Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2003 December; 4(4): 425–433.
Published online 2003 September 2. doi:  10.1208/pt040454
PMCID: PMC2750647

Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: Comparison of andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 aerodynamic particle sizer aerosol spectrometer


The purpose of this research was to compare three different methods for the aerodynamic assessment of (1) chloroflurocarbon (CFC)-fluticasone propionate (Flovent), (2) CFC-sodium cromoglycate (Intal), and (3) hydrofluoroalkane (HFA)-beclomethasone dipropionate (Qvar) delivered by pressurized metered dose inhaler. Particle size distributions were compared determining mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction <4.7 μm aerodynamic diameter (FPF<4.7 μm). Next Generation Pharmaceutical Impactor (NGI)-size distributions for Flovent comprised finer particles than determined by Andersen 8-stage impactor (ACI) (MMAD=2.0±0.05 μm [NGI]; 2.8±0.07 μm [ACI]); however FPF<4.7 μm by both impactors was in the narrow range 88% to 93%. Size distribution agreement for Intal was better (MMAD=4.3±0.19 μm (NGI), 4.2±0.13 μm (ACI), with FPF<4.7 μm ranging from 52% to 60%. The Aerodynamic Particle Sizer (APS) undersized aerosols produced with either formulation (MMAD=1.8±0.07 μm and 3.2±0.02 μm for Flovent and Intal, respectively), but values of FPF<4.7 μm from the single-stage impactor (SSI) located at the inlet to the APS (82.9%±2.1% [Flovent], 46.4%±2.4% [Intal]) were fairly close to corresponding data from the multi-stage impactors. APS-measured size distributions for Qvar (MMAD=1.0±0.03 μm; FPF<4.7 μm=96.4% ±2.5%), were in fair agreement with both NGI (MMAD=0.9±0.03 μm; FPF<4.7 μm=96.7%±0.7%), and ACI (MMAD=1.2±0.02 μm, FPF<4.7 μm=98%±0.5%), but FPF<4.7 μm from the SSI (67.1%±4.1%) was lower than expected, based on equivalent data obtained by the other techniques. Particle bounce, incomplete evaporation of volatile constituents and the presence of surfactant particles are factors that may be responsible for discrepancies between the techniques.

Keywords: pressurized metered-dose inhaler, impactor, time-of-flight, aerodynamic size distribution, aerosol measurement

