Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada.
Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada.
Int J Pharm. 2021 May 15;601:120561. doi: 10.1016/j.ijpharm.2021.120561. Epub 2021 Mar 31.
This study investigates the ability of various shell-forming excipients to preserve the dispersibility of dry powder dosage forms, e.g., nasally administered vaccines, upon exposure to a high-humidity environment. Trehalose combinations using leucine, pullulan, or trileucine were selected as the candidate excipient systems, and the powder dispersibility of these systems was compared with that of pure trehalose particles. Scaled-up monodisperse spray drying was used to produce sufficient quantities of uniform-sized particles for powder dispersibility analysis. Particle size, crystallinity, and morphology of the powders before and after exposure to moisture were characterized by an aerodynamic particle sizer, Raman spectroscopy, and scanning electron microscopy, respectively. Three two-component particle systems composed of trehalose/trileucine (97/3 w/w), trehalose/pullulan (70/30 w/w), and trehalose/leucine (70/30 w/w) were first formulated and their dispersibility, characterized as the emitted dose from dry powder inhalers, was then compared with that of trehalose particles. The formulation containing 30% leucine maintained the highest emitted dose (90.3 ± 10%) at a 60 L/min flow rate after 60 min exposure to 90% RH and 25 °C, showing its superior protection against exposure to humidity compared with the other systems. Further investigations under more challenging conditions at a 15 L/min flow rate on the trehalose/leucine system with various compositions (70/30, 80/20, 90/10 w/w) showed that a higher leucine concentration generally provided better protection against moisture and maintained higher powder dispersibility, probably due to higher surface coverage of crystalline leucine and a thicker leucine shell around the particle. The study concludes that leucine may be considered an appropriate shell-forming excipient in the development of dry powder formulations in order to protect the dosage forms against humidity during administration.
本研究考察了各种包衣辅料在暴露于高湿度环境时保持干粉剂型（例如鼻内给予的疫苗）分散性的能力。选择海藻糖与亮氨酸、普鲁兰或三亮氨酸的组合作为候选辅料系统，并将这些系统的粉末分散性与纯海藻糖颗粒的粉末分散性进行了比较。采用规模化单分散喷雾干燥技术生产足够数量的均匀粒径颗粒，用于粉末分散性分析。使用空气动力学粒度分析仪、拉曼光谱和扫描电子显微镜分别对暴露于水分前后的粉末的粒径、结晶度和形态进行了表征。首先配制了由海藻糖/三亮氨酸（97/3 w/w）、海藻糖/普鲁兰（70/30 w/w）和海藻糖/亮氨酸（70/30 w/w）组成的三个二组分颗粒系统，并比较了它们的分散性，以干粉吸入器的发射剂量来表示。在 60%相对湿度和 25°C 下暴露 60 分钟后，含 30%亮氨酸的制剂在 60 L/min 的流速下保持最高的发射剂量（90.3±10%），表明其在暴露于湿度方面优于其他系统。在 15 L/min 的流速下，对各种组成（70/30、80/20、90/10 w/w）的海藻糖/亮氨酸系统进行更具挑战性条件下的进一步研究表明，亮氨酸浓度越高通常能提供更好的防潮保护，并保持更高的粉末分散性，这可能是由于结晶亮氨酸的表面覆盖率更高，颗粒周围的亮氨酸壳更厚。研究得出结论，亮氨酸可用作干粉制剂开发中的合适包衣辅料，以保护制剂在给药过程中免受湿度影响。
