Sublimation rate, freeze-drying

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... 

M. J. Pikal, S. Shah, D. Senior, and J. E. Lang, Physical chemistry of freeze drying measurement of sublimation rates of frozen aqueous solutions by a microbalance technique, J. Pharm. Sci., 72, 635-650 (1983). 

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 ... 

Thijssen, H. A. C., Rulkens, W. H. Effect of freezing rate on rate of sublimation and flavour retention in freeze-drying, p. 99-114. International Institute of Refrigeration (Comm. X, Lausanne, 1969)... 

Kobayashi, M. Vial variance of the sublimation rate in shelf freeze-drying. Paper 312. International Institute of Refrigeration (Montreal 1991)... 

With this information the maximum flow of energy can be estimated, which can be transported during freezing and main drying at a desired temperature difference between inlet and outlet temperature of the brine at the shelves, e. g. 2000 kj/h at a temperature difference of 3 °C. With this amount of energy approx. 0.7 kg ice could be sublimated per hour. (This estimate gives only the maximum possible sublimation-rate, whether it can be achieved or not depends from heat -and mass transfer conditions in the process (see Section 1.2.1 and Eq. (12)). 

Milnes and Mostaghaci [5.5] compared the consequences of different drying methods on the density, the sinter rate and micro structures of sublimated TiO-, suspensions. Evaporation of water in a micro-oven and by radiation heating leds to strongly bound agglomerates, while freeze drying resulted in softly bound secondary clusters. The freeze dried powder reached in 2 h of sintering 98 % of the theoretical density, while differently dried powders needed twice as much time and had a less fine microstructure. 

Sublimation temperatures are in the range of —10 to —40°C and corresponding vapor pressures of water are 2.6-0.13 mbar. Cabinet tray dryers are the most commonly used type. The trays are lifted out of contact with hot surfaces so the heat transfer is entirely by radiation. Loading of 2.5 lb/sqft is usual for foodstuffs. Drying capacity of shelf-type freeze dryers is 0.1-1.0kg/(hr)(m2 exposed surface). Another estimate is 0.5-1.61b/(hr)(sqft). The ice surface has been found to recede at the rate of 1 mm/hr. Freeze drying also is carried out to a limited extent in vacuum pans, vibrating conveyors, and fluidized beds. Condensers operate as low as —70°C. 

Tire rate of heat input to the frozen material is a function of the operating-vacuum method of heal transfer and the properties of ihe dried product. The operating vacuum determines the pressure difference and. in turn, the rate of mass transfer, which must be in balance with the rate of heat input. Otherwise, either melting will occur at the sublimation interface and the purpose of freeze-drying will be defeated or the sublimation temperature will decrease and the cost of processing will increase. 

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