Freeze-drying heat-transfer

Feed gas for carbon monoxide recovery is pretreated to remove carbon dioxide and water. The gas must be dried to remove all traces of moisture. Both carbon dioxide and water will freeze and heat transfer will be impaired at cryogenic temperatures. The feed gas is also compressed to the pressure required for the partial condensation of carbon monoxide at the temperatures that can be reached with the refrigeration system available. Typically, this is between 350 and 500 psig. The operating temperatures are approximately — 160 F to — 200°F. 

In thermal separation processes sublimation is of practical interest in freeze or sublimation drying. Heat transfer into the system causes moisture to sublime directly from the frozen solid into the vapor phase (see Chapter 5.10). Desublimation is important for the separation of gas mixtures if components of the mixture change directly from the gas into the solid state when heat is removed, these components can be sepa-... 

In the first example, procaine penicillin, an aqueous vehicle containing the soluble components (such as lecithin, sodium citrate, povidone, and polyoxyethylene sorbitan monooleate) is filtered through a 0.22 pm membrane filter, heat sterilized, and transferred into a presterilized mixing-filling tank. The sterile antibiotic powder, which has previously been produced by freeze-drying, sterile crystallization, or spray-drying, is aseptically added to the sterile solution while mixing. After all tests have been completed on the bulk formulation, it is aseptically filled. 

In freeze-drying, a solution is filled into vials, a special slotted stopper is partially inserted into the neck of the vial (Fig. 3), and trays of filled vials are transferred to the freeze-dryer. The solution is frozen by circulation of a fluid, such as silicone oil, at a temperature in the range of — 35 to about — 45°C through internal channels in the shelf assembly. When the product has solidified sufficiently, the pressure in the freeze-dry chamber is reduced to a pressure less that the vapor pressure of ice at the temperature of the product, and heat is applied to the... 

In addition to the effects of formulation factors on freeze-drying behavior, it is important for the pharmaceutical scientist to understand basic principles of heat and mass transfer in freeze-drying [29,30]. Because of the high heat input required for sublimation (670 cal/g), transfer of heat from the heated shelf to the sublimation front is often the rate-limiting step in the coupled heat... 

S. L. Nail, The effect of chamber pressure on heat transfer in the freeze drying of parenteral solutions, J. Parenter. Drug Assoc., 34, 358-368 (1980). 

Heat and Mass Transfer in Low Pressure Gases Applications to Freeze Drying... 

In pharmaceutical systems, both heat and mass transfer are involved whenever a phase change occurs. Lyophilization (freeze-drying) depends on the solid-vapor phase transition of water induced by the addition of thermal energy to a frozen sample in a controlled manner. Lyophilization is described in detail in Chapter 16. Similarly, the adsorption of water vapor by pharmaceutical solids liberates the heat of condensation, as discussed in Chapter 17. 

The systematic description of heat and mass transfer applications in freeze drying is considered in this section. Mechanistic interpretations are discussed in the fol-... 

Barriers to heat transfer produce corresponding temperature differences in a freeze-drying system, the actual temperature profile depending upon the rate of sublimation, the chamber pressure, and the container system as well as the characteristics of the freeze dryer employed. An experimental temperature profile is shown in Figure 5 for a system where vials were placed in an aluminum tray with a flat 5 mm thick bottom and a tray lid containing open channels for escape of water vapor. Here, heat transfer is determined by four barriers ... 

As the pressure increases from low values, the pressure-dependent term in the denominator of Eq. (101) becomes significant, and the heat transfer is reduced from what is predicted from the free molecular flow heat transfer equation. Physically, this reduction in heat flow is a result of gas-gas collisions interfering with direct energy transfer between the gas molecules and the surfaces. If we use the heat conductivity parameters for water vapor and assume that the energy accommodation coefficient is unity, (aA0/X)dP — 150 I d cm- Thus, at a typical pressure for freeze drying of 0.1 torr, this term is unity at d 0.7 mm. Thus, gas-gas collisions reduce free molecular flow heat transfer by at least a factor of 2 for surfaces separated by less than 1 mm. Most heat transfer processes in freeze drying involve separation distances of at least a few tenths of a millimeter, so transition flow heat transfer is the most important mode of heat transfer through the gas. 

V. MECHANISMS OF HEAT AND MASS TRANSFER IN FREEZE DRYING... 

Two special cases of radiative heat transfer which are applicable to heat transfer in freeze drying are illustrated by Figure 32. Heat transfer between body 1 and body 2 are illustrated for case I (Fig. 32a), where body 1 is of much greater area than body 2, Ai A2, and surrounds body 2. The freeze-drying example is heat exchange between the top of the vial (body 2) and the freeze dryer shelf... 

Figure 32 Two special cases of radiation heat transfer with importance to freeze-drying applications, (a) Case I Body 1 is the surroundings. (b) Case II Bodies 1 and 2 are of equal areas, and e = 1 for body 2.

MJ Pikal. Use of laboratory data in freeze drying process design Heat and mass transfer coefficients and the computer simulation of freeze drying. J Parenter Sci Tech-nol 39 115-138, 1985. 

MJ Pikal, ML Roy, S Shah. Mass and heat transfer in vial freeze-drying of pharmaceutical Role of the vial. J Pharm Sci 73 1224-1237, 1984. 

If the shelf and the tray are as planar as technically possible, the plot marked s = 0 applies. At 0.2 mbar, a heat transfer coefficient of approx. 85 kJ/m2 h °C can be achieved, rising by a factor of two at 1 mbar. In a well designed freeze drying plant with planar trays or vials a heat transfer coefficient of 160 kJ/h m2 °C at 0.9 mbar is possible (Fig. 1.59), while at a pressure of 0.45 mbar, approx. 120 kJ/h m2 °C (Table 1.9) is measured for the heat transfer coefficient A"tot. To sublimate 1 kg of ice per hour and m2 with a coefficient of... 

Oetjen, G. W., Eilenberg, H. J. Heat transfer during freeze-drying with moved particles, p. 19-35 International Institute of Refrigeration (Comm. X, Lausanne 1969)... 

Steinbach, G. Equations for the heat and mass transfer in freeze-drying of porous and non porous layers and bodiesm, p. 674 bis 683. International Institute of Refrigeration <1IR> (XIII, Washington 1971)... 

Kochs, M., Korber, Ch., Nunner, B., Fleschel, I. The influence of the freezing process on vapor transport during sublimation in vacuum-freeze-drying. Journal of Heat and Mass Transfer 34, p. 2395-2408, 1991... 

The thermal conductivity of ice and of dried products is relatively well known, but the surface heat transfer coefficient, Ksu during freezing and the total heat transfer coefficient K(ot during freeze-drying vary largely as described in the various chapters. Table 1.3 gives a survey of some data of interest in freeze-drying. 

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