Science behind Lypholization (Al04-2016)

Mustafa Hamido

Freeze drying is a process where the material state is transferred from solid phase to gas phase without passing through a liquid phase. This technique is used in food processing, pharmaceutical preparations and all other applications where there is a need to remove water from the material without passing through a liquid phase of water.

Water content in any material influence on the quality of it. It decrease its stability and make it vulnerable to microorganisms’ growth. Furthermore, it speeds up its degradation and exposes it to number of chemical changes which influence on its quality and validity.

Science behind Lypholization

The science behind lypholization is simple. There is a point called a Triple point where there are an equilibrium between three phases of the material: gas, liquid and solid. For water. This point is defined as the point where liquid and solid status of any material coexist in stable equilibrium. For water this triple point exists at 0.01C, and at partial vapor pressure of 611.657 Pascals which equals 0.006 atm as shown the figure 1. 

Figure 1Water Sublimation Conditions

Suppose that any of the above conditions were changed either by decreasing it or increasing it, what will happen? Actually any slight decrease in the temperature or pressure will lead to something called sublimation. It is defined as the transition of the material directly from solid to gas without passing through liquid state. The above is the core of the lypholization process. Simply, Liquid state can be avoided by changing the temperature and pressure by decreasing them below the triple point of the material which there is a need to avoid its liquid state.

Lypholization process

This process is applied widely in pharmaceutics to avoid the existence of liquid water in the pharmaceutical preparation. Some times for some biologics, the existence of traces of water in the preparations maintain the protein structure. The talk is about small amount of water; however, the existence of high percentage of water decreases the stability of it and consequently its efficacy.

Lyphloization process includes the following steps concluded in the figure 2 below:

Figure 2 Lypholisation process

1. Freezing of the material at -50 C without any change in pressure (1000 atm)
2. Primary drying for 48 hours at -20 C and 0.1 mbar (9.8692e-5 atm)
3. Secondary drying for 4 hours at +20 C and 0.1 mbar (9.8692e-5 atm)

Those are the major steps for lypholization process. Some changes or differences can be noticed in the conditions of the steps above. That depend on the product, the validated lypholization method. Figure 3 below shows an example of lypholization process steps and cycle’s duration.

Figure 3Example of lypholization process steps and cycle's duration