Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Pharm. 2010 Aug 16;395(1-2):205-14. doi: 10.1016/j.ijpharm.2010.05.043. Epub 2010 Jun 4.
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.
本工作旨在开发具有最佳物理和空气动力学特性的高阿奇霉素载药吸入粉末，并在大鼠体内进行测试。采用五水平三因素中心组合旋转设计进行实验。在选定的喷雾干燥条件下，获得了具有更好流动性、空气动力学直径为 3.82 微米和体外沉积率为 51%的优化粉末。该粉末的载药量高（59.2%），满足高载药量的要求。进一步在大鼠体内研究中对优化粉末进行了考察。对每只大鼠同时进行肺微透析和血微透析。气管内途径与静脉注射的 AUC（ELF）比值为 161.6，而绝对生物利用度仅为 43.5%，气管内途径的药物靶向指数为 486.2。结果表明，阿奇霉素干粉吸入剂（DPI）可有效、高效地递送至特定靶部位，并实现高局部浓度。总之，AZI DPI 提供了一种有吸引力的替代方案，能够将高浓度抗生素直接递送至选定的靶部位，同时最小化全身生物利用度和副作用。
