On-line monitoring of the freeze-drying process: A new image-based PAT.

In this work a Process Analytical Technology (PAT) for the on-line monitoring of a Vacuum Freeze-Drying (VFD) based on the information extracted from the infrared images of the process is presented and validated. An infrared camera, placed inside the drying chamber, provided information about the thermal evolution of the process over time; after images pretreatment and segmentation, temperature profiles were extracted and processed to obtain the variables of interest. Experiments were carried out according to factorial design on a set of different operating conditions, namely fluid temperature and chamber pressure, type of vials and solid percentage in the solution. Both sucrose and mannitol solutions, were studied. Together with the temperature in several positions along the product height, we were able to correctly estimate the ending time of the primary drying phase together with the sublimating interface position and the heat and mass transfer coefficients, Kv and Rp. Those two parameters have a dramatic importance since they can be used in a mathematical model of the process for on-line or off-line optimization of the process. Being based on a contactless technology, the PAT studied in this work does not present any issue regarding the sterility requirement of the process or the possible interference of the sensing element with the product dynamics.