SUBLIMATION TECHNIQUES - FREEZE DRYING

The theory of the sublimation process has been discussed in detail elsewhere41 the following describes the practical aspects of this technique which is applicable down to a few milligrams of material. 

With care a mixture may be fractioned by sublimation when the amount of sublimate formed at a particular temperature no longer seems to increase, the sublimation process should be stopped and the sublimate removed. The cleaned cold finger is then reintroduced and the sublimation is continued at a higher 

Another design is illustrated in Fig. 2.88 and may be purchased from appropriate suppliers or made to specification the sizes of the pot and of the cold finger are appropriate to the quantity of material to be sublimed, which may be as low as 20 mg. Frequently these assemblies, sometimes with slight modification, may be used for the high vacuum micro-distillation of viscous liquids (Section 2.28). 

For the sublimation of quantities of materials in the region of a few milligrams, the vacuum sublimation block supplied by Reichert-Jung is particularly suitable. This block is located on the hot-stage microscope (see p. 240), the sublimation chamber carefully evacuated, the temperature raised slowly, and the process of sublimation observed through the microscope. 

This process, frequently called lyophilisation, is necessary when water is to be removed from solutions containing heat-labile materials so that conventional distillation, even under reduced pressure, would cause extensive losses by decomposition. Examples are to be found in the removal of water from aqueous solutions of enzymes, polysaccharides, peptides, etc. In principle the aqueous solution is frozen in a suitable solid carbon dioxide freezing mixture (see Section 2.12), and the ice is sublimed off to leave a dry residue.42 

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In contrast to sublimation in freeze-drying, evaporation of a solvent is straightforward but may lead to less homogeneity for example, if a multicomponent solution is slowly evaporated, the various constituents crystallize nonuniformly. Thus, the goal of evaporative techniques is to break the solution into small droplets to minimize the volume over which segregation can take place as well as to maximize the surface area for evaporation and then evaporate the solvent as rapidly as possible to quench in the homogeneity of the solution. 

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). 

In addition, the sublimation of ice in freeze-drying, discussed in Chapter 16, has become an important operation particularly in the biological and food industries. The various industrial applications of sublimation techniques are discussed by several authors(3,40 95 96 97), and the principles underlying vaporisation and condensation and the techniques for growing crystals from the vapour phase 99-1 are also presented in the literature. 

Freeze drying is a technique for dehydrating substances at low temperatures, thereby avoiding the degradation that may accompany heating. The material to be dried is cooled to a temperature at which all of the water present turns to ice. The frozen substance is then placed in a vacuum chamber and may also be subjected to radiant or microwave heating the ice in the food sublimates, and the vapor is carried off by the vacuum pump. 

Distillation or sublimation techniques are commonly used to purify substances. For example, pure water as solvent is required in copious amounts the removal of many impurities is best accomplished by distillation. Iodine as a standard substance is best purified by sublimation. An important method for concentrating trace elements from water prior to analysis is by the technique of freeze-drying. 

The weak point of freeze-drying is its low productivity (expressed in number of cycles per year) and its cost. Pharmaceutical industry constraints, operation under vacuum, and the implementation of the sublimation phenomenon indeed require great investments, large energy consumption, and production delays far above those required with more classical dehydration techniques industrial... 

Lyophilization, also called freeze-drying, is the process of subliming a solvent, usually water, with the object of recovering the solid that remains after the solvent is removed. This technique is extensively used to recover heat- and oxygen-sensitive substances of natural origin, such as proteins, vitamins, nucleic acids, and other biochemicals from dilute aqueous solution. The aqueous solution of the substance to be lyophilized is usually... 

Freeze-drying, called lyophilization by the pharmaceutical industry, is a drying technique by which a product is solifidied by freezing and the solvent that contains it (usually water) is evaporated by sublimation (a chemical phenomenon) upon heating. The transformation of the solid phase into the gas phase takes place with neither the water nor the solvent passing through the liquid state. 

The freeze-drying method is one of solvent volatilization, but it differs from the common solvent evaporation techniques in that the solvent is sublimed from the solid state. A solution, prepared by means of soluble salts or by dissolving metals in acid, is frozen and the solid solvent, usually water in the form of ice, is sublimed away giving the dried salts. The process gives high surface area powders of excellent chemical homogeneity. 

If the phase change is solid to vapor, then this is a sublimation but the compound is lost. The preferred technique is solid to vapor back to solid, so the product can be collected. If the vapor is carried away from the sample surface as soon as it forms, so as to reduce the vapor pressure immediately above the sample, then this is called an entrainer sublimation, also in Chapter 7. If a liquid is solidified, changed to a vapor, and then to a solid, this is called freeze drying. This is discussed in Chapter 8. 

The whole principle of the freeze-drying process depends on the fact that water at temperatures below 0°C immediately transforms from the solid state of aggregation into the vaporous state. In other words, the technique is based on the sublimation properties of water. 

Probably the first comprehensive monograph on freeze-drying was published in 1949." It traces the early development of the technique, going back as far as 1813, when William Hyde Wollaston, in a lecture to the Royal Society, demonstrated the relation between vapour pressure and temperature, and the cooling effect of evaporation. Wollaston called the procedure sublimation , which he defined as the process in which a solid (ice) is converted into a gaseous state and then recondensed as a solid, thereby totally avoiding the intervention of a liquid state during the process. 

For the isolation of non-volatile water soluble compounds or biological materials from water, freeze drying is an effective technique. In this technique the water sample is frozen in a vial and the resulting ice sublimed away under vacuum. Organics are then solubilized in an organic solvent to separate them from the precipitated inorganic salts. 

Rosenkrantz (1957) has written one of the earlier articles on the utilization of fractionation procedures with infrared analysis and has listed several types of fractionation techniques chromatography, countercurrent distribution, preferential solvent extraction, sublimation, fractional crystallization, molecular distillation, dialysis, centrifugation, electrophoresis, diffusion, and freeze-drying. He has also given references to work in which these methods have been used to fractionate a large variety of biological compounds. Elvidge and Sammes (1966) have discussed many of the techniques mentioned above. 

Freeze-drying is one of the low-temperature drying techniques suitable for drying of highly heat-sensitive materials such as drugs, pharmaceutical, biological, and food products. Freeze-drying removes moisture captured inside the solids by sublimation of moisture from solid state (ice) to vapor state. 

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