Issue link: https://www.e-digitaleditions.com/i/1518209
26 April 2024 Inhalation maceutical Impactor. Part 1: Design. J. Aerosol Med. 2003; 16: 283-299. 3. Lostritto R. Quality by design, risk management, and new review paradigms for inhalation drug prod- ucts. Respiratory Drug Delivery 2005; pp. 105-113. https://www.rddonline.com/rdd/rdd.php?sid=103. 4. US Pharmacopeial Convention: United States Pharmacopeia/National Formulary 2023, Chapter <601> Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers. Rockville, MD, US, 2023. https://www.uspnf.com/. 5. European Pharmacopoeia Monograph 2.9.18. European Directorate for Quality in Medicines (EDQM), Issue 11.3 2024. Strasbourg, France. https://pheur.edqm.eu/home. 6. Tougas TP, Mitchell JP, Lyapustina SL. Good cas- cade impactor practices, AIM and EDA for orally inhaled products. Springer, New York, NY: 2013. 7. Stenhouse JIT. Fibrous filtration. In: Physical and chemical properties of aerosols. Ed. I. Colbeck. Blackie Academic & Professional. 1998. pp. 249-279. 8. Tsai PP, Schreuder-Gibson H, Gibson P. Differ- ent electrostatic methods for making electret filters. J. Electrost. 2002; 54(3-4): 333-341. 9. Jung S, Kim J, Advanced design of fiber-based particulate filters: Materials, morphology and con- struction of fibrous assembly. Polymers 2020; 12: article 1714. 10. Mitchell JP, Nagel MW, Doyle C, Ali RS, Avvak- oumova V, Christopher D, Quiroz J, Strickland H, Tougas T, Lyapustina S. Relative precision of inhaler aerodynamic particle size distribution (APSD) met- rics by full resolution and abbreviated Andersen Cas- cade Impactors (ACIs): Part 1. AAPS PharmSciTech. 2010; 11(2): 843-851. 11. Versteeg HK, Roberts DL, Cooper A, Chambers F, Copley M, Mitchell JP. A cross-industry assessment of the flow rate-elapsed time profiles of test equip- ment typically used for dry-powder inhaler (DPI) testing: Part 2—Analysis of transient air flow in the testing of DPIs with compendial cascade impactors. Aerosol Sci. Technol. 2020; 54(12): 1448-1470. 12. Roberts DL. Pressure drop characteristics of the reduced NGI™ configuration with several common glass-fiber filters. J. Aerosol Med. Pulmon. Drug Deliv. 2023; 36(2): 82-88. Daryl L. Roberts, PhD, (corresponding author) is President of Applied Particle Principles, LLC, 17347 Westham Estates Court, Hamilton, VA, 20158, US, Tel.: +1 612 845-3293, droberts@particleprinciples. com, www.particleprinciples.com. Jolyon P. Mitchell, PhD, is President of Jolyon Mitchell Inhaler Consulting Services, Inc., London, Ontario, Canada. Tel.: +1 519 472-5364, mitchelljolyon@gmail.com. through the sampling apparatus. Users should also be aware that similar considerations would apply for the determination of aerodynamic particle size dis- tribution (APSD) of particles generated by DPIs if a back-up filter is used as part of the impactor appa- ratus (including the situation where such a filter is used with an NGI, either in conjunction with the micro-orifice collector or as its replacement). We found surprisingly large variations in resistance for ostensibly similar filter types, based on their label- ling. Because this information is absent from the technical specifications and brochures for these filter products, we recommend that users determine filter resistance for themselves. is determination can be accomplished with a simple test system like the one depicted in Figure 1, as part of the apparatus quali- fication process and can be repeated as needed if the supplier of the filter is changed or a filter product change is deemed necessary. We have described a relatively simple apparatus for validating filter media. However, as an unintended consequence of this investigation and a previous study by Roberts [12], the importance of the filter support media has become apparent. Consequently, validation of the complete filter assembly clearly is needed for confident quality control in these filter- containing test systems. In this regard, we urge indus- trial users to generate and publish more data so that these characteristics of the typical pharmacopeial test equipment can move towards standardization. e quantitative effect of filter flow resistance on total dose or APSD will depend on detailed device characteristics. Future studies in our own laboratory or that of others will hopefully answer this question. Meanwhile, in the studies we have addressed here, the pressure drop values of various filters are not sim- ply different than each other; rather that difference is a significant fraction of the ambient pressure (e.g., 5% of a typical 100-kPa normal atmosphere). So in a world where users and regulators speak of multi- ple-percentage-level reproducibility requirements, and even the length of tubing used in DPI testing is in an advisable range in the USP [4] and PhEur [5], we believe that filter flow resistance variability is a far more significant parameter that should not be neglected as a source of data variability. If our early study, here, stimulates formal evaluations of the sig- nificance of this parameter by inhaler testing practi- tioners, we will have achieved our goal. References 1. Copley M. Variability in cascade impaction: Sources, impact and strategies for reduction. ONdrugDelivery Magazine. 2018; 92: 60-65. 2. Marple VA, Roberts DL, Romay FJ, Miller NC, Truman KG, Van Oort M, Olsson B, Holroyd MJ, Mitchell JP, Hochrainer D. Next Generation Phar-