* * * INSIGHT * * *
The Effect of the Mushy System
It is a common occurrence that when visiting a company, someone like a QA or Production Manager will show me some of their “lyophilized” products. I tend to shutter when they utter that word “lyophilized” for fear there might not be any rational to support that use of the term to describe their product (see INSIGHT Vol. 2 No. 1). I try my best to keep a straight face when I am told that the product has to be “lyophilized” because they dried it in a lyophilizer. But that is another story and I shall perhaps return to that theme in some future INSIGHT.
There may be a time when I will look at a cake and say it looks fine to me and give it back to my concerned host. They will often for some reason repeat my words, perhaps just to make sure they understood what I had said. No doubt they are pleased with my response but they still have an element of doubt. Maybe I didn’t look at it close enough or examined it too quickly, so they will now ask the real question that they should have asked me when they gave me the vial in the first place.
“What about that little peak in the middle of the cake?” is the general reply.
“Yes, I see that peak - so what?” is my reply - I admit I can be a bit frustrating at times but it is at times like these that I just can’t seem to resist the urge.
“Well is it a defect or not?” comes the primary concern of the individual.
“No”, is my reply “Its formation is a result of a mushy system.”
“Never heard of a “mushy system” is the not unexpected reply.
So it will be the objective of this INSIGHT to first describe how a “mushy system” is formed and how formation of that system can lead to a cake having a small peak as one individual described it as a chimney.
During the initial freezing process all or a portion of the volume of the formulation will undergo supercooling. How large a volume that will supercool will be dependent on the degree of supercooling (see INSIGHT Vol. 2 No. 1) and shelf temperature the ramp rate of the shelf temperatures. In the region where supercooling has occurred there will be some lattice network of ice crystals. However, there will still be a liquid present so the supercooling will tend not to form a completely frozen system. This semi-frozen system or region is now referred to as “mush” [1].
If there is a liquid layer above the mush, then convection currents, as shown in Figure 1, which may form in the liquid and mushy region.
Figure 1 Convection currents in liquid and mush regions during freezing
It is a result of the convection currents that mush near the middle of the vial is forced upward to form a peak or chimney during the freezing process. Upon drying the frozen matrix one obtains a cake similar to that shown in Figure 2. It should be noted that there is no existing evidence that I know of that would even suggest that the composition of the peak is any different from that of any other portion of the cake. For that reason, the chimney did not result from a defective process rather than from “mush”.
Figure 2 A cake showing a chimney for from mush during the freezing process
Reference:
1. T. A. Jennings, Lyophilization - Introduction and Basic Principles, Interpharm Press,
Buffalo Grove, IL 1999.
Vol. 6 No. 4 April 2003
