Freeze-Drying Monitoring Using a New Process Analytical Technology: Toward a “Zero Defect” Process

Abstract

This article presents a new process analytical technology to monitor a vial freeze-drying process taking into account the batch nonuniformity. It is based on a soft sensor, using a mathematical model of the process, and on the temperature measurement obtained using a new wireless device. It allows estimating the residual ice content in the monitored vials until the end of the primary drying stage and the values of the heat (and mass transfer) coefficients. Experiments carried out with aqueous solutions containing various excipients (sucrose, mannitol, polyvinylpyrrolidone) or with a pharmaceutical formulations show the effectiveness of the proposed system.

Keywords:

• Freeze drying
• Monitoring
• PAT
• Soft sensor
• Wireless temperature measurement