A method for on-line determination of residual water content and sublimation end-point during freeze-drying

Freeze-drying is a discontinuous process mainly used in the food and pharmaceutical industry to preserve the initial properties of raw products after dehydration. To date, the freeze-drying process has been monitored according to time-dependent empirical rules. Several authors have attempted to develop measuring systems for the on-line determination of the dehydration rate (freeze-drying kinetics) and the sublimation end-point. Of the various measurement systems tested, the measurement of the partial pressure of water vapour by a moisture sensor appears to be the best. Nevertheless, no theoretical background has been advanced to explain the relationship existing between the moisture measurement and the freeze-drying kinetics. This can be achieved using the standard laws of mass transfer corresponding to either a diffusion-driven process or diffusion through a stagnant medium. Moreover, estimation of the sublimation end-point is rigorously possible by referring to these mass-transfer laws. A time-dependent function requiring only the measurement of the operating conditions, and particularly the partial pressure of water vapour inside the apparatus, has been established.