Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 102, Issue 5, Pages 1578-1587Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.23508
Keywords
colistin; azithromycin; colloid; controlled release; liposome; encapsulation; antiinfectives
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Remote loading of azithromycin into liposomes, and subsequent release behavior in the presence of colistin, has been investigated with a view to understand the potential of liposomes to enable the coformulation of these two antibiotics for application in inhalation therapy. Azithromycin was successfully encapsulated into liposomes by remote loading (encapsulation efficiency > 98%). Slow release of azithromycin was achieved in the presence of cholesterol in a concentration-dependent manner, with a 4:1 mol ratio of phospholipidcholesterol releasing 22% azithromycin in 24 h, whereas a 2:1 mol ratio released only 4.9% of azithromycin in 24 h. Addition of colistin to the formulation with increasing concentration did not change the loading behavior, but accelerated drug release, increasing the percentage of released azithromycin from 4.9% to 30% over 24 h. The permeabilizing ability of colistin on liposomes is consistent with its permeabilizing effect on bacterial cells. This behavior opens opportunities to tailor the release rate of drugs coformulated with colistin using liposomes as the carrier. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:15781587, 2013
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