Department of Chemical Engineering, McMaster University, Hamilton, Ontario L8S 4L7, Canada.
McMaster Immunology Research Centre and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4L7, Canada.
Int J Pharm. 2019 May 30;563:71-78. doi: 10.1016/j.ijpharm.2019.03.026. Epub 2019 Mar 29.
Spray drying is emerging as a promising technique to produce thermally stable powder vaccines containing viral vectors. One of the most important factors in developing dry powder vaccines is the selection of the excipient carrier, however this process is time intensive, and uses large amounts of costly viral material. In this work, an acoustic levitator modified with a hot air delivery system was evaluated for its ability to mimic spray drying and acts as a screening method for excipient selection. The ability of three binary excipient blends to stabilize a human type 5 adenovirus was evaluated through an in vitro activity assay based on the expression of green fluorescent protein. Dried particle size and shape, glass transition temperature, moisture content, and crystallinity of powders produced by levitation and spray drying were compared. The particles created in the acoustic levitator under moderate heat can be considered representative of the powders that would be produced via spray drying. Viral vector titre losses differ between the methods, however, the trends with respect to excipient performance remain the same. Key material characteristics such as particle morphology and thermal properties are conserved when using the levitator. The acoustic levitator is a good starting point for dry powder vaccine development, and can be used to identify promising excipients while consuming minimal amounts of the viral vector.
喷雾干燥作为一种生产含有病毒载体的热稳定粉末疫苗的有前途的技术正在兴起。开发干粉疫苗最重要的因素之一是选择赋形剂载体，但这个过程既耗时又耗力，并且需要大量昂贵的病毒材料。在这项工作中，评估了经过改进的带有热空气输送系统的声悬浮装置模拟喷雾干燥的能力，并将其用作赋形剂选择的筛选方法。通过基于绿色荧光蛋白表达的体外活性测定评估了三种二元赋形剂混合物稳定人 5 型腺病毒的能力。比较了悬浮和喷雾干燥产生的粉末的干燥颗粒大小和形状、玻璃化转变温度、水分含量和结晶度。在适度加热下在声悬浮器中形成的颗粒可以被认为是通过喷雾干燥产生的粉末的代表。病毒载体效价损失在两种方法之间有所不同，但是，赋形剂性能的趋势保持不变。使用悬浮器时保留了关键的材料特性，例如颗粒形态和热性能。声悬浮器是干粉疫苗开发的良好起点，可用于在消耗最少病毒载体的情况下识别有前途的赋形剂。
