Comparison of vial heat transfer coefficients during the primary and secondary drying stages of freeze-drying

Abstract

This study uses a heat flux sensor and temperature probes to directly measure vial heat transfer coefficients (Kv) during primary and secondary drying stages of lyophilization. It is observed that Kv is 40–80% smaller during secondary drying than primary drying, and this value exhibits a weaker dependence on chamber pressure than in primary drying. These observations arise because water vapor in the chamber significantly decreases between primary and secondary drying, which alters the gas conductivity between the shelf and vial. This study tabulates Kv values for secondary drying for different vials and different chamber pressures, and demarcates the contributions from gas conduction. Lastly, the study performs an energy budget analysis on two different vials (10R glass vial and 10 mL plastic vial) to determine the major factors that contribute to vial energy consumption. During primary drying, the majority of energy supplied goes towards sublimation, while for secondary drying, the majority of energy goes towards heating the vial wall rather than desorbing bound water. We discuss the consequences of this behavior for heat transfer modeling. During secondary drying, the heat of desorption can be neglected in thermal modeling for some materials (e.g., glass) but not others (e.g., plastic vials).