INSIGHT - Comments
Vol. 1 No. 10 Yes, You have no Eutectic
Thank you for the update I received from you. I am quite interested in a glossary of terms. I might mention that I am some what a beginner in this field. I have been employed as a freeze dryer operator for only 12 months now. Although I have learned quite a bit from text books and 'hands on work'.
I am still uncertain about certain definitions. I still do not fully understand the meaning of eutectic points. From what I gather eutectic point is related to heat transfer rate, but I don't understand how this is employed in a product to be dried. How exactly eutectic points affect the product. I do understand the basic principles of freeze drying though, the need for pre-freezing followed by primary and secondary drying and the process of sublimation.
I would certainly appreciate any information you could pass on.
Kimberly Hoeschle
Sydney Australia
kregg@ozemail.com.au
Reponse by T.A. Jennings, Ph.D.
You stated in your recent e-mail message that “I still do not fully understand the meaning of eutectic points.” The term eutectic can be confusing and, if you are having trouble with understanding its meaning, there are no doubt others who feel the same way. Let me try to explain the term to you. It will be helpful if you have Figure 1 from INSIGHT Vol. 1 No. 10 handy so that you can follow my train of thought.
First of all let us make up an isotonic solution of sodium chloride (NaCl), i.e., 0.9% NaCl wt/wt. Such a solution would contain 99.1% wt/wt water. At ambient temperature [T greater than T(1)] shown in Figure 1, there will only be one phase present, i.e, solution. Let us now cool down the solution to where T is lower than T(1) and we reach the solid line that connects points T(1) and E. At this point some ice will form. We continue to lower the temperature and more ice is formed. Now by forming ice we are in essence removing water from the solution so the NaCl concentration in the solution increases. By lowering the temperature still further we will finally approach point E (see Figure 1). At this point the temperature could be -20 oC and we will have ice and a salt solution that is approaching 23% wt/wt. So by lowering the temperature and forming ice we have changed the concentration of NaCl in the solution from 0.9% wt/wt to nearly 23% wt/wt. If we now lower the temperature to -21.1 oC, the concentration of the solution will reach 23% wt/wt and crystals of NaCl × 2H2O will form in the solution. With the formation of NaCl × 2H2O we have reached the eutectic point for sodium chloride. If we had selected potassium chloride (KCl), the eutectic would have occurred at -11 oC. So each salt will have its own eutectic temperature.
Now returning to our example of NaCl, when we reach the eutectic point the removal of more energy from the sample will not lower the temperature but just cause the formation of more ice and NaCl × 2H2O. As long as there is solution present, the temperature will remain fixed at -21.1 oC and the concentration of the solution will be 23% NaCl wt/wt. (We say that under these condition the number of degrees of freedom is 0.) Only after there is no longer any solution present can the temperature be made lower than -21.1 oC.
Now the reverse will be true for warming our sample. At temperatures lower than -21.1 oC we will have no solution present and we will have a system of ice crystals that have between them (the interstitial region) a mixture of NaCl × 2H2O and ice crystals that have a composition of 23% wt/wt NaCl and 77% wt/wt water. Upon warming the system to -21.1 oC, this mixture of NaCl × 2H2O and ice crystals will suddenly melt. Only after all of the mixture has melted can the temperature of the system be increased to temperatures greater than -21.1 oC.
Now if we were attempting to lyophilize NaCl, we would have to maintain the product temperature below -21.1 oC during the primary drying . If the temperature were to increase to -21.1 oC or higher, there would be a solution in between the ice crystals and one would not obtain a cake that would have the same volume as that of the frozen system but a mass of NaCl on the bottom. So eutectic points affect the lyophilization process by forming a system that has a very sharp melting temperature. At -22 oC we would have a solid interstitial region and at -20 oC a liquid interstitial region.
The point made by INSIGHT Vol 1 No. 10 is that for most products there is no eutectic mixture in the interstitial region but a glassy system where the melting temperature (referred to as the collapse temperature) is not sharp and well defined. Thus often one is looking for something that simply does not exist.
