The 4 Stages of Lyophilization

Lack of moisture keeps food fresh; the same goes for drug products.

Freeze-drying, also known as lyophilization, is a method used to remove water from a drug product in order to preserve its long-term stability. The process begins by freezing the product, followed by a reduction in pressure and the application of heat, which allows the frozen water within the product to sublimate. 

This process involves several key components: a product chamber, a condenser, and systems designed to control vacuum, refrigeration, and heating.

1. Freezing

The solvent, water, is cooled until it freezes inside the product chamber. Since the product in the solvent has a lower freezing point, the temperature is further decreased until the solution is fully frozen. Meanwhile, the condenser is cooled below the shelf temperature to maintain the process.

2. Primary Drying

The isolation valve opens, and a vacuum pump removes air from both chambers. As pressure drops, the temperature rises, causing ice crystals to sublimate into vapour. The vapour rises, leaving the dried product behind, and condenses on the cold coils of the condenser. That is because the vapour naturally flows from the highest pressure region to the lowest pressure region. By the end, 90% of the water is removed.

3. Secondary Drying

To remove the water that is bound to the product, the temperature is slowly increased. It will be 100% dried afterwards. 

4. Backfill & Stoppering

Once the product has fully dried, sterile air is backfilled into both chambers to remove the vacuum and restore normal pressure. The freeze dryer then collapses the shelves to fully insert the stoppers.