The influence of thermal radiation during microwave-assisted freeze-drying of pharmaceutical unit doses.

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.