Cake Shrinkage During Freeze Drying: A Combined Experimental and Theoretical Study

The aim of this study is to investigate, by experimental studies and theoretical analysis, the phenomenon of cake shrinkage during the lyophilization process and to investigate the effect of shelf temperature during primary drying and secondary drying on the degree of cake shrinkage. Freeze-drying experiments were performed using 5% w/v sucrose where the drying protocols were altered in order to produce differing product temperature profiles. Resistance data during freeze drying were evaluated by the Manometric Temperature Measurement (MTM) method. Theoretical simulation of the freeze-drying process was performed using the Passage Freeze-Drying software. The difference between the glass transition temperature and the product temperature (Tg − T) obtained from the theoretical analysis was calculated and used for correlation with experimental shrinkage data. The Brunauer, Emmeth, Teller (BET) Specific Surface Area (SSA) Analysis was used as a method to quantify the degree of shrinkage. Samples were also analyzed for pore volume by mercury porosimetry. The SSA analysis on the freeze-dried samples showed an increase in SSA when samples were freeze dried at a lower shelf temperature during primary drying and at a slower ramp rate during secondary drying. The trend in surface area values was consistent with that obtained for pore size values. However, differences obtained among the various samples are small and cake diameter measurements showed that there was ~ 17% shrinkage even in the sample freeze dried at temperatures well below the Tg′ and Tg. Variations in process and product temperature only accounted for an additional 2%–3% shrinkage. Resistance data obtained at various primary drying shelf temperatures showed a good correlation with surface area. The Tg − T behavior of the freeze-dried samples showed that a slow ramp rate of 0.1°C/min during secondary drying maintains a product well below the Tg at all times and a higher ramp rate gives negative values of Tg − T. The obtained data suggest that conditions of secondary drying do impact shrinkage, and it is important to maintain a sample well below the collapse temperature during primary drying and below the Tg at all times during secondary drying; however, drying conditions are a second order effect. It seems that, in the case of a sample like sucrose, nearly 17% shrinkage will occur no matter what the product temperature history.