In-line monitoring of the primary drying phase of the freeze-drying process in vial by means of a Kalman filter based observer

The authors acknowledge the Chemical Engineering Research & Design journal for their copyright policies & self-archiving. More open access publications of Hassan Hammouri are available on: http://hal.archives-ouvertes.fr/HAMMOURI-HASSAN See also http://www.researcherid.com/rid/D-1685-2009International audienceThis paper is focused on the monitoring of the primary drying phase of the lyophilisation process of pharmaceuticals in vial. Monitoring is required to ensure that the maximum temperature of the product is maintained at a safe value in order to avoid denaturation, and the position of the moving front of sublimation has to be monitored since its evolution gives the state of progression of the primary drying. Furthermore, the information coming from the monitoring system, which includes the estimation of the transport coefficients, can be used in a control loop designed to minimise the drying time beside ensuring product quality. To this purpose, a soft-sensor (observer) has been developed, based on the extended Kalman filter algorithm: it requires a model of the process (a simplified model is used in order to reduce the computational load) and some physical measurements (in this case the temperature of the product at the bottom of the vial, that can be measured by a thermocouple). The main issues arising in the design of this observer have been discussed. A detailed mono-dimensional model experimentally validated has been used at first to compare the results provided by the observer by means of numerical simulations, and then the results obtained in a pilot freeze-dryer are shown