Calorimetric monitoring of lyophilization

This paper describes an apparatus and method for monitoring the lyophilization of a formulation by using calorimetric measurements. From calorimetric measurements, the energy transferred during each phase of the process can be determined. A brief review of the existing monitoring methods shows that they possess no direct relationship to the thermal energy that represents the real driving force for the lyophilization process. A general description of the apparatus is presented with special emphasis made on the sensor construction and calibration. The means for determining the heat transfer rate (Qm) and total energy (Hm) for each step of the process are described. The use of calorimetric measurements are demonstrated by showing actual thermographs of freezing, primary drying and secondary drying processes for several formulations. Some key advantages of calorimetric monitoring of the lyophilization process are demonstrated by accurately determining the completion of the primary drying and detection of exothermic reactions during the secondary drying.