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Comparison of Aerodynamic Particle Size Distribution Between a Next Generation Impactor and a Cascade Impactor at a Range of Flow Rates

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Abstract

Wide variation in respiratory flow rates between patients emphasizes the importance of evaluating the aerodynamic particle size distribution (APSD) of dry powder inhaler (DPI) using a multi-stage impactor at different flow rates. US Pharmacopeia recently listed modified configurations of the Andersen cascade impactor (ACI) and new sets of cut-off diameter specifications for the operation at flow rates of 60 and 90 L/min. The purpose of this study was to clarify the effect of these changes on the APSD of DPI products at varied flow rates. We obtained APSD profiles of four DPIs and device combinations, Relenza®-Diskhaler® (GlaxoSmithKline Co.), Seebri®-Breezhaler® (Novartis Pharma Co.), Pulmicort®-Turbuhaler® (Astrazeneca Co.), and Spiriva®-Handihaler® (Nippon Boehringer Ingelheim Co.) using Next Generation Impactors (NGIs) and ACIs at flow rates from 28.3 to 90 L/min to evaluate the difference in the use of previous and new sets of cut-off diameter specifications. Processing the data using the new specifications for ACI apparently reduced large differences in APSD obtained by NGI and ACI with the previous specifications at low and high flow rates in all the DPIs. Selecting the appropriate configuration of ACI corresponding to the flow rate provided comparable APSD profiles of Pulmicort®-Turbuhaler® to those using NGIs at varied flow rates. The results confirmed the relevance of the current US Pharmacopeia specifications for ACI analysis in obtaining APSD profiles of DPI products at wide flow rates.

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Acknowledgments

This work was partly supported by the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics of the Japan Agency for Medical Research and Development, AMED, and by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan.

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Authors and Affiliations

  1. Division of Drugs, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo, 158-8501, Japan

    Hiroyuki Yoshida, Akemi Kuwana, Hiroko Shibata, Ken-ichi Izutsu & Yukihiro Goda

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  1. Hiroyuki Yoshida
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  2. Akemi Kuwana
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  3. Hiroko Shibata
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  4. Ken-ichi Izutsu
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  5. Yukihiro Goda
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Correspondence to Hiroyuki Yoshida.

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Yoshida, H., Kuwana, A., Shibata, H. et al. Comparison of Aerodynamic Particle Size Distribution Between a Next Generation Impactor and a Cascade Impactor at a Range of Flow Rates. AAPS PharmSciTech 18, 646–653 (2017). https://doi.org/10.1208/s12249-016-0544-9

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  • DOI: https://doi.org/10.1208/s12249-016-0544-9

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