Relative Precision of Inhaler Aerodynamic Particle Size Distribution (APSD) Metrics by Full Resolution and Abbreviated Andersen Cascade Impactors (ACIs): Part 1
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- 作者：Jolyon P. Mitchell (1)
Mark W. Nagel (1)
Cathy C. Doyle (1)
Rubina S. Ali (1)
Valentina I. Avvakoumova (1)
J. David Christopher (2)
Jorge Quiroz (2)
Helen Strickland (3)
Terrence Tougas (4)
Svetlana Lyapustina (5) - 关键词：AIM ; APSD ; impactor ; inhaler ; simplified
- 刊名：AAPS PharmSciTech
- 出版年：2010
- 出版时间：June 2010
- 年：2010
- 卷：11
- 期：2
- 页码：843-851
- 全文大小：425KB
- 参考文献：1. Mitchell JP, Nagel MW. Cascade impactors for the size characterization of aerosols from medical inhalers: their uses and limitations. J Aerosol Med. 2003;16:341鈥?7. p://dx.doi.org/10.1089/089426803772455622">CrossRef
2. Bonam M, Christopher D, Cipolla D, Donovan B, Goodwin D, Holmes S, / et al. Minimizing variability of cascade impaction measurements in inhalers and nebulizers. AAPS PharmSciTech. 2008;9(2):404鈥?3. p://dx.doi.org/10.1208/s12249-008-9045-9">CrossRef
3. Van Oort M, Roberts W. Variable flow-variable stage-variable volume strategy for cascade impaction testing of inhalation aerosols. In: Dalby RN, Byron PR, Farr SJ, editors. Respiratory drug delivery鈥擵. Buffalo Grove: Interpharm Press Inc; 1996. p. 418鈥?1.
4. Christopher D, Curry P, Doub B, 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;16:235鈥?7. p://dx.doi.org/10.1089/089426803769017604">CrossRef
5. Mitchell JP. The role of aerosol measurement for aerodynamic particle size distribution (APSD) in a quality-by-design (QbD) environment. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, Young PM, editors. Respiratory drug delivery 2008. River Grove: Davis Healthcare International Publishing LLC; 2008. p. 779鈥?3.
6. Mitchell JP. 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. p://www.ipacrs.com/ipac2008.html" class="a-plus-plus">http://www.ipacrs.com/ipac2008.html. Accessed 10 Sept 2009.
7. Tougas TP, Christopher D, Mitchell JP, Strickland H, Wyka B, Van Oort M, / et al. Improved quality control metrics for cascade impaction measurements of orally inhaled drug products (OIPs). AAPS PharmSciTech. 2009;10(4):1276鈥?5. doi:
8. Mitchell JP, Nagel MW, Avvakoumova V, MacKay H, Ali R. The abbreviated impactor measurement (AIM) concept: part 1鈥攊nfluence of particle bounce and re-entrainment鈥攅valuation with a 鈥渄ry鈥?pressurized metered dose inhaler (pMDI)-based formulation. AAPS PharmSciTech. 2009;10(1):243鈥?1. p://dx.doi.org/10.1208/s12249-009-9202-9">CrossRef
9. Mitchell JP, Nagel MW, Avvakoumova V, MacKay H, Ali R. The abbreviated impactor measurement (AIM) concept: part 2鈥攊nfluence of evaporation of a volatile component鈥攅valuation with a 鈥渄roplet producing鈥?pressurized metered dose inhaler (pMDI)-based formulation containing ethanol as co-solvent. AAPS PharmSciTech. 2009;10(1):252鈥?. p://dx.doi.org/10.1208/s12249-009-9201-x">CrossRef
10. USP33-NF28. Chapter <601> Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers. US Pharmacopeial Convention, Rockville, MD, USA. 2009.
11. European Pharmacopeia 6.03. Monograph 2.9.18. Preparations for inhalations: aerodynamic assessment of fine particles. European directorate for the quality of medicines (EDQM), Council of Europe, 67075 Strasbourg, France. 2009.
12. Dolovich MB, Mitchell JP. Canadian Standards Association standard CAN/CSA/Z264.1-02:2002: a new voluntary standard for spacers and holding chambers used with pressurized metered-dose inhalers. Can Respir J. 2004;11(7):489鈥?5.
13. Trudell Medical International, analytical laboratory procedure (ALP) 025: HPLC drug assay鈥攎ethod for Albuterol, Rev.G, July 2009.
14. Marple VA, Olson BA, Miller NC. The role of inertial collectors in evaluating pharmaceutical aerosol delivery systems. J Aerosol Med. 1998;11(S1):139鈥?3. - 作者单位：Jolyon P. Mitchell (1)
Mark W. Nagel (1)
Cathy C. Doyle (1)
Rubina S. Ali (1)
Valentina I. Avvakoumova (1)
J. David Christopher (2)
Jorge Quiroz (2)
Helen Strickland (3)
Terrence Tougas (4)
Svetlana Lyapustina (5)
1. Trudell Medical International, London, Ontario, Canada
2. Merck, Kenilworth, New Jersey, USA
3. GlaxoSmithKline Inc., Zebulon, North Carolina, USA
4. Boehringer Ingelheim Pharma Inc., Ridgefield, Connecticut, USA
5. Drinker, Biddle & Reath, 1500 K Street, NW, Suite 1100, Washington, District of Columbia, 20005-1209, USA
文摘
The purpose of this study was to compare relative precision of two different abbreviated impactor measurement (AIM) systems and a traditional multi-stage cascade impactor (CI). The experimental design was chosen to provide separate estimates of variability for each impactor type. Full-resolution CIs are useful for characterizing the aerosol aerodynamic particle size distribution of orally inhaled products during development but are too cumbersome, time-consuming, and resource-intensive for other applications, such as routine quality control (QC). This article presents a proof-of-concept experiment, where two AIM systems configured to provide metrics pertinent to QC (QC-system) and human respiratory tract (HRT-system) were evaluated using a hydrofluoroalkane-albuterol pressurized metered dose inhaler. The Andersen eight-stage CI (ACI) served as the benchmark apparatus. The statistical design allowed estimation of precision with each CI configuration. Apart from one source of systematic error affecting extra-fine particle fraction from the HRT-system, no other bias was detected with either abbreviated system. The observed bias was shown to be caused by particle bounce following the displacement of surfactant by the shear force of the airflow diverging above the collection plate of the second impaction stage. A procedure was subsequently developed that eliminated this source of error, as described in the second article of this series (submitted to AAPS PharmSciTech). Measurements obtained with both abbreviated impactors were very similar in precision to the ACI for all measures of in vitro performance evaluated. Such abbreviated impactors can therefore be substituted for the ACI in certain situations, such as inhaler QC or add-on device testing.