Collapse temperature, freeze-drying

Collapse in freeze-drying occurs above a critical temperature, which allows viscous flow of freeze-concentrated amorphous solutes (Bellows and King 1973) as they are plasticized by unfrozen water (Roos 2004). The onset temperature of ice melting, T, can be used as a critical reference temperature for production of properly freeze-dried materials. 

It is important to select the components of the substrates with care and particularly to pay attention to the physical parameters they act upon, in particular the vitreous transition temperature (7g ) of the deep-frozen vaccine [20-25,30]. This temperature, also referred to as vitreous eutectic temperature, does indeed play a critical role in the deformation and collapsing of freeze-dried pellets [20,25], and possibly in the loss of infectivity titers. This temperature is dependent on the nature and concentration of the substrate molecules and may be determined in several ways [20,29,35,36]. In industrial practice, the most commonly utilized techniques are differential scanning calorimetry (DSC) as well as resistance and/or dielectric constant measurements. 

Fig. 1.44. Scanning electron-microscopic photographs of a vial containing freeze dried trehalose solution, (a), collapsed product from the bottom of the product (b), shrunk product after 6 months of storage at +20 °C with a RM too high and stored at a too high a temperature (Fig. 6 from [ 1.29]).

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... 

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