Collapse temperature, in freeze-drying

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... 

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. 

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. 

Fig. 13 Chemical degradation in freeze dried hGH formulated with trehalose as a function of water content at 40 C and 50°C. The pseudo first-order rate constant for degradation (%/month) is given for the combination of asparagine deamidation and methionine oxidation. The formulation is hGH trehalose in a 1 6 weight ratio with sodium phosphate buffer (pH 7.4) at 15% of the hGH content. The highest moisture content samples were collapsed after storage at both 40°C (moderate collapse) and 50°C (severe collapse). The water content that reduces the glass transition temperature of the formulation to the storage temperature is denoted Wg. O = 40°C storage = 50°C storage. (From Ref. l)...

One other point of interest of thermal analysis in freeze drying is the use in examining phase concentration. Frequently, inert sugars or polyhydric alcohols such as mannitol or sucrose are included in solutions to be freeze dried. Roos [157] reviewed the frozen state transitions in relation to freeze-drying. It is these conditions that should be used to derive a proper freeze-drying condition. Freeze-dried products should be porous and easy to hydrate. However if collapse occurs during dehydration a product may exhibit poor dehydration properties. Collapse occurs if the temperature of ice is higher than the collapse temperature, of a material. 

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. 

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