Freeze collapse temperature

Fig. 1.53. Freezing and thawing plot of coffee extract with 25 % solids. UFW (g H20/g solids) as a function of temperature (Fig. 2 from [ 1.37])-I, Subcooling 2, collapse temperature.

The frequency at the minimum of this curve is called TOF by the authors. TOF varies with the temperature as shown in Fig. 1.55.6. The extrapolated intersection of the two linear portions identifies the collapse temperature. The predicted Tc by TOF for 10 % sucrose, 10 % trehalose, 10 % sorbitol and 11 % Azactam solution deviates from observations by a freeze-drying microscope (Table 1, from [1.126]) to slightly lower temperatures, the differences are -3 °C, -1.4 °C, 2.2 °C and 0.7 °C. 

Pikal, M.J., Shah, S. The collapse temperature in freeze-drying dependence on measurement methodology and rate of water removal from the glassy phase. Int. J. Pharm. 62,165-186,1990 Thijssen, H.A.C., Rulkens, W.H. Effect of freezing rate on rate of sublimation and flavour retention in freeze-drying, pp. 99-114. International Institute of Refrigeration (HR) (Comm. X, Lausanne), 1969... 

Tight containers, protected from light, and avoid prolonged exposure to temperatures exceeding 30 °C Collapsible tubes or tight containers store at 25 °C excursions permitted between 15 and 30 protect from freezing Collapsible tubes at controlled room temperature... 

Particularly for freeze-dried products, formulation and process are interrelated. Properties of the formulation, in particular the collapse temperature, will have a significant impact on the ease of processing. An efficient process is one that runs a high product temperature. However, the temperature cannot be too high or product quality will be compromised. As the glass transition temperature depends on chemical composition of the amorphous phase, Tg and collapse temperature are strongly formulation dependent. Collapse temperatures for common excipient systems vary from less than —50°C to around —10°C (Table 2). 

Pikal, M. J. Shah, S. The collapse temperature in freeze drying dependence on measurement methodology and rate of water removal from the glassy phase. Int. J. Pharm. 1990, 62, 165-186. 

In order to freeze the product, the shelf temperature is reduced to a level well below the collapse temperature. Depending on the dimensions of the container and on the fill volume of the product, the product temperature is maintained at shelf level for a specified period of time to ensure the formation of a completely frozen matrix. 

A comparable phenomenon is that a solid material obtained by freeze drying can change into a highly viscous liquid upon increasing water content or temperature this is generally called collapse, since the desirable porous structure of the freeze-dried product is lost. The collapse temperature tends to be a few kelvins above Tg. 

Barresi, A., Ghio, S., Fissore, D., Pisano, R. (2009). Freeze drying of pharmaceutical excipients close to collapse temperature influence of the process conditions on process time and product quality technology. Drying Technology, 27, 805-816. 

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