Development of a High Gain Observer for In-Line Monitoring of Sublimation in Vial Freeze Drying

作者：Velardi Salvatore A; Hammouri Hassan; Barresi Antonello A^*

来源：Drying Technology, 2010, 28(2): 256-268.

DOI：10.1080/07373930903530204

• Extended Kalman filter
• Freeze drying
• High gain observer
• Lyophilization
• Modeling
• Monitoring
• Primary drying

In-line monitoring of the primary drying of the lyophilization process of a pharmaceutical product in vials is addressed in this article. A soft sensor (observer) based on the high gain concept is designed to this purpose. The proposed observer combines the physical measure of the frozen product temperature at the bottom of the vial with a simplified mathematical model of the process. This approach allows the continuous estimation of the entire temperature profile of the product and the monitoring of the state of progression of the primary drying phase. The main issues arising in the design of this observer are discussed. A detailed and experimentally validated mono-dimensional model is used as a source of measured data, in order to compare and validate by means of numerical simulations the results provided by the soft sensor. Finally, the performance of the high gain observer is compared with that of a Kalman filter-based observer previously proposed for the same process, evidencing the advantages of the high gain approach.

• 出版日期2010