Obtaining heat transfer coefficients (K) distribution directly from mass flow measurements during the sublimation step of freeze-drying.

The knowledge of heat transfer coefficients (K) and their distribution is a crucial element in the successful transfer of a freeze-drying process to a new piece of equipment. Nevertheless, the implementation of the classical ice sublimation method is resource consuming, particularly in the industrial context, which represents a significant barrier to its application. This paper demonstrates that the K distribution can be calculated from the measurement of mass flow during a freeze-drying operation by reversing the results of process simulation calculations. This methodology works independently of the experimental method used to measure the mass flux: tunable diode laser absorption, inlet/outlet temperature difference of the shelves, or chamber/ condenser pressure difference. The advantage of this new method is that it requires no specific experimental effort and can be carried out on routine production runs (especially with the temperature or pressure difference methods), provided the freeze drier possesses at least shelf inlet/outlet temperature measurement and/or chamber and condenser capacitance pressure measurement. Furthermore, the measurement encompasses all vials, which is not achievable using the conventional method for commercial units that contain tens of thousands of vials. Once fed back into the primary drying mechanistic model, the K distribution is used to estimate the temperature distribution in the product. In this article, we provide practical examples at all scales, from laboratory to industrial production.