High azithromycin loading powders for inhalation and their in vivo evaluation in rats.

The aim of the present work is to develop high azithromycin loading powders for inhalation with optimal physical and aerodynamic properties, and to test their in vivo potential in rats. A five-level three-factorial central composite rotatable design was used for conducting the experiments. The optimized powder, which had a better flowability, an aerodynamic diameter of 3.82 microm and an in vitro deposition of 51%, was obtained under selected spray-drying conditions. The content of the powder was high (59.2%), which met the requirement for high drug loading. The optimized powder was further examined in the in vivo study in rats. Lung microdialysis and blood microdialysis were simultaneously performed on each rat. The ratio of the AUC(ELF) value between the intratracheal route and intravenous injection was 161.6, whereas the absolute bioavailability was only 43.5%, and the drug targeting index of the intratracheal route was 486.2. The results showed that azithromycin dry powder inhalers (DPI) could be effectively and efficiently delivered to a specific target site and achieve a high local concentration. In conclusion, AZI DPI offers an attractive alternative that is able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the systemic bioavailability and side effects. Copyright (c) 2010 Elsevier B.V. All rights reserved.