Non-invasive temperature monitoring: controlled nucleation as a case study

Freeze-drying is employed in pharmaceutical industry to preserve thermo-sensitive products. It is a cost intensive process and, for its optimisation, it is important to maximise the ice sublimation rate during primary drying, thus reducing cycle duration. At this purpose, it is fundamental to monitor the product temperature and keep it at a value lower than that at which melting or collapse occurs. The temperature monitoring is also important during the freezing stage as it influences the two subsequent drying stages. In particular, the temperature of ice nucleation determines the size of ice crystals and the morphology of the frozen cake, thus impacting on the final properties of the product. Moreover, as the nucleation of ice is a stochastic event and it is not certain that all the vials in the batch nucleate at the same temperature (allowing a non-homogeneous product structure and subsequent drying behaviour), several techniques have been proposed for inducing the nucleation at a certain temperature and time and make the process more cost efficient

Process Analytical Technology for monitoring pharmaceuticals freeze drying - A Comprehensive Review

The goal of this paper is to review the available process analytical technology tools for monitoring the batch freeze-drying process for pharmaceuticals. These systems aim evaluating in-line product temperature, sublimation flow rate, and values of some model parameters in such a way that it can be used for in-line or off-line process optimization. A detailed survey of the systems proposed in the literature is presented, grouping them on the basis of monitored variable, namely, product temperature, heat flux to the product, sublimation flux, and, finally, other variables. The advantages and drawbacks of the techniques are critically assessed, taking into account the possibility of using them not only at lab-scale but also at production scale, beside, obviously, the possibility of getting reliable measurements of the desired variables

Real-time temperature monitoring in pharmaceutical freeze-drying

In this study, a thermocouple array realized by using thin film strips is employed for real-time temperature measurements during pharmaceutical freeze-drying. The thin film thermocouple array is directly deposited on the vial walls and can be employed to monitor the temperature evolution during the freezing stage. Freezing is a critical stage of the entire cycle, since the nucleation temperature influences the morphology of the dried material and, consequently, the subsequent drying phase. Since conventional thermocouples are too invasive, due to the high thermal conductivity of the metallic wires, which alter the product nucleation, innovative measuring approaches have to be developed and validated to optimize the drying cycles. Moreover, conventional thermocouples allow only one-point measurement to be obtained, while the possibility of realizing thermocouple arrays offered by the thin film technology, can give more reliable results

Real-time temperature monitoring in pharmaceutical freeze-drying

In this study, a thermocouple array realized by using thin film strips is employed for real-time temperature measurements during pharmaceutical freeze-drying. The thin film thermocouple array is directly deposited on the vial walls and can be employed to monitor the temperature evolution during the freezing stage. Freezing is a critical stage of the entire cycle, since the nucleation temperature influences the morphology of the dried material and, consequently, the subsequent drying phase. Since conventional thermocouples are too invasive, due to the high thermal conductivity of the metallic wires, which alter the product nucleation, innovative measuring approaches have to be developed and validated to optimize the drying cycles. Moreover, conventional thermocouples allow only one-point measurement to be obtained, while the possibility of realizing thermocouple arrays offered by the thin film technology, can give more reliable results