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The Delivery of High-Dose Dry Powder Antibiotics by a Low-Cost Generic Inhaler

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Abstract

The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 μm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer® with the same configuration (single pin and one-third air inlet) that accommodates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5–2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer® inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections.

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Acknowledgments

Thaigarajan Parumasivam is a recipient of the Malaysian Government Scholarship. Sharon Leung is a research fellow supported by the University of Sydney. The authors wish to acknowledge the technical support of Australian Microscopy & Microanalysis Research Facility at the Australian Centre for Microscopy and Microanalysis, The University of Sydney. The work was supported by the Australian Research Council’s Discovery Project (DP150103953), the National Health and Medical Research Council Centre of Research Excellence in Tuberculosis Control (APP1043225) and Project grant (APP104434) and the NSW Government Infrastructure Grant to the Centenary Institute.

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Authors and Affiliations

  1. Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia

    Thaigarajan Parumasivam, Sharon S. Y. Leung, Patricia Tang & Hak-Kim Chan

  2. R & D and Industrialization, Plastiape S.p.A., 23875, Osnago, Italy

    Citterio Mauro

  3. Tuberculosis Research Program, Centenary Institute, The University of Sydney, Sydney, NSW, 2006, Australia

    Warwick Britton

  4. Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia

    Warwick Britton

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  1. Thaigarajan Parumasivam
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  2. Sharon S. Y. Leung
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  4. Citterio Mauro
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Correspondence to Hak-Kim Chan.

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Parumasivam, T., Leung, S.S.Y., Tang, P. et al. The Delivery of High-Dose Dry Powder Antibiotics by a Low-Cost Generic Inhaler. AAPS J 19, 191–202 (2017). https://doi.org/10.1208/s12248-016-9988-9

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  • DOI: https://doi.org/10.1208/s12248-016-9988-9

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