Full Text

The Full Text of this article is available as a PDF (488K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. USP 26-NF 21 . Chapter 601-Physical tests and determinations: aerosols. United States Pharmacopeia. Rockville, MD: United States Pharmacopeial Convention; 2003. pp. 2105–2123.
2. European Pharmacopeia . Section 2.9.18-Preparations for inhalation: aerodynamic assessment of fine particles. European Pharmacopeia. 3rd ed. Strasbourg, France: Council of Europe; 2002. pp. 113–124.
3. Rudolph G, Kobrich R, Stahlhofen W. Modelling and algebraic formulation of regional aerosol deposition in man. J Aerosol Sci. 1990;21(suppl 1):306–406.
4. Marple VA, Roberts DL, Romay FJ, Miller NC, Truman KG, Van Oort M, Olsson B, Holdroyd MJ, Mitchell JP, Hochrainer D. Next generation pharmacentical impactor. Part 1: Design. J Aerosol Med. 2003;16:283–299. doi: 10.1089/089426803769017659. [PubMed] [Cross Ref]
5. Marple VA, Olson BA, Santhanakrishman K, Mitchell JP, Murray SC, Hudson-Curtis BL. Next generation pharmaceutical impactor. Part 2: Archival calibration. J Aerosol Med. 2003;16:301–324. doi: 10.1089/089426803769017668. [PubMed] [Cross Ref]
6. Mitchell JP, Costa PA, Waters S. An assessment of an Andersen mark-II cascade impactor. J Aerosol Sci. 1988;19(2):213–231. doi: 10.1016/0021-8502(88)90224-8. [Cross Ref]
7. Mitchell JP. Drug Delivery to the Lungs—XI. London, UK: Aerosol Society; 2000. The next generation impactor (NGI): results from the evaluation of prototype instruments with pressurized metered dose inhaler (pMDI)-based formulations; pp. 223–226.
8. Miller NC, Roberts DL, Marple VA. The ‘Service Head’ approach to automating the next generation pharmaceutical impactor: proof of concept. In: Dalby RN, Byron PR, Peart J, Farr SJ, editors. Respiratory Drug Delivery VIII. Raleigh, NC: Davis Horwood International; 2002. pp. 521–523.
9. Stein SW, Beck TJ, Gabrio BJ. Evaluation of a new aerodynamic particle sizer for MDI size distribution measurements. In: Dalby RN, Byron PR, Farr SJ, Peart J, editors. Respiratory Drug Delivery VII. Raleigh, NC: Serentec Press; 2000. pp. 283–286.
10. Mitchell JP, Nagel MW. Time-of-flight aerodynamic particle size analyzers: their use and limitations for the evaluation of medical aerosols. J Aerosol Med. 1999;12(4):217–240. [PubMed]
11. Heitbrink WA, Baron PA, Willeke K. Coincidence in time-of-flight spectrometers: phantom particle creation. Aerosol Sci Technol. 1991;14(1):112–126. doi: 10.1080/02786829108959476. [Cross Ref]
12. Mitchell JP, Nagel MW. An assessment of the API Aerosizer for the real-time measurement of medical aerosols from pressurized metered-dose inhaler (pMDI) systems. Aerosol Sci Technol. 1996;25(4):411–423. doi: 10.1080/02786829608965406. [Cross Ref]
13. Mitchell JP, Nagel MW, Archer AD. Size analysis of a pressurized metered dose inhaler-delivered suspension formulation by an API Aerosizer time-of-flight aerodynamic particle size analyzer. J Aerosol Med. 1999;12(4):255–264. doi: 10.1089/jam.1999.12.255. [PubMed] [Cross Ref]
14. Nagel MW, Wiersema KJ, Bates SL, Mitchell JP. Size analysis of a pressurized metered dose inhaler-delivered solution formulation by an Aerosizer-LD time-of-flight aerosol spectrometer. J Aerosol Med. 2002;15(1):75–85. doi: 10.1089/08942680252908601. [PubMed] [Cross Ref]
15. Stein SW, Gabrio BJ, Oberreit D, Hairston P, Myrdal PB, Beck TJ. An evaluation of mass-weighted size distribution measurements with the model 3320 aerodynamic particle sizer. Aerosol SciTechnol. 2002;36(7):845–854. doi: 10.1080/02786820290092087. [Cross Ref]
16. Thiel CG. Cascade impactor data and the lognormal distribution: Nonlinear regression for a better fit. J Aerosol Med. 2002;15(4):369–378. doi: 10.1089/08942680260473443. [PubMed] [Cross Ref]
17. Dolovich MB. Aerosol delivery devices and airways/lung deposition. In: Schleimer RP, O'Byrne P, Szeffler S, Bratsand R, editors. Inhaled Steroids in Asthma. New York, NY: Marcel Dekker; 2001. pp. 169–210.
18. Cripps A, Riebe M, Schulze M, Woodhouse R. Pharmaceutical transition to non-CFC pressurized metered dose inhalers. Respir Med. 2000;94(suppl B):3–9. [PubMed]
19. Kamiya A, Sakagami M, Hindle M, Byron PR. Particle sizing with the next generation impactor: a study of VancerilTM metered dose inhaler. J Aerosol Med. 2003;16(2):216–216.
20. Marple VA, Olson BA, Miller NC. The role of inertial particle collectors in evaluating pharmaceutical aerosol delivery systems. J Aerosol Med. 1998;11(suppl 1):139–153. [PubMed]
21. Chew NYK, Bagster DF, Chan H-K. Effect of particle size, air flow and inhaler device on the aerosolisation of disodium cromoglycate powders. Int J Pharm. 2000;206:75–83. doi: 10.1016/S0378-5173(00)00516-0. [PubMed] [Cross Ref]
22. Morén F. Drug deposition of pressurized inhalation aerosols. I. Influence of actuator tube design. Int J Pharm. 1978;1:205–212. doi: 10.1016/0378-5173(78)90009-1. [Cross Ref]
23. Morén F, Andersson J. Fraction of dose exhaled after administration of pressurized aerosols. Int J Pharm. 1980;6:295–300. doi: 10.1016/0378-5173(80)90112-X. [Cross Ref]
24. Hickey AJ, Evans RM. Aerosol generation from propellantdriven metered dose inhalers. In: Hickey AJ, editor. Inhalation Aerosols: Physical and Biological Basis for Therapy. New York, NY: Marcel Dekker; 1996. pp. 417–439.
25. Leach CT. Enhanced drug delivery through reformulating MDIs with HFA propellants—Drug deposition and its effect on pre-clinical and clinical programs. In: Dalby RN, Byron PR, Farr SJ, editors. Respiratory Drug Delivery-V. Buffalo Grove, IL: Interpharm Press; 1996. pp. 133–144.
26. Gupta A, Myrdal PB, Stein SW, Gabrio BJ, Beck TJ. Comparison of the TSI model 33 06 impactor inlet with the Andersen cascade impactor by testing solution metered dose inhalers. In: Dalby RN, Byron PR, Farr SJ, Peart J, editors. Respiratory Drug Delivery-VIII. Raleigh, NC: Davis Horwood; 2002. pp. 659–662.
27. Peters TM, Leith D. Concentration measurement and counting efficiency of the aerodynamic particle sizer 3321. J Aerosol Sci. 2003;34(5):627–634. doi: 10.1016/S0021-8502(03)00030-2. [Cross Ref]
28. TSI Inc. Manual for the model 3302A Diluter. Rev B. St Paul, MN: TSI Inc; 2003.
29. Baron PA, Mazumder MK, Cheng YS. Direct-reading techniques using optical particle detection. In: Willeke K, Baron PA, editors. Aerosol Measurement. New York, NY: Van Nostrand Reinhold; 1993. pp. 381–409.

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists