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The AAPS Journal

, Volume 18, Issue 5, pp 1213–1224 | Cite as

How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

  • Qi (Tony) Zhou
  • Zhi Hui Loh
  • Jiaqi Yu
  • Si-ping Sun
  • Thomas Gengenbach
  • John A. Denman
  • Jian Li
  • Hak-Kim ChanEmail author
Research Article

ABSTRACT

Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.

KEY WORDS

combination antibiotics dry powder inhaler hygroscopic amorphous particle moisture protection surface coating 

Notes

ACKNOWLEDGMENTS

The authors acknowledge the financial support from the Australian Research Council’s Discovery Project funding scheme (DP120102778) and the National Health and Medical Research Council’s (NHMRC) Project Grant funding scheme (APP1065046). Jian Li is an NHMRC Senior Research Fellow and is funded by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI098771 and AI111965). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The authors are grateful for the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Australian Centre for Microscopy and Microanalysis, The University of Sydney and the Future Industries Institute, University of South Australia.

Supplementary material

12248_2016_9934_MOESM1_ESM.docx (112 kb)
Supplement 1 Powder X-ray diffraction patterns of the spray-dried powder formulations. (DOCX 112 kb)
12248_2016_9934_MOESM2_ESM.docx (61 kb)
Supplement 2 C 1s high-resolution spectrum of composite sample (4Col:1AZI) measured by XPS and two model spectra of the pure compounds (Col, AZI) used for curve fitting. (DOCX 61 kb)
12248_2016_9934_MOESM3_ESM.docx (12 kb)
Supplement 3 Estimates of molar fractions of Col and AZI in composite formulations, based on curve fitting C 1s high-resolution spectra with model spectra. See text for details. (DOCX 11 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Qi (Tony) Zhou
    • 1
    • 2
  • Zhi Hui Loh
    • 3
  • Jiaqi Yu
    • 2
  • Si-ping Sun
    • 2
  • Thomas Gengenbach
    • 4
  • John A. Denman
    • 5
  • Jian Li
    • 6
  • Hak-Kim Chan
    • 2
    Email author
  1. 1.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA
  2. 2.Advanced Drug Delivery Group, Faculty of PharmacyThe University of SydneySydneyAustralia
  3. 3.Technical DevelopmentGlaxo Wellcome Manufacturing Pte LtdSingaporeSingapore
  4. 4.CSIRO ManufacturingClaytonAustralia
  5. 5.Future Industries InstituteUniversity of South AustraliaMawson LakesAustralia
  6. 6.Monash Biomedicine Discovery Institute and Department of MicrobiologyMonash UniversityMelbourneAustralia

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