The freezing of the product is one of the most important steps in the freeze drying cycle. For non-aseptic systems it is often a particle or impurity that services as the nucleation point allowing ice crystals to grow and the product to freeze. However, in aseptic systems of high purity it is not uncommon for the product to cool below its freezing temperature without ice crystal formation as there are no particulates available for ice nucleation. Substances that cool below the freezing temperature without becoming solid are referred to as sub cooled.
The degree of sub cooling will alter the ice crystal formation. The more the product sub cools, the smaller the resultant ice crystal structure. In freeze drying the size of the ice crystals plays a large role in determining the resistance of the product to drying. Long ice crystals promote low resistance to drying as they serve as channels for water vapor flow. Small, short crystals have higher resistance to vapor flow, and in general require slower drying rates.
Therefore a means to induce nucleation at a desired temperature promotes both a desired product characteristic but also promotes product heterogeneity. Without nucleation control the temperature at which each vial nucleates is a variable, with perhaps a 20 minute variation in time, and depending on the shelf temperature ramp rate, a corresponding variation in nucleation temperature, and resultant ice crystal structure.
There have been a number of means attempted on the laboratory scale to promote ice nucleation in freeze drying. One such technology is the use of an ice fog to promote nucleation by introducing a particulate to serve as the point of nucleation. The work of IMA LIFE along with its development partner Linde, has been to develop a means to produce and distribute an aseptic ice fog that nucleates all vials in a short time frame. This work has resulted in a novel means to produce and distribute a sterile ice fog that is applicable to laboratory, pilot, and product scale freeze dryers.