4.
    J. P. Mitchell. The abbreviated impactor measurement (AIM) concept for aerodynamic particle size distribution (APSD) in a quality-by-design (QbD) environment. Proc. Biennial IPAC-RS Conference, Bethesda, MD, USA. 2008. Available at http://www.ipacrs.com/ipac2008.html. Accessed 5 October 2008.
  5. 5.
    S. W. Stein, and J. S. Stefely. Reinventing metered dose inhalers: from poorly efficient CFC MDIs to highly efficient HFA MDIs. Drug Deliv. Technol. 31:46–51 (2003).Google Scholar
  6. 6.
    S. W. Stein, and P. B. Myrdal. A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J. Pharm. Sci. 93:2158–2175 (2004).PubMedCrossRefGoogle Scholar
  7. 7.
    P. B. Myrdal, E. Mogallian, J. P. Mitchell, M. Nagel, C. Wright, B. Kiser, M. Prell, M. Woessner, and S. W. Stein. Application of heated inlet extensions to the TSI 3306/3321 system: comparison with the Andersen cascade impactor and next generation impactor. J. Aerosol Med. 194:543–554 (2006).PubMedCrossRefGoogle Scholar
  8. 8.
    P. B. Myrdal, S. W. Stein, E. Mogalian, W. Hoye, and A. Gupta. Comparison of the TSI model 3306 impactor inlet with the Andersen cascade impactor: solution metered dose inhalers. Drug Dev. Ind. Pharm. 30:859–868 (2004).PubMedCrossRefGoogle Scholar
  9. 9.
    C. Leach. Enhanced drug delivery through reformulating MDIs with HFA propellants—drug deposition and its effect on preclinical and clinical programs. In R. N. Dalby, P. R. Byron, and S. J. Farr (eds.), Respiratory Drug Delivery—V, Interpharm, Buffalo Grove, IL, 1996, pp. 133–144.Google Scholar
  10. 10.
    S. W. Stein. Aiming for a moving target: challenges with impactor measurements of MDI aerosols. Int. J. Pharm. 3551–2:53–61 (2007).PubMedGoogle Scholar
  11. 11.
    US Federal Drug Administration (FDA). Draft guidance: metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products chemistry, manufacturing and controls documentation. Docket 98D-0997 (1998).Google Scholar
  12. 12.
    M. N. Nasr, D. L. Ross, and N. C. Miller. Effect of drug load and plate coating on the particle size distribution of a commercial albuterol metered dose inhaler (MDI) determined using the Andersen and Marple–Miller cascade impactors. Pharm. Res. 1410:1437–1443 (1997).PubMedCrossRefGoogle Scholar
  13. 13.
    A. Gupta, S. W. Stein, and P. B. Myrdal. Balancing ethanol cosolvent concentration with product performance in 134a-based pressurized metered dose inhalers. J. Aerosol Med. 162:167–174 (2003).PubMedCrossRefGoogle Scholar
  14. 14.
    K. W. Stapleton, and W. H. Finlay. Undersizing of droplets from a vented nebuliser caused by aerosol heating during transit through an Andersen impactor. J. Aerosol Sci. 301:105–109 (1999).CrossRefGoogle Scholar
  15. 15.
    M. Copley, M. Smurthwaite, D. L. Roberts, and J. P. Mitchell. Revised internal volumes to those provided by Mitchell JP and Nagel MW in “Cascade Impactors for the Size Characterization of Aerosols From Medical Inhalers: Their Uses and Limitations”. J. Aerosol Med. 183:364–366 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    V. Chavan, and R. Dalby. Novel system to investigate the effects of inhaled volume and rates of rise in simulated inspiratory air flow on fine particle output from a dry powder inhaler. AAPS PharmSci. 42:E6 (2002)Available at http://www.aapspharmsci.org/.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • J. P. Mitchell
    • 1
  • M. W. Nagel
    • 1
  • V. Avvakoumova
    • 1
  • H. MacKay
    • 1
  • R. Ali
    • 1
  1. 1.Trudell Medical InternationalLondonCanada

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