Pressure in Primary drying phase of Lyophilization

Hi Folks,

Now Let's have look on Primary drying phase aka sublimation phase that will follow when the frozen material, placed under vacuum, is progressively heated to deliver enough energy for the ice to sublime.

During this very critical period a correct balance has to be adjusted between heat input (heat transfer) and water sublimation (mass transfer) so that drying can proceed without inducing adverse reactions in the frozen material such as back melting, puffing, or collapse.

A continuous and precise adjustment of the operating pressure is then compulsory to link

the heat input to the “evaporative possibilities” of the frozen material.

Primary drying is carried out at low pressure to improve the rate of ice sublimation. The chamber pressure impacts both heat and mass transfer and is an important parameter for freeze-drying process design. Chamber pressure should be well below the ice vapor pressure at the target product temperature to allow a high sublimation rate.

The sublimation rate is proportional to pressure difference between the vapor pressure of ice and the partial pressure of water in the chamber (Pi), this difference being the driving force for ice sublimation. Pi is essentially the same as chamber pressure during primary drying. At given product

temperature (i.e., given ice vapor pressure), the smallest chamber pressure gives the highest ice sublimation rate.

So, as per the above concept let us set the vacuum set point for primary drying step. (temperature selection done as per previous posts).

A recommended approach is to first set the system pressure using the vapor pressure of ice table. 

Using the vapor pressure of ice table is a scientific way to determine an appropriate pressure for freeze drying. A general guideline is to choose a system pressure that is 20% to 30% of the vapor pressure of ice at the target product temperature. When the vacuum level set point is deeper than the vapor pressure of ice at the current product temperature, sublimation can take place. 

Herewith attached the vapor pressure of Ice table.

During the Initial days of the Lyophilization utilization, it is believed that higher the vacuum the better the sublimation process could be. 

However, very low chamber pressure may cause problems, such as contamination of product with volatile stopper components or pump oil, and also produce larger heterogeneity in heat transfer, thereby giving larger product temperature heterogeneity between vials. In most applications of practical interest, the chamber pressure varies from 50 to 200 mTorr. It is difficult to maintain consistently chamber pressure much below 50 mTorrr, and there is little reason to use pressures much higher than 200 mTorr. It has been reported that moderate chamber pressure (100–150 mTorr) gives optimal homogeneity of heat transfer in a set of vials.Therefore, the optimum chamber pressure is a compromise between high sublimation rate and homogenous heat transfer.

Thats how vacuum is set for primary drying folks.

Yours,
Teja Ponduri