Principles of Lyophilization Equipment

Wet samples can be frozen by placing them in a vacuum. The more energetic molecules escape, and the temperature of the sample falls by evaporative cooling. Eventually it freezes. About 15% of the water in the wet material is lost.

The simplest form of lyophilizer would consist of a vacuum chamber into which wet sample material could be placed, together with a means of removing water vapor so as to freeze the sample by evaporative cooling and freezing and then maintain the water-vapor pressure below the triple-point pressure. The temperature of the sample would then continue to fall below the freezing point and sublimation would slow down until the rate of heat gain in the sample by conduction, convection, and radiation was equal to the rate of heat loss as the more energetic molecules sublimed away were removed.

This simple approach creates numerous difficulties. When a material is frozen by evaporative cooling it froths as it boils. This frothing can be suppressed by low-speed centrifugation. Centrifugation also helps to dry faster by reducing material thickness and exposing a greater surface area.

An alternative is to freeze the material before it is placed under vacuum. This is commonly done with small laboratory lyophilizers where material is frozen inside a flask. The flask is then attached to a manifold connected to the ice condenser. To speed the process the material can be shell-frozen by rotating the flask in a low-temperature bath, giving a large surface area and small thickness of material.

For larger-scale equipment it is usual to place the material on product-support shelves inside the drying chamber, which can be cooled so that the material is frozen at atmospheric pressure before the vacuum is created. Without a controlled heat in[put to the sample its temperature would fall until drying was virtually at a standstill. For this reason it is usual to arrange a heat supply to the product-support shelves so that, after their initial use for freezing the product, they can be used to provide heat to replace the energy lost with the subliming water vapor and maintain the product at a constant low temperature.

One milliliter of ice produces more than 1,000,000 ml. of water vapor at typical lyophilization cycle pressures. The more energy-efficient vacuum pumps cannot handle large quantities of water vapor. For this reason it is usual to fit a refrigerated trap (called the ice condenser) between the lyophilization chamber and the vacuum pump. Modern lyophilizers incorporate refinements.

The most important are listed below:

Click here to see an industrial lyophilizer.

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