Secondary drying desorption

Secondary Drying Desorption of Water from the Freeze Concentrate... 

Secondary drying (desorption) to remove structured, more tightly bound... 

Even after all ice has been removed by sublimation, the product phase, or freeze concentrate, contains a large amount of dissolved water that must be removed to produce a stable product. This water is removed by desorption during secondary drying. Secondary drying is usually carried out at elevated product temperature to achieve efficient water removal. 

For a product a reproducible desorption isotherm exists, and the product does not change at the end temperature during secondary drying. 

After the ice has been sublimed, the adsorbed water is desorbed from the solid. This process is governed by laws different from those of the main drying. This step is called secondary or desorption drying. During the secondary drying (SD) the ener-... 

The secondary drying is governed by two factors the temperature of the product and the binding energy of the water to the solid. The desorption rate DR is the tool to monitor its progress (see Section 1.2.3) ... 

Secondary drying is generally carried out under higher vacuum when the product has reached an above-zero temperature (or its electric impedance has reached the upper limit). Indeed, it has been shown by different authors that isothermal desorption was faster and allowed lower final residual moistures when the pressure lay in the level of 10 mbar, but that higher vacuums (10 mbar) did not drastically improve the operation. 

The secondary drying will be terminated after the product has reached its final temperature and the desorption rate the desired value. If also RM values determined with the Karl Fischer method are required, three coded vials at a time will be closed with a manipulator parallel to the DR measurements and could be removed (Figure 26). 

Figure 26 Freeze-drying of cytostatica. The high desorption rate value (x) and the scattering of the residual moisture determined with the Karl Fischer method ( ) confirms that the transition phase from main drying to secondary drying was not finished after 22.5 h. The secondary drying could be terminated after 28 h. Product temperature (A).

Secondary drying Shelf temperature profile, maximum operation pressure, maximum condenser temperature and desorption rates to determine the end of. secondary drying. 

Before concentrating on process parameters (Section III), we will briefly outline the behavior of the product during the three separate but interdependent stages of freeze-drying freezing, sublimation (primary drying), and desorption (secondary drying). 

Despite the practical importance of determining the point where primary drying terminates, there is no easy or universally recognized method to do this. Part of the difficulty arises from the fact that the boundary between primary and secondary drying is not clear-cut. A reason for this is that the upper part of the cake is subject to a limited water desorption whereas the bottom of the cake is still undergoing sublimation. Another reason is that all of the samples do not necessarily dry at the same rate [3] because freezing-drying is inherently a statistical process in many respects. 

The time needed to complete desorption is highly dependent on product formulation and drying temperature. Crystalline mannitol usually requires only a short secondary drying, because the amount of bound water is minimal. On the other hand, glass-like systems formulated with sucrose or lactose necessitate a prolonged secondary drying. 

For effective desorption, the chamber pressure should be sufficiently low at the terminal stage of secondary drying. A maximum acceptable pressure should be specified. 

In contrast with the situation of primary drying, a low-temperature condenser is a great asset during secondary drying for formulations that must be dried to very low residual moisture. As the vapor pressure over ice is 0.5 microbars at -80°C versus 11 microbars at -60°C, the desorption of water can be achieved in a more complete way with a condenser cooled at -80°C. 

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