Discussion of Lyophilization or Freeze Drying in Trays

Discussion of Lyophilization or Freeze Drying in Trays
Thomas A. Jennings, Ph.D and Professor Ana Bacaoanu, Ph.D?.
May 2003
INSIGHT
No doubt that trays played a major role in the early days of lyophilization or freeze drying of products and continues to this day to be a major vessel in conducting these drying processes. Advances in freeze drying equipment, such as automatic loading, has to some degree reduced the need for the use of a tray. But this is only for products that are contained in vials or bottles and these advance systems are generally not used to freeze dry bulk materials. So for bulk products, we still must rely on a large container that we generally classify as a tray.
We intend in this INSIGHT to generally discuss the various materials used in fabricating trays that have been and continue to be used in the lyophilization or freeze drying of products. We will certainly point out the advantages, disadvantages and perhaps pose some new questions that we need to address. The trays that will be considered range from the traditional metal (stainless steel) to the more recently introduced Lyoguard(R) [1]. It should be clear to the reader that we have NO preference nor bias for or against any given type of tray but just wish to present an objective evaluation and make it clear that the selection of the tray will no doubt be very product dependent. So what may work for one product may not be applicable for another.
Composition: Trays are generally constructed out of three basic materials: metal, glass and plastic. As a result of the composition, each material will offer its own unique advantage and disadvantage.
Cold Roll Steel: To my knowledge, we know of no application today where this material is used in the fabrication of trays. Certainly, they would not be applicable in the food or health care industry because of the potential for rust contamination. However, we do not see any objections for their use in the manufacture of flowers and especially if they are either galvanized or electroplated. They would perhaps be easier to construct and may represent the least expensive of all the trays.
Stainless Steel: Trays made from stainless steel are perhaps the most commonly used trays in the lyophilization or freeze drying of products. They have numerous advantages which would include and not be limited to (a), they are corrosion resistant: (b), such trays can be depyrogenated at temperatures of 250 oC; (c), these trays are also durable and require no special handling and (d), they are reusable which in time can off-set their initial higher cost.
Aluminum: Aluminum trays are used in the freeze drying of bulk materials. They are certainly light weight when compared to the cold roll and stainless steel trays and are corrosion resistance. In addition, they can be anodized to give them a black surface which will increase their emissivity aid some what to the energy transfer resulting from radiant energy. They can be steam sterilized but we do not have any knowledge where they have been depyrogenated at 250 oC. Because aluminum is a relatively soft metal, one must be concerned with the effects of ?galling? (the removal of a surface layer generally in the form of a dust) should the product have to be removed by scraping.
Glass: Not all bulk products that can be lyophilized or freeze dried come into contact with a metal surface. As a result of their composition, these trays have similar advantages as those constructed from stainless steel, except they are by their very nature fragile and are subject to breakage that may occur over time from stress strains resulting from age and thermal shock.
Plastic Trays: Molded trays are useful in those applications not requiring high temperature depyrogenation. They tend to be (a), light weight when compared to the trays made from the previous materials,; (b), easy to clean and (c), quite durable and reusable
Lyoguard(R) Trays: While these trays can also be generally classified as plastic trays, they do have unique features and we felt they deserved their own category in this discussion. The basic reason being that they are covered with a membrane barrier that will allow a formulation prepared in an aseptic environment to be safely lyophilized or freeze dried in a non aseptic environment [1]. This feature is of major importance to those working with small freeze dryers which were not designed to withstand the harsh rigors of steam sterilization. However, given such an advantage there are also some disadvantages in that they tend not to be reusable and as a result of their unique feature to be more costly than those trays fabricate from the above materials.
Heat Transfer Properties: We have discussed the impact and need to understand heat transfer properties in previous INSIGHTs, e.g. (Vol. 5 No. 12 and Vol. 6 No. 1) and references [2-3]. In this INSIGHT, we shall just consider the role that composition and configuration of the tray can have on the heat transfer properties. In making such a comparison, allow me to make a number of assumptions and conditions so as to avoid possible confusion.
All the trays have the same general rectangular configuration and the only variables will be their total mass and thickness of bottom and walls.
That all trays contain the same volume of water.
