期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 105, 期 3, 页码 1156-1163出版社
WILEY
DOI: 10.1016/S0022-3549(15)00189-6
关键词
dry powder inhaler; respiratory infection; antibiotics; jet milling; spray drying; surface energy; inverse gas chromatography; self-assembly; colistin
资金
- Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI098771, AI111965]
This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without t-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of t-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without L-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance. (C) 2016 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
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