Improved Quality Control Metrics for Cascade Impaction Measurements of Orally Inhaled Drug Products (OIPs)

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• 作者：Terrence P. Tougas (1)
  David Christopher (2)
  Jolyon P. Mitchell (3)
  Helen Strickland (4)
  Bruce Wyka (5)
  Mike Van Oort (6)
  Svetlana Lyapustina (7)
  
• 关键词：aerosol ; AIM concept ; cascade impactor ; inhaler ; QC
• 刊名：AAPS PharmSciTech
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：10
• 期：4
• 页码：1276-1285
• 全文大小：331KB
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  6. Adams WP, Christopher D, Lee DS, Morgan B, Pan Z, Singh GJP, Tsong Y, Lyapustina S. Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 1: background for a statistical method. AAPS PharmSciTech. 2007;8(1):Article 4. doi:pan class="a-plus-plus non-url-ref">10.1208/pt0801004 . p://www.aapspharmscitech.org/default/issueView.asp?vol=08&issue=01" class="a-plus-plus">http://www.aapspharmscitech.org/default/issueView.asp?vol=08&issue=01 or p://www.aapspharmscitech.org/view.asp?art=pt0801004" class="a-plus-plus">http://www.aapspharmscitech.org/view.asp?art=pt0801004. Accessed 4 Aug 2009.
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  9. Christopher D, Curry P, Doub W, Furnkranz K, Lavery M, Lin K, / et al. Considerations for the development and practice of cascade impaction testing including a mass balance failure investigation tree. J Aerosol Med. 2003;16(3):235-7. p://dx.doi.org/10.1089/089426803769017604">CrossRef
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  15. Christopher D, Dey M, Lyapustina S, Mitchell J, Stein S, Tougas T, Van Oort M. Alternative approaches for MMAD determination. Poster presented at the IPAC-RS Conference 2008. p://ipacrs.com/PDFs/Posters/Alternative%20MMAD.pdf" class="a-plus-plus">http://ipacrs.com/PDFs/Posters/Alternative%20MMAD.pdf. Accessed 4 Aug 2009.
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  17. Kamiya A, Sakagami M, Hindle M, Byron PR. Aerodynamic sizing of metered dose inhalers: an evaluation of the Andersen and next generation pharmaceutical impactors and their USP methods. J Pharm Sci. 2004;93(7):1828-7. p://dx.doi.org/10.1002/jps.20091">CrossRef
  18. Mitchell JP, Nagel MW, Wiersema KJ, Doyle CC. 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. AAPS PharmSciTech. 2003;4(4):article 54.
  19. Mitchell JP, Nagel MW, Avvakoumova V, MacKay H, Ali R. The abbreviated impactor measurement (AIM) concept: part I—influence of particle bounce and re-entrainment—evaluation with a “dry-pressurized metered dose inhaler (pMDI)-based formulation. AAPS PharmSciTech. 2009;10(1):243-1. p://dx.doi.org/10.1208/s12249-009-9202-9">CrossRef
  20. Mitchell JP, Nagel MW, Avvakoumova V, MacKay H, Ali R. 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. 2009;10(1):252-. p://dx.doi.org/10.1208/s12249-009-9201-x">CrossRef
  
• 作者单位：Terrence P. Tougas (1)
  David Christopher (2)
  Jolyon P. Mitchell (3)
  Helen Strickland (4)
  Bruce Wyka (5)
  Mike Van Oort (6)
  Svetlana Lyapustina (7)
  
  1. CMC Development, Boehringer Ingelheim, Ridgefield, Connecticut, USA
  2. Statistics, Schering-Plough Research Institute, Kenilworth, New Jersey, USA
  3. Trudell Medical Group, London, Ontario, Canada
  4. Statistics, GlaxoSmithKline, Zebulon, North Carolina, USA
  5. SpiraPharma Consulting, Lincoln Park, New Jersey, USA
  6. Inhaled Product Development, GlaxoSmithKline, Research Triangle Park, North Carolina, USA
  7. Pharmaceutical Practice Group, Drinker Biddle & Reath LLP, 1500 K Street, N.W., Suite 1100, Washington, DC, 20005-1208, USA
  

文摘

This study of aerodynamic mass-weighted particle size distribution (APSD) data from orally inhaled products (OIPs) investigated whether a set of simpler (than currently used) metrics may be adequate to detect changes in APSD for quality control (QC) purposes. A range of OIPs was examined, and correlations between mass median aerodynamic diameter and the ratio of large particle mass (LPM) to small particle mass (SPM) were calculated. For an Andersen cascade impactor, the LPM combines the mass associated with particle sizes from impactor stage 1 to a product-specific boundary size; SPM combines the mass of particles from that boundary through to terminal filter. The LPM–SPM boundary should be chosen during development based on the full-resolution impactor results so as to maximize the sensitivity of the LPM/SPM ratio to meaningful changes in quality. The LPM/SPM ratio along with the impactor-sized mass (ISM) are by themselves sufficient to detect changes in central tendency and area under the APSD curve, which are key in vitro quality attributes for OIPs. Compared to stage groupings, this two-metric approach provides better intrinsic precision, in part due to having adequate mass and consequently better ability to detect changes in APSD and ISM, suggesting that this approach should be a preferred QC tool. Another advantage is the possibility to obtain these metrics from the abbreviated impactor measurements (AIM) rather than from full-resolution multistage impactors. Although the boundary is product specific, the testing could be accomplished with a basic AIM system which can meet the needs of most or all OIPs.