Department of Mechanical Engineering, University of Alberta, Edmonton, Canada.
Department of Mechanical Engineering, University of Alberta, Edmonton, Canada.
Int J Pharm. 2019 May 30;563:156-168. doi: 10.1016/j.ijpharm.2019.04.004. Epub 2019 Apr 2.
Spray drying biologics and small-molecule drugs can increase their thermal stability relative to liquid dosage forms and allow for widespread distribution to developing countries without cold chain infrastructure. In this study, pullulan trehalose powder is spray dried for inhalation. The powder is characterized in terms of manufacturability, physical stability, device compatibility, and aerosol performance. The manufacturability is demonstrated by reasonable spray drying yield and powder flowability. The powder has relatively low cohesiveness and high compressibility without semi-elastic deformation. Short-term physical stability for ambient temperature dry storage and 40 °C storage in commercial pressurized metered-dose inhaler propellants HFA 134a and HFA 227 is shown. A theoretical model predicts a high glass transition temperature near the surface of the microparticles where biologics are expected to reside. Emission from a commercial dry powder inhaler demonstrates high dispersibility, optimal size for inhalation, and adequate total lung dose, exceeding many commercial inhalation devices. The powder can be filled, stored, and actuated from a pressurized metered-dose inhaler without changes in particle morphology or solid phase. The pullulan trehalose platform thus appears promising for respiratory delivery.
喷雾干燥生物制剂和小分子药物可以提高它们相对于液体剂型的热稳定性，并允许在没有冷链基础设施的情况下广泛分发给发展中国家。在这项研究中，使用普鲁兰海藻糖粉末进行吸入喷雾干燥。从可制造性、物理稳定性、装置兼容性和气溶胶性能方面对粉末进行了表征。通过合理的喷雾干燥收率和粉末流动性证明了可制造性。该粉末具有相对较低的内聚性和高压缩性，没有半弹性变形。在环境温度干燥储存和在商业加压计量吸入器推进剂 HFA 134a 和 HFA 227 中 40°C 储存的短期物理稳定性得到了证明。理论模型预测，在生物制剂预期存在的微粒表面附近存在高玻璃化转变温度。来自商业干粉吸入器的发射显示出高分散性、适合吸入的最佳粒径和足够的全肺剂量，超过许多商业吸入装置。该粉末可以从加压计量吸入器中填充、储存和启动，而不会改变颗粒形态或固体相。因此，普鲁兰海藻糖平台似乎很有希望用于呼吸道给药。
