Development of an improved inhalable powder formulation of pirfenidone by spray-drying: in vitro characterization and pharmacokinetic profiling
Development of an improved inhalable powder formulation of pirfenidone by spray-drying: in vitro characterization and pharmacokinetic profiling
复制标题
通过喷雾干燥开发改进的吡非尼酮吸入粉末制剂：体外表征和药代动力学分析
DOI：
10.1007/s11095-016-1887-3
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发表时间：
2016
影响因子：
3.7
通讯作者：
Satomi Onoue
中科院分区：
文献类型：
--
作者：
2)Yoshiki Seto;Gen Suzuki;Sharon Shui Yee Leung;Hak-Kim Chan;Satomi Onoue
目的以前，吡非尼酮（PFD）的可吸入粉末（RP）制剂被开发用于降低光毒性风险;然而，PFD-RP在体外吸入性能方面表现出不可接受的。本研究旨在通过喷雾干燥法制备一种具有良好吸入特性的PFD新的RP系统。方法采用L-亮氨酸喷雾干燥法制备喷雾干燥PFD（SD/PFD），并在抗原致敏的气道炎症模型中评价其理化性质和疗效。SD/PFD的药代动力学研究也进行了后intrichelheal和口服administrationofPFD formulation.ResultsRegarding粉末表征，SD/PFD具有酒窝的表面，平均直径为1.793 μm。在下一代撞击器分析中，SD/PFD在不需要载体颗粒的情况下表现出高的体外吸入性能，并且计算出SD/PFD的细颗粒分数为62.4%。吹入SD/PFD（0.3 mg-PFD/大鼠）减弱了肺中抗原诱发的炎症事件，包括炎性细胞浸润和髓过氧化物酶活性。吸入SD/PFD后的有效剂量的PFD的全身暴露水平是600倍，低于后口服给药的PFD的光毒性dose.ConclusionSD/PFD将适合于吸入，利用RP系统与SD/PFD将提供一个更安全的药物相比，口服给药的PFD。
PurposePreviously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptablein vitroinhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method.MethodsSpray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations.ResultsRegarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated highin vitroinhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose.ConclusionSD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.