Crystallization Stephen M. glasgow 1.0 INTRODUCTION Crystallization is one of the oldest methods known for recovering pure solids from a solution. The Chinese, for example, were using crystallization to recover common salt from water some 5000 years ago The perfection and beauty of the crystal which fascinated the early tribes now leads to a product of high purity and attractive appearance. By producing crystals of a uniform size, a product which has good flow, handling, packaging, and storage characteristics is obtained Crystallization is still often thought of as an art rather than a science While some of the aspects of art are required for control of an operating crystallizer, the discovery by miers of the metastable region of the supersatu rated state has made it possible to approach the growth of crystals to a uniform size in a scientific manner To produce pure crystalline solids in an efficient manner, the designer of crystallization equipment takes steps to ensure the control of I. The formation of a supersaturated solution 2. The appearance of crystal nuclei 3. The growth of the nuclei to the desired size 535
Crystallization Stephen M. Glasgow 1.0 INTRODUCTION Crystallization is one of the oldest methods known for recovering pure solids from a solution. The Chinese, for example, were using crystallization to recover common salt from water some 5000 years ago. The perfection and beauty of the crystal which fascinated the early tribes now leads to a product of high purity and attractive appearance. By producing crystals of a uniform size, a product which has good flow, handling, packaging, and storage characteristics is obtained. Crystallization is still often thought of as an art rather than a science. While some of the aspects of art are required for control of an operating crystallizer, the discovery by Miers of the metastable region of the supersaturated state has made it possible to approach the growth ofcrystals to aunifonn size in a scientific manner. To produce pure crystalline solids in an efficient manner, the designer of crystallization equipment takes steps to ensure the control of 1. The formation of a supersaturated solution 2. The appearance of crystal nuclei 3. The growth of the nuclei to the desired size 535
536 Fermentation and Biochemical Engineering handbook 2.0 THEORY The first consideration of the equipment designer is the control of the formation of a saturated solution. In order to do this, it is necessary to understand the field of supersaturation 2.1 Field of Supersaturation The solubility chart divides the field of the solution into two regions the subsaturated region where the solution will dissolve more of the solute at the existing conditions, and the supersaturated region Before Miers identified the metastable field, it was thought that a solution with a concentration of solute greater than the equilibrium amount iately form nuclei. Miers subsequent researchers determined that the field of supers Metastable region where solute in excess of the equilib rium concentration will deposit on existing crystals, but no new nuclei are formed Intermediate region-where solute in excess of the equilib rium concentration will deposit on existing crystals and new Labile region-where nuclei are formed spontaneously from a clear solution The equipment designer wishes to control the degreeof supersaturation of the solution in the metastable region when designing a batch crystallizer In this region, where growth takes place only on existing crystals, all crystals have the same growth time and a very uniform crystal size is obtained When designing a continuous crystallizer, the designer wishes to control the degree of supersaturation in the lower limits of the intermediate region. In continuous crystallization, it is necessary to replace each crystal removed from the process with a new nuclei. It is also necessary to provide some degree of crystal size classification if a uniform crystal size is to be Solutions of most organic chemicals can, as a general rule, attain a considerably higher degree of supersaturation than inorganic chemicals. The ormation of crystalline nuclei requires a definite orientation of the molecules
536 Fermentation and Biochemical Engineering Handbook 2.0 THEORY The first consideration of the equipment designer is the control of the formation of a saturated solution. In order to do this, it is necessary to understand the field of supersaturation. 2.1 Field of Supersaturation The solubility chart divides the field of the solution into two regions: the subsaturated region where the solution will dissolve more of the solute at the existing conditions, and the supersaturated region. Before Miers identified the metastable field, it was thought that a solution with a concentration of solute greater than the equilibrium amount would immediately form nuclei. Miers’ research and the findings of subsequent researchers determined that the field of supersaturation actually consists of at least three loosely identified regions (Fig. 1): Metastable region-where solute in excess of the equilibrium concentration will deposit on existing crystals, but no new nuclei are formed. Intermediate region-where solute in excess of the equilibrium concentration will deposit on existing crystals and new nuclei are formed. Labile region-where nuclei are formed spontaneously from a clear solution. The equipment designer wishes to control the degree of supersaturation of the solution in the metastable region when designing a batch crystallizer. In this region, where growth takes place only on existing crystals, all crystals have the same growth time and a very uniform crystal size is obtained. When designing a continuous crystallizer, the designer wishes to control the degree of supersaturation in the lower limits of the intermediate region. In continuous crystallization, it is necessary to replace each crystal removed from the process with a new nuclei. It is also necessary to provide some degree of crystal size classification if a uniform crystal size is to be obtained. Solutions of most organic chemicals can, as a general rule, attain a considerably higher degree of supersaturation than inorganic chemicals. The formation of crystalline nuclei requires a definite orientation ofthe molecules
Labile Saturation point Undersaturated Batch noe range Solubility Figure 1. 的
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538 Fermentation and Biochemical Engineering Handbook in the solution. This requires the proper orientation of several molecules at the moment of a random collision. Since the number of possible orientations increases with ing complexity of the molecule, considerably higher degrees of supersaturation can be obtained for solutions of chemicals with complex molecules 2.2 Formation of a Supersaturated Solution If a solution is to have only a slight degree of supersaturation, then a cyclic system in which large quantities ofliquor are supersaturated uniformly is required. The solution must then be brought back to saturation before feed liquor is allowed to enter the system and the mixture is again supersaturated in the next cycle The removal of the metastable supersaturation is a slow process. A large amount of crystal surface is required to allow for the large number of random collisions necessary to remove the supersaturation generated during the cycle. The proper orientation of both the molecules in solution and the molecule on the crystal surface is required for deposition, and the increased complexity of the molecule increases the number of collisions required for proper orientation If the supersaturation generated during the cycle is not completely removed, the level of supersaturation attained during the following cycle is increased. This increase from cycle to cycle will continue until the supersatu ration level of the solution exceeds the metastable region and enters the labile region,where spontaneous nucleation occurs. The occurrence of spontane ous nucleation means loss of control of crystal size Supersaturation is clearly the most important single consideration any crystallization process. By giving proper attention to the degree of supersaturation generated during each cycle and its proper release during the designstage, half the battle will be won. Supersaturation should be controlled by making certain only small changes in temperature and composition occur in the mass of mother liquor 2.3 Appearance of Crystalline nuclei Usually the crystallization equipment is charged with a clear feed solution. As this solution is saturated, it is important to control the increase in supersaturation as the labile region