Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
GSK, Rue de l'Institut 89, Rixensart 1330, Belgium.
Int J Pharm. 2024 Oct 25;664:124640. doi: 10.1016/j.ijpharm.2024.124640. Epub 2024 Aug 25.
New drying technologies for biologicals have recently been developed to accelerate the time-consuming batch freeze-drying (BFD) process. Among others, microwave-assisted freeze-drying (MFD) has been suggested as a faster and more effective drying technology. In this study, MFD cycles with the microwave radiation switched on and off were performed to assess the contribution of the microwave radiation to drying acceleration. It was found that thermal radiation emitted by the drying chamber walls was predominantly accelerating the drying of monodose placebos rather than microwave radiation. The combination of ultra-low chamber pressure, high thermal heat transfer and a short primary-to-secondary phase transition reduces drying times by more than 80 % compared to conventional BFD. In a second step, a design of experiment approach was used to assess the effect of thermal radiation versus microwave radiation and their combination, together with dosage properties such as fill volume and excipient concentration upon drying rate. The outcome showed the importance of high fill volume and high excipient concentration for an effective microwave contribution to the drying rate. Nevertheless, the drying acceleration for small pharmaceutical dosages with restricted solutes was mainly driven by thermal radiation rather than 2.45 GHz microwave radiation. The inability of ice to convert microwave energy into heat hampers the potential use of microwave freeze-drying for single-dose vaccines.
最近开发了新的生物制品干燥技术，以加速耗时的批量冷冻干燥（BFD）过程。其中，微波辅助冷冻干燥（MFD）已被提议作为一种更快、更有效的干燥技术。在这项研究中，进行了开启和关闭微波辐射的 MFD 循环，以评估微波辐射对干燥加速的贡献。结果发现，干燥室壁发出的热辐射主要加速了单剂量安慰剂的干燥，而不是微波辐射。与传统的 BFD 相比，超低腔压、高热传递和较短的主次相变相结合，将干燥时间缩短了 80%以上。在第二步中，使用实验设计方法评估了热辐射与微波辐射及其组合以及剂量特性（如填充体积和赋形剂浓度）对干燥速率的影响。结果表明，高填充体积和高赋形剂浓度对于微波对干燥速率的有效贡献非常重要。然而，对于具有受限溶质的小药物剂量，干燥加速主要是由热辐射驱动，而不是 2.45GHz 微波辐射。冰无法将微波能量转化为热量，这阻碍了微波冷冻干燥在单剂量疫苗中的潜在应用。
