1- The critical temperature of the product must be known. a. If a crystalline material, then the eutectic point is required b. If an amorphous material, the collapse temperature is required.
2- Freezing a. Ballistic freezing is typically performed at 0.5 to 1 /min. The product is held at temperature to freeze for 2 to 4 hours typically. b. Annealing - Some products require annealing, which is the process of freezing the product and then raising the temperature (while keeping the product frozen) so that the ice crystals can grow.
3- Vacuum level a. Most freeze drying is performed at 100 to 200 mT. Initially try 100 mT.
4- Shelf temperature a. The shelf temperature should be chosen to maintain a product temperature below its critical temperature. b. The product temperature is always below the shelf temperature due to sublimation. Therefore, the shelf temperature will be able to be driven above the critical product temperature. i. Example: If you have a -20C critical temperature, then try a shelf temperature 5 C higher, or -15C.
5- Primary Drying – removal of the unbound water – sublimation – good to 3-5% moisture content a. This is the most difficult part to determine for any product since it is dependent on many factors. Most freeze drying is complete within 24 hours. If the product has a low critical temperature (IE: < -20C), then the freeze drying cycle will be longer. Some cycles may be 72 hours for difficult products. b. If you product is in a straw, then the vapor will have a difficult time getting out. Therefore, the shelf temperature will have to be controlled close to the critical temperature and the duration of the run will be long. c. You may want to periodically remove some material to test it for moisture content using a Karl Fisher test setup.
6- Secondary Drying – removal of bound water – adsorption – can get to <1% moisture content a. Requires the shelf temperature to be raised above 20 C to provide the energy to break the ionic water bonds.