Manufacturing and Bioprocessing
2019 PharmSci 360
Heat and mass transfer are essential parameters for the design and optimization of freeze drying processes. Heat flux sensors (HFS) are a promising PAT tool to obtain key parameters to describe these parameters. We assessed the applicability and advantages of HFS in comparison to the labor-intensive, classic and well-established gravimetric methodology to determine the heat transfer coefficient (Kv).
We could show how this extremely fast HFS analysis is in good agreement with the gravimetric result for Kv. In addition, the use of HFS enables to generate a primary drying (PD) design space in one single experiment. This allows to support a Quality-by-Design development and to select shelf temperature and chamber pressure ensuring the critical quality attributes. PD simulations based on the parameters derived by HFS are a very good starting point for lyophilization process development, scale-up and transfer, considering the max sublimation flux allowable for the target freeze dryer.