Freeze drying, also known as lyophilization, is the process of rapidly freezing a liquid product and then dehydrating the product under vacuum, resulting in a dry product. Freeze drying uses sublimation, which is the phase change process from solid to gas, skipping the liquid phase.
Freeze drying extends the life of pharmaceutical products. This can be important during long periods of product storage and transportation. The original product can be reconstructed by adding water when necessary.
Freeze drying is a largely used process in the pharmaceutical and biotech industries:
- Oncology APIs
The Freeze Drying Principle
A – Going from solid (ice) to gas (water vapor) avoiding the triple point (vacuum).
B – Trapping the water vapor onto a cold surface (condenser).
There are 3 stages in lyophilization:
- Primary Drying (Sublimation)
- Secondary Drying (Desorption)
Slow freezing of the aqueous product happens on shelves in a vacuum chamber, around -45°C creating large ice crystals. The crystal size is dependent on several factors, however larger ice crystals allow faster sublimation.
Primary drying is when sublimation takes place. This process removes around 98% of water in the product. Heat energy drives the sublimation process, the phase change from solid to gas. Three methods of heat transfer are involved:
Conduction: contact between the shelves and vials/trays
Convection: Nitrogen gas or air is injected into the chamber to support heat transfer. The process is controlled with a micrometric needle valve.
Radiation: protect against radiation to promote even drying.
When there is no more free water, sublimation stops.
In this stage, the last 2-3% of water remaining is removed (desorbed). This stage requires a lot of energy: more heat (45°C) and more vacuum (50µb or less). The air inside the chamber is reduced to its minimum, so there is no convection in this phase, only conduction.
Once the freeze-drying process is over, the next steps include:
- Pressure test – to measure residual moisture content
- Stoppering of vials
- Unloading – can be manual or automatic
- De-icing of the condenser
ACIC Machinery provides a wide range of solutions for your freeze-drying needs, from lab scale and small production, to large industrial scale. We provide freeze-dryers with loading/unloading systems, integrated isolators, and CIP/SIP. Go to our Freeze Dryers Page to learn more.
1. Our partner Criofarma
2. Barley, J. Basic Principles of Freeze Drying. SP Scientific. Retrieved from https://www.spscientific.com/freeze-drying-lyophilization-basics/.