In each case, the shelf-surface temperature is uniform and chamber pressures are equal.
The heat transfer rate (Qs) from shelf through the bottom wall of the tray is given by the Fourier`s law:
Neglecting the contact resistance between shelf and tray, the external surface temperature of the bottom of the tray is equal to that of the shelf.
One can consider that the temperature gradient has a single direction, perpendicular on the surface of the bottom of the tray. In the regions with a good contact area of the bottom of the tray with shelf surface there is also a good heat transfer. In the regions where the contact is not perfect it appears a new thermal impedance to heat transfer between shelf and bottom of the tray. This impedance is given by the existing medium (gas at very low pressure and low density), between shelf and bottom of the tray. and will increase as the pressure is lowered. Consequently, the heat transfer is reduced in these regions. But the heat transfer is more complicated. To the normal temperature gradient (perpendicular on shelf) new gradients can be added on the other directions, anywhere a temperature difference exists between different points (position).
Cold Roll Steel: For purposes of this INSIGHT we shall assume that the thickness of the walls and bottom are 0.051 inches (1.2 mm). The thermal conductivity (lambda) cold roll steel is about 45.6 W/(m oC) and the specific heat over the normal temperature range for lyophilization or freeze drying is 0.4609 kJ( kg? oC) [4]. Now it is well known that it is rather difficult to fabricate a steel tray in which the bottom surface is in full thermal contact with the shelf surface. Thus one can only expect a fraction of the bottom surface to be in direct contact with the shelf surface. In the worse cases, contact may be only at three corners or rest on a small area in the middle. For our comparative model ( which we will use for all trays except for the Lyoguard(R) trays) we will assume only 10% of the bottom surface will be in contact with the shelf. Given that (Ts - Tp), is 1 oC, the value of Qs now becomes 3.875?A (in kW). One can see that as A increases, the thermal
conductivity across the tray becomes more of a real factor. Energy will flow from the edges towards the center so one can expect a temperature gradient across the bottom of the tray as the temperature of the shelf is varied. This temperature gradient will be directly proportional to the thickness of the tray and inversely proportional to the length of the conduction path so the configuration of the tray is an important consideration.
If the height of the walls of the tray are 1 inch (2.54 cm) and the density of the steel is taken as 7850 kg/m3 [4], the mass of the tray is defined as ?abd?, where ?a? is the width of the tray and ?b? is the tray length in m such that the mass (M) can be expressed as:
M = Vm ? 7850 (kg) (4)
where Vm is defined as the volume of metal used to fabricate the tray.
The amount of energy (Q) required just to change the tray temperature by 1 oC (DT =1) can be expressed as :
Q = M? cp ? Delta T = M ?0.460911 ?1 = 0.46091? M(kJ)(5)
Stainless Steel: Given the same thickness as the cold roll steel, the thermal conductivity (lambda) is given as 15.11 W/(m oC). A comparison of the thermal conductivity shows that the cold roll steel is three (3) times more thermally conductive than that of the stainless steel. For a tray of the same dimensions as that of the cold roll steel and with only 10% of the bottom of the tray in contact with the shelves, the heat transfer rate (Q) between the shelf surface and the tray when (Ts - Tp) is 1 oC will be 1.259?A (kW). As a result, for a tray constructed out of stainless steel, it will only transfer 33 % of the energy of that for the cold rolled tray.
The specific heat of the 304 stainless steel is 0.5028 kJ/(kg oC), the amount of energy one [5] while the density is given as being 8020 kg/m3 . The mass (M) of the tray having the same dimensions as above, will then be given as:
M = Vm ?8020 ( kg)(6)
The amount of energy (Q) required just to change the tray temperature by 1 oC can be expressed as:
Q = M? cp ? DeltaT = M ?0.5028 ?1 (kJ) (7)
Since the mass of the tray will be greater than that of the cold roll steel, the amount of energy to change the temperature of the tray by 1 oC will be more than that for the cold roll steel.
Aluminum: Aluminum trays (alloy 2017) having the same thickness as the cold roll steel, the thermal conductivity (lambda) is given as about 104 W/(m oC). A comparison of the thermal conductivity shows that this alloy of alum