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Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin

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Abstract

Purpose

Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability.

Methods

The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels – 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy.

Results

Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin.

Conclusions

The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be the result of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.

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Acknowledgements

This publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institute of Health under Award Numbers R01AI132681 and R01AI146160. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. J.L. is an Australian National Health and Medical Research Council (NHMRC) Principal Research Fellow (APP1157909).

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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, IN, 47907, USA

    Vaibhav Pathak, Heejun Park, Sonal V. Bhujbal, Maizbha Uddin Ahmed & Qi Tony Zhou

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

    Dmitry Zemlyanov

  3. Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, 3800, Australia

    Mohammad A. K. Azad & Jian Li

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Correspondence to Qi Tony Zhou.

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Conflict of Interest

MUA, MAKA, JL and QTZ are inventors of PCT/US2021/030393. JL received speaking honoraria from Genentech, Healcare, CTTQ, MedCom, Jiayou Medicine, and Aosaikang.

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Pathak, V., Park, H., Zemlyanov, D. et al. Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin. Pharm Res 39, 2781–2799 (2022). https://doi.org/10.1007/s11095-022-03344-5

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