• Mohammad A M Momin, Shubhra Sinha, Ian G Tucker, Colin Doyle, and Shyamal C Das.
• New Zealand's National School of Pharmacy, University of Otago, 18 Frederick Street, Dunedin 9054, New Zealand.
• Int J Pharm. 2017 Aug 7; 528 (1-2): 107-117.

BackgroundKanamycin, an injectable agent, is currently used to treat drug-resistant tuberculosis (TB). Parenteral kanamycin causes high systemic toxicity which could be avoided by direct delivery to the lungs. This study focused on producing a highly aerosolizable dry-powder of hygroscopic kanamycin by spray-drying with l-leucine.MethodsKanamycin powders were prepared with different concentrations (0, 5, 10, 15 and 20% w/w) of l-leucine using the Buchi B-290 Mini Spray-Dryer. In vitro aerosolization efficiency, particle size, morphology, crystallinity, surface composition, drug-excipient interaction and moisture content of the powders were characterized by a Next Generation Impactor (NGI), laser diffraction, scanning electron microscopy, X-ray diffractometry, XPS, ATR-FTIR and thermogravimetric analysis. The physicochemical and aerosolization stability of the powders were investigated after one-month storage at 25±2°C/15% RH and 25±2°C/75% RH. The cytotoxicity on Calu-3 and A549 cells of the kanamycin powders was evaluated by MTT assay.ResultsThe spray-dried powder particles were in the inhalable size range (<6.1μm). The powders with l-leucine were wrinkled in shape, amorphous in nature and had low moisture content (<5.0%). Kanamycin with 5% (w/w) of l-leucine showed the best aerosolization efficiency of 73.0±2.5%. The powders remained stable during storage at 25±2°C/15% RH and tolerated by respiratory cell lines.Conclusionl-leucine improved the aerosolization of kanamycin by surface modification, which may be helpful for the effective treatment of drug-resistant tuberculosis.Copyright © 2017 Elsevier B.V. All rights reserved.

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