(81c) Understanding of Heat Transfer in Freeze-Dryer during Primary and Secondary Drying Stages: Considerations of Vial’s Thermal Properties

Freeze drying is a widely used process that improves the stability of pharmaceutical products. This process is time and energy intensive, and thus there is a strong need to understand and improve its heat transfer. Freeze drying consists of two stages: (a) primary drying (sublimation of ice), and (b) secondary drying (desorption of bound water). For primary drying, the heat transfer resistance between a shelf and a vial is inferred through changes in mass, and it is often assumed that this resistance remains the same during secondary drying. However, our recent study demonstrated that the heat transfer coefficient during secondary drying is much different than the measured value during primary drying due to changes in moisture content in the chamber. Additionally, unlike primary drying, the thermal properties of the vial play a much larger role in the temperature profile during secondary drying. To deeply investigate these observations, we performed careful measurements of the heat transfer in freeze dryer during primary and secondary drying using a lab-scale lyophilizer.

The purpose of this study is to determine the impact of different vials and their thermal properties on the vial heat transfer throughout the primary and secondary drying stages. We lyophilized different sugars (e.g., sucrose and mannitol) under a wide range of operating conditions in order to determine their influence on the energy transfer during secondary drying. Gravimetric and heat flow analysis methods were used to calculate the vial heat transfer coefficient K_v for multiple vial systems in a lab-scale freeze-dryer. Secondly, an energy budget analysis was used to determine the influence of the thermal mass of vials on the heat transfer characteristics of the secondary drying process.

Our findings revealed distinct heat transfer characteristics during the primary and secondary drying processes, as well as changes in the heat transfer coefficient for various vial compositions. Correlation parameters between heat transfer coefficient and chamber pressure are estimated using the data collected from various vials. Heat transfer characteristics explored in this study have great potential for minimizing the uncertainties in secondary drying modeling. It is expected that our results will aid in understanding and optimizing secondary drying for the lyophilized product.