Effect of Sampling Volume on Dry Powder Inhaler (DPI)-Emitted Aerosol Aerodynamic Particle Size Distributions (APSDs) Measured by the Next-Generation Pharmaceutical Impactor (NGI) and the Andersen Eight-Stage Cascade Impactor (ACI)

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• 作者：Hlack Mohammed (1)
  Daryl L. Roberts (2)
  Mark Copley (3)
  Mark Hammond (4)
  Steven C. Nichols (5)
  Jolyon P. Mitchell (6)
  
• 关键词：cascade impactor ; compendial method ; dry powder inhaler ; sample volume
• 刊名：AAPS PharmSciTech
• 出版年：2012
• 出版时间：September 2012
• 年：2012
• 卷：13
• 期：3
• 页码：875-882
• 全文大小：401KB
• 参考文献：1. European Directorate for the Quality of Medicines and Healthcare (EDQM): European Pharmacopeia 6(8). Chapter 2.9.18. Preparations for inhalations: aerodynamic assessment of fine particles. Strasbourg: Council of Europe; 2010.
  2. US Pharmacopeial Convention. United States Pharmacopeia; USP 33-NF 28; chapter 601—physical tests and determinations: aerosols. United States Pharmacopeia, Rockville, MD, USA; 2010.
  3. Mitchell JP, Nagel MW. Cascade impactors for the size characterization of aerosols from medical inhalers: their uses and limitations. J Aerosol Med. 2003;16(4):341-7. p://dx.doi.org/10.1089/089426803772455622">CrossRef
  4. Copley M, Smurthwaite M, Roberts DL, Mitchell JP. 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. 2005;18(3):364-. p://dx.doi.org/10.1089/jam.2005.18.364">CrossRef
  5. Mitchell JP, Newman S, Chan H-K. / In vitro and / in vivo aspects of cascade impactor tests and inhaler performance: a review. AAPS PharmSciTechnol. 2007;8(4):237-8. p://dx.doi.org/10.1208/pt0804110">CrossRef
  6. Dunbar C, Mitchell J. Analysis of cascade impactor mass distributions. J Aerosol Med. 2005;18(4):439-1. p://dx.doi.org/10.1089/jam.2005.18.439">CrossRef
  7. Marple VA, Olson BA, Santhanakrishnan K, Mitchell JP, Murray S, Hudson-Curtis B. Next generation pharmaceutical impactor. Part II: calibration. J Aerosol Med. 2003;16:301-4. p://dx.doi.org/10.1089/089426803769017668">CrossRef
  8. Nichols SC. Calibration and mensuration issues for the standard and modified impactor. Pharmeuropa. 2000;12(4):585.
  9. Mitchell JP, Costa PA, Waters S. An assessment of an Andersen mark-II cascade impactor. J Aerosol Sci. 1987;19:213-1. p://dx.doi.org/10.1016/0021-8502(88)90224-8">CrossRef
  10. Beron K, Grabek CE, Jung JA, Shelton CM. Flow rate ramp profile effects on the emitted dose from dry powder inhalers. In: Drug delivery to the lungs, 19. Edinburgh: The Aerosol Society; 2008. p. 61-.
  11. Marple VA, Roberts DL, Romay FJ, Miller NC, Truman KG, Van Oort M, / et al. Next generation pharmaceutical impactor. Part 1: design. J Aerosol Med. 2003;16:283-9. p://dx.doi.org/10.1089/089426803769017659">CrossRef
  12. Bird RB, Stewart WE, Lightfoot EN. Transport phenomena. New York: Wiley; 1960. p. 126.
  13. Roberts DL, Chiruta M. Transient impactor behavior during the testing of dry-powder inhalers via compendial methods. In: Drug delivery to the lungs, 18. Edinburgh: The Aerosol Society; 2007. p. 202-.
  
• 作者单位：Hlack Mohammed (1)
  Daryl L. Roberts (2)
  Mark Copley (3)
  Mark Hammond (4)
  Steven C. Nichols (5)
  Jolyon P. Mitchell (6)
  
  1. GSK plc, Park Road, Ware, Hertfordshire, SG12 ODP, UK
  2. MSP Corp., Shoreview, MN, 55126, USA
  3. Copley Scientific Ltd, Nottingham, NG4 2JY, UK
  4. Melbourn Scientific Ltd, Melbourn, SG8 6DN, UK
  5. OINDP Consultancy, Smallwood, Cheshire, CW11 2UN, UK
  6. Trudell Medical International, 725 Third Street, London, ON, Canada, N5V 5G4
  

文摘

Current pharmacopeial methods for testing dry powder inhalers (DPIs) require that 4.0?L be drawn through the inhaler to quantify aerodynamic particle size distribution of “inhaled-particles. This volume comfortably exceeds the internal dead volume of the Andersen eight-stage cascade impactor (ACI) and Next Generation pharmaceutical Impactor (NGI) as designated multistage cascade impactors. Two DPIs, the second (DPI-B) having similar resistance than the first (DPI-A) were used to evaluate ACI and NGI performance at 60?L/min following the methodology described in the European and United States Pharmacopeias. At sampling times ??s (equivalent to volumes ?.0?L), both impactors provided consistent measures of therapeutically important fine particle mass (FPM) from both DPIs, independent of sample duration. At shorter sample times, FPM decreased substantially with the NGI, indicative of incomplete aerosol bolus transfer through the system whose dead space was 2.025?L. However, the ACI provided consistent measures of both variables across the range of sampled volumes evaluated, even when this volume was less than 50% of its internal dead space of 1.155?L. Such behavior may be indicative of maldistribution of the flow profile from the relatively narrow exit of the induction port to the uppermost stage of the impactor at start-up. An explanation of the ACI anomalous behavior from first principles requires resolution of the rapidly changing unsteady flow and pressure conditions at start up, and is the subject of ongoing research by the European Pharmaceutical Aerosol Group. Meanwhile, these experimental findings are provided to advocate a prudent approach by retaining the current pharmacopeial methodology.