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Is “Slow Inhalation” Always Suitable for Pressurized Metered Dose Inhaler?

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Abstract

To achieve adequate inhalation therapy, a proper inhalation technique is needed in clinical practice. However, there is limited information on proper inhalation flow patterns of commercial inhalers. Here, we quantitatively estimated airway deposition of two commercial pressurized metered dose inhalers (pMDIs) to determine their optimal inhalation patterns. Sultanol® inhaler (drug particles suspended in a propellant, suspension-pMDI) and QVAR™ (drug dissolved in a propellant with ethanol, solution-pMDI) were used as model pMDIs. Aerodynamic properties of the two pMDIs were determined using an Andersen cascade impactor with human inhalation flow simulator developed by our laboratory. As indices of peripheral-airway drug deposition, fine particle fractions (FPFPA) at different inhalation flow rates were calculated. The time-dependent particle diameters of sprayed drug particles were determined by laser diffraction. On aerodynamic testing, FPFPA of suspension-pMDI significantly decreased depending on the increasing inhalation flow rate, while solution-pMDI achieved higher and constant FPFPA in the range of the tested inhalation flow rates. The particle diameter of solution-pMDI markedly decreased from 5 to 3 μm in a time-dependent manner. Conversely, that of suspension-pMDI remained at 4 μm during the spraying time. Although “slow inhalation” is recommended for pMDIs, airway drug deposition via solution-pMDI (extra-fine particles) is independent of patients’ inhalation flow pattern. Clinical studies should be performed to validate instruction for use of pMDIs for each inhaler for the optimization of inhalation therapy.

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Acknowledgments

We wish to express thanks for the technical help given by Malvern Panalytical Ltd. for measurement of particle diameters.

Funding

This work was supported by Nakatomi Foundation and JSPS KAKENHI Grant Number JP17K15504.

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Authors and Affiliations

  1. Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi, 468-8503, Japan

    Daiki Hira, Tomoyuki Okuda, Ayano Mizutani, Nao Tomida, Megumi Mizuno & Hirokazu Okamoto

  2. College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga, 525-8577, Japan

    Daiki Hira, Satoshi Ueshima, Mikio Kakumoto & Tomonobu Okano

  3. Department of Pharmacy, Shiga University of Medical Science Hospital, Seta Tsukinowa-Cho, Otsu, Shiga, 520-2192, Japan

    Daiki Hira

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  1. Daiki Hira
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  2. Tomoyuki Okuda
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  3. Ayano Mizutani
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  4. Nao Tomida
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  5. Megumi Mizuno
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  8. Tomonobu Okano
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  9. Hirokazu Okamoto
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Correspondence to Hirokazu Okamoto.

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Hira, D., Okuda, T., Mizutani, A. et al. Is “Slow Inhalation” Always Suitable for Pressurized Metered Dose Inhaler?. AAPS PharmSciTech 21, 53 (2020). https://doi.org/10.1208/s12249-019-1610-x

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