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Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation

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Abstract

Purpose

Dissolution behavior of dry powder inhaler (DPI) antibiotic formulations in the airways may affect their efficacy especially for poorly-soluble antibiotics such as azithromycin. The main objective of this study was to understand the effects of surface composition on the dissolution of spray dried azithromycin powders by itself and in combination with colistin.

Methods

Composite formulations of azithromycin (a poorly water-soluble molecule) and colistin (a water-soluble molecule) were produced by spray drying. The resultant formulations were characterized for particle size, morphology, surface composition, solid-state properties, solubility and dissolution.

Results

The results demonstrate that surfaces composition has critical impacts on the dissolution of composite formulations. Colistin was shown to increase the solubility of azithromycin. For composite formulations with no surface colistin, azithromycin released at a similar dissolution rate as the spray-dried azithromycin alone. An increase in surface colistin concentration was shown to accelerate the dissolution of azithromycin. The dissolution of colistin from the composite formulations was significantly slower than the spray-dried pure colistin. In addition, FTIR spectrum showed intermolecular interactions between azithromycin and colistin in the composite formulations, which could contribute to the enhanced solubility and dissolution of azithromycin.

Conclusions

Our study provides fundamental understanding of the effects of surface concentration of colistin on azithromycin dissolution of co-spray-dried composite powder formulations.

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ACKNOWLEDGMENTS AND DISCLOSURES

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI132681. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Jian Li is an Australian NHMRC Senior Research Fellow. The authors are grateful for the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Future Industries Institute, University of South Australia. The authors are thankful for access to FTIR in Tonglei Li’s lab. Kind donations of RS01 DPI device from Plastiape S.p.A. and HPMC capsules from Qualicaps, Inc. are acknowledged.

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Author notes

  1. Sharad Mangal and Rongkun Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Sharad Mangal, Rongkun Xu, Heejun Park, Nivedita Shetty & Qi Tony Zhou

  2. Birck Nanotechnology Center, Purdue University, 1205 West State Street, West Lafayette, Indiana, 47907, USA

    Dmitry Zemlyanov

  3. Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, 3800, Australia

    Yu-Wei Lin & Jian Li

  4. Drug Delivery, Dynamics & Deposition, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    David Morton

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

    Hak-Kim Chan

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  1. Sharad Mangal
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  2. Rongkun Xu
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Corresponding author

Correspondence to Qi Tony Zhou.

Appendix

Appendix

Fig. 10
figure 10

Dissolution rate of colistin and azithromycin (in nm) measured by the Franz diffusion method (a) or beaker method (b).

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Table V MMAD and GSD of Spray Dried Formulations
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Mangal, S., Xu, R., Park, H. et al. Understanding the Impacts of Surface Compositions on the In-Vitro Dissolution and Aerosolization of Co-Spray-Dried Composite Powder Formulations for Inhalation. Pharm Res 36, 6 (2019). https://doi.org/10.1007/s11095-018-2527-x

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