What is Freeze Drying?

Lyophilization and freeze drying are considered synonymous.

Freeze Drying is a water removal process typically used to preserve perishable materials, to extend shelf life or make the material more convenient for transport. Freeze-drying works by freezing the material, then reducing the pressure and adding heat to allow the frozen water in the material to sublimate.

There are 3 stages to freeze drying:

The freezing phase can be considered as the most critical step in the freeze drying process.  Proper freeze drying can reduce drying times by 30%.

There are various methods to freezing the product.  Freezing can be done in a freezer, a chilled bath (shell freezer) or on a shelf in the freeze dryer. Cooling the material below its triple point ensures that sublimation rather than melting will occur.  This preserves its physical form.

Large ice crystals are easiest to freeze dry. Slow freezing or annealing will produce larger ice crystals.  For Biological materials, if the crystals are too large, they may break the cell walls which will offer less than favorable freeze drying results.  To prevent this from happening, the freezing is done rapidly.  For materials that tend to precipitate, Annealing can be used.  Fast freezing, then raise the product temperature to allow the crystals to grow.

Primary drying (sublimation) is the phase in which the pressure is lowered and heat is added to the material in order for the water to sublimate. The vacuum speeds sublimation. The cold condenser provides a surface for the water vapor to adhere and solidify. The condenser also protects the vacuum pump from the water vapor.  About 95% of the water in the material is removed in this phase. Primary drying can be a slow process. Too much heat can alter the structure of the material.

During Secondary drying (adsorption), the ionically-bound water molecules are removed.  By raising the temperature higher than in the primary drying phase, the bonds are broken between the material and the water molecules.  Freeze dried materials retain a porous structure.  After the freeze-drying process is complete, the vacuum can be broken with an inert gas before the material is sealed.  Most materials can be dried to 1-5% residual moisture.

 


 

Problems To Avoid During Freeze Drying

  • Heating the product too high in temperature can cause melt-back or product collapse
  • Condenser overload caused by too much vapor hitting the condenser.
    • Too much vapor creation
    • Too much surface area
    • Too small a condenser area
    • Insufficient refrigeration
  • Vapor choking – the vapor is produced at a rate faster than it can get through the vapor port, the port between the product chamber and the condenser,  creating an increase in chamber pressure.

Important Terms

Eutectic Point or Eutectic Temperature – is the point at which the product only exists in the solid phase, representing the minimum melting temperature.
Not all products have a eutectic point or there may be multiple eutectic points

Critical Temperature – during freeze drying, the maximum temperature of the product before it’s quality degrades by melt-back or collapse

Crystalline – the material forms crystals when frozen

  • Has a Eutectic Point or multiple eutectic pts
  • Fast freezing creates small crystals which are hard to dry
  • Annealing can help form bigger crystals

 Amorphous – Multi-component mixtures which do not crystallize and do not have a eutectic point. They turn into a ‘glass’.

  • Does not have a Eutectic Point
  • For Amorphous materials freeze drying needs to be performed below the glass transition temperature

Collapse – The point at which the product softens to the extent that it can no longer support its own structure.

Why is it a problem?

  • Loss of physical structure
  • Incomplete drying
  • Decreased solubility
  • Lots of ablation (splat)

FREEZE DRYING CYCLE

  • Sterilization
  • Freeze Drying Cycle
    • Loading
    • Freezing
    • Primary Drying
    • Secondary Drying
    • Backfill
    • Stoppering
    • Aeration
    • Unloading
  • Defrosting
  • Cleaning/CIP
  • Filter Integrity Testing
  • Leak Test