Several Key Temperatures During Freeze-Drying Process

Several Key Temperatures During Freeze-Drying Process

Freeze-drying technology boasts numerous advantages. While its principles are simple, practical control during process optimization is challenging. Before exploring and optimizing the freeze-drying curve, it is essential to determine the eutectic point, glass transition temperature, eutectic melting point, and collapse temperature of the product.

Eutectic Point (Crystalline)

During the pre-freezing process of the product in crystalline systems, as the temperature decreases, ice nuclei form below the freezing point (the temperature at which substances begin to freeze). These nuclei gradually grow, increasing the concentration of solutes in the remaining solution. Upon reaching supersaturation, crystallization occurs. The temperature continues to decrease until the remaining solution solidifies completely into a mixture of ice and solute crystals. This temperature is known as the eutectic point. For some substances, the eutectic point isn't a specific temperature but rather a range.

If the product is not completely solidified during pre-freezing, some liquid material remains. During the sublimation drying stage, this can lead to "bubbling," where the liquid material boils under low pressure. This phenomenon can cause uneven internal structure after freeze-drying, resulting in clumping of materials and poor reconstitution. Thus, the eutectic point temperature is a critical temperature during pre-freezing. Only by freezing below the eutectic point can all moisture in the product condense and solidify.

Glass Transition Temperature (Amorphous Materials)

In amorphous systems, during the pre-freezing of the product, when the temperature drops sufficiently, the ice crystals cease to grow further. The remaining solution reaches maximum concentration, forming a highly viscous glassy state with solutes and residual water. The temperature at this point is the glass transition temperature. Apart from material composition, this temperature depends closely on the structure of the material, pre-freezing temperature, and rate.

Eutectic Melting Point (Crystalline)

During the drying process, as the temperature gradually increases, the fully solidified solutes and solvents begin to melt. This temperature is the eutectic melting point, the point at which melting begins. Therefore, this temperature is the maximum allowable temperature for crystalline substances during the sublimation stage. It is crucial to ensure that the product remains below this temperature; otherwise, evaporation or boiling may occur.

Collapse Temperature (Amorphous Materials)

During drying, when the temperature of the drying layer rises to a certain value, ice crystals within the product disappear. The space formerly occupied by ice crystals becomes voids, creating a porous honeycomb-like sponge structure. When the temperature of the solid matrix of this honeycomb structure is high, its rigidity decreases. Upon reaching a critical value, the rigidity of the solid matrix is insufficient to maintain the honeycomb structure, leading to collapse of the walls of the voids. This blocks the pathways for vapor diffusion, preventing further sublimation and ultimately resulting in excessive moisture content in the final product. This critical temperature is known as the collapse temperature.