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Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

  • Research Paper
  • Theme: Formulation and Manufacturing of Solid Dosage Forms
  • Published:
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Abstract

Purpose

Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution.

Methods

The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated.

Results

The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations.

Conclusions

We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

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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. Qi (Tony) Zhou is a recipient of the Ralph W. and Grace M. Showalter Research Trust Award. 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. Kind donations of RS01 DPI device from Plastiape S.p.A. and HPMC capsules from Qualicaps, Inc. are acknowledged.

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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, Rui Guo & Qi (Tony) Zhou

  2. Teva Pharmaceuticals, 145 Brandywine Pkwy, West Chester, Pennsylvania, 19380, USA

    Haichen Nie

  3. Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China

    Rongkun Xu

  4. Future Industries Institute, University of South Australia, Mawson Lakes, SA, 5095, Australia

    Alex Cavallaro

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

    Dmitry Zemlyanov

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  1. Sharad Mangal
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Correspondence to Qi (Tony) Zhou.

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Guest Editors: Tony Zhou and Tonglei Li

Appendices

Appendix 1

Fig. 10
figure 10

Chemical structures of: (a) azithromycin; (b) L-leucine.

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Appendix 2

Fig. 11
figure 11

Deposition profiles of spray-dried formulations at various stages of MSLI after storage for 1 week at 55% RH (a) and 75% RH (b).

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Mangal, S., Nie, H., Xu, R. et al. Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation. Pharm Res 35, 28 (2018). https://doi.org/10.1007/s11095-017-2334-9

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