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18 April 2018 Inhalation References 1. Roberts, D. L., F. J. Romay, "Relationship of Stage Mensura- tion Data to the Performance of New and Used Cascade Impac- tors," J. Aerosol Med., 18 (4), 396-413 (2005). 2. Roberts, D. L., J. P. Mitchell, "Suitability of Used Impac- tors—Why the 'Effective Diameter' Criterion Needs the 'Jet- to-Plate' Criterion to Assure Measurement Capability in a Good Cascade Impactor Practice (GCIP) Environment," Drug Delivery to the Lungs 2017, e Aerosol Society, Edinburgh, UK, December 6-8, 2017, pp. 306-310. 3. Marple, V. A., "A Fundamental Study of Inertial Impactors," PhD esis, Mechanical Engineering Department, University of Minnesota (1970). 4. Fang, C. P., V. A. Marple, K. L. Rubow, "Influence of Cross- Flow on Particle Collection Characteristics of Multi-Nozzle Impactors," J. Aero. Sci., 22, 403-415 (1991). 5. Marple, V. A., K. L. Rubow, S. M. Behm, "A Microorifice Uniform Deposit Impactor (MOUDI): Description, Calibra- tion, and Use," Aero. Sci. Tech., 14, 434-446 (1991). 6. Marple, V. A., B. A. Olson, N. C. Miller, "A Low-Loss Cas- cade Impactor with Stage Collection Cups: Calibration and Pharmaceutical Inhaler Applications," Aero. Sci. Tech., 22, 124-134 (1995). 7. Marple, V. A., K. Willeke, "Impactor Design," Atmos. Env., 10, 891-896 (1976). 8. Marple, V. A., B. A. Olson, "Sampling and Measurement Using Inertial, Gravitational, Centrifugal, and ermal Tech- niques," Chapter 8 of Aerosol Measurement: Principles, Tech- niques, and Applications, Kulkami, P., P. A. Baron, K. Willeke (eds), ird Edition, Wiley & Sons, New Jersey, US, pp. 129- 151, (2011). 9. Mitchell, J. P., D. L. Roberts, "Current Approaches to APSD Measurements of OIPs based on Inertial Impaction," Chapter 2 of Good Cascade Impactor Practices, Tougas, T. P., J. P. Mitch- ell, S. A. Lyapustina (eds), Springer, NY, US, pp. 15-55, (2013). 10. United States Pharmacopiea, 24 (2000) "Aerosols, Metered Dose Inhalers and Dry Powder Inhalers," General Chapter <601>. United States Pharmacopeial Convention, Rockville, MD, pp. 1895-1912. 11. Kadrichu, N., N. Rao, G. Sluggett, B. Fong, G. Jones, T. Perrone, S. Seshadri, P. Shao, G. Williams, J. Zhang, D. Ben- nett, "Sensitivity of Andersen Cascade Impactor Response to Stage Nozzle Dimensions," Respiratory Drug Delivery IX, RDD Online, Palm Springs, CA, April 25-29, 2004, pp. 561- 563. 12. Roberts, D. L., "eory of Multi-Nozzle Impactor Stages and the Interpretation of Stage Mensuration Data," Aerosol Sci. Tech., 43, 1119-1129 (2009). 13. Roberts, D. L., J. P. Mitchell, "e Effect of Non ideal Cas- cade Impactor Stage Collection Efficiency Curves on the Inter- pretation of the Size of Inhaler-Generated Aerosols," AAPS Pharm. Sci. Tech., 14 (2), 497-510 (June 2013). Daryl L. Roberts, PhD is President of Applied Particle Principles, LLC, 17347 Westham Estates Court, Hamil- ton, VA, 20158, US, Tel.: +1 612 845-3293, droberts@ particleprinciples.com, www.particleprinciples.com. Christopher M. Shelton, MS is Associate Director at West- Ward Pharmaceuticals, Columbus, OH, US, cshelton@ west-ward.com. newly manufactured stage]. As observed in Table 2, stages 4 through 7 each contain several nozzles with diameters that are more than 0.010 mm from the nomi- nal value, which is outside of the range specified for a newly manufactured impactor. Evaluation of D eff alone would not indicate whether one or more of these noz- zles is outside of the dimensional specification for S/W. For Stage 4, which has less than 100 nozzles on the stage, the presence of a single nozzle not meeting the S/W specification would not be detectable with D eff , but may be detectable by comparison of the area-mean and area-median diameters, where a difference of greater than 0.003 mm is a clear indication of an atypical nozzle on the stage. e presence of an atypical nozzle diameter for Stage 4 has a high chance to be detected by comparison of the area-mean and area-median diameters, but stages with more nozzles make this comparison less reliable. For example, in the case of Stage 7, if the five nozzles in Table 2 with diameters smaller than 0.010 mm from the nominal value were completely occluded (diameter of "0"), then the area-mean, area-median and effective diameters calculated for the stage (Table 1) would be unchanged! Calculation of the S/W ratio for each noz- zle using all measured diameters and the nominal S value shows that no atypical nozzles are present on any stage (Table 3). e D eff metric allows for the conclusion of acceptability of a used impactor to be made when the assumption that all nozzles on the stage are functioning within the design criteria is met. However, as shown in the exam- ples above, the descriptive statistics of the mensuration results used to calculate D eff are not sufficient to prove that the condition for all individual nozzles has been met. erefore, evaluation of the calculated S/W values using the measured diameters obtained during mensu- ration provides a simple and necessary test for whether the aerodynamics of the impactor stages are within that allowed for a new impactor. In this way, the test of the S/W criteria avoids a Type II error that could be made if the decision were based on the D eff criterion alone. Conclusions Impactors operate on known aerodynamic principles. Consequently, the criterion for continued use must be that the aerodynamics of the used impactor are in the same range as those of allowed for a new impactor. Proper aerodynamics are obtained when both the D eff and the S/W criteria are met. Both of these tests can be made by quantitative measurement of the nozzle diameters (stage mensuration). erefore "stage men- suration" data are sufficient for performing the D eff test and the S/W test. Together these tests will help users avoid Type I errors (via the D eff test) and Type II errors (via the S/W test), leading to high confidence that appropriate decisions are being made for keeping or rejecting used impactors.