Freeze-drying vacuum sublimation

Residual moisture is the low level of water, usually in the range of less than 1-3% (wt/wt), remaining in a freeze-dried product after the freeze-drying (vacuum sublimation) process [1-5] is complete. Nail [6] has described in-process methods to monitor the endpoint of freeze-drying using residual gas analysis, pressure rise, comparative pressure measurement, and product temperature measurement. Roy and Pikal [7] used an electronic moisture sensor inside the lyophilization chamber. Residual moisture [8] content is important in the final freeze-dried product because it affects the potency of the product, its long-term stability, and the official shelf life of the product. 

Cellulosic Membranes. The first asymmetric membrane for gas separation appeared in 1970 (Table II), and It was not surprising that this membrane was a modified CA membrane of the Loeb-Sourirajan type (17). Gelled CA membranes for water desalination must be stored wet In order to maintain their permeation performance. However, In gas permeation, wet, plasticized membranes tend to lose their properties with time due to plastic creep of the soft material under pressure and due to slow drying during which the microporous sublayer may collapse and thus increase the thickness of the dense skin-layer. Gantzel and Merten (17) dried CA membranes with an acetyl-content of 39.4% by quick-freezing and vacuum sublimation at... 

Sublimation of ice crystals to water vapor under a very high vacuum, about 67 Pa (0.5 mm Hg) or lower, removes the majority of the moisture from the granulated frozen extract particles. Heat input is controlled to assure a maximum product end point temperature below 49°C. Freeze drying takes significantly longer than spray drying and requires a greater capital investment. 

Freeze-drying, like all drying processes, is a method to separate liquid water from a wet solid product or from a solution or dispersion of given concentration. However, the main difference is that the liquid water is separated by solidification (i.e., the formation of ice crystals) and subsequent vacuum sublimation instead of evaporation. This allows a drying at subzero temperatures which can be advantageous in case of heat-sensitive products. There are two general applications... 

The next phase of the freeze-drying process entails the application of a vacuum to the system. When the vacuum is established, the temperature is increased, usually to temperatures slightly in excess of 0 °C. This promotes sublimation of the crystalline water, leaving behind a powdered cake of dried material. Once satisfactory drying has been achieved, the product container is sealed. 

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... 

Kemp, S. D. in Cremer, H. W. and Davies, T. (eds.) Chemical Engineering Practice, 6, (Butterworth, London, 1958) 567-600. Sublimation and vacuum freeze drying. 

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. 

Electron microscopy works under vacuum conditions because air absorbs electrons. For these reasons, wet samples cannot be analyzed by electron microscopy without previous dehydration, freezing, or freeze-drying due to the sublimation phenomena (Bache and Donald, 1998). 

Undercooling is the driving force in freeze drying. An aqueous salt solution is introduced dropwise into an immiscible liquid (hexane or a petroleum fraction such as kerosene) cooled below 243 K. The individual droplets are frozen instantaneously and the solid particles are decanted or filtered. The frozen particles are then sublimed in a vacuum to obtain a homogeneous powder of fairly uniform particle size. Important parameters in freeze drying are the final temperature of the salt solution and the cooling rate. These can be controlled to some extent, but only on a small scale. Hence the method is not very suited for large-scale manufacture of catalysts. 

Freeze-drying is a specialized process by which moisture is removed from a wet solid, usually placed on trays or in small containers, by sublimation under high-vacuum conditions. This is an energy-intensive procedure even compared with conventional drying processes but is used in a number of industries where heat causes damage to the product, reduces its yield, or... 

Subsequent to freeze stabilization, wet books can be thawed and air dried with or without interleaving or they can be vacuum dried in heated chambers (5). The moisture in frozen books can be sublimed by freeze drying (10) or removed by a vacuum/thaw/outgassing process (8), with microwave energy (6, 14), with dielectric energy (6), or by solvent extraction with or without vacuum assistance (5). 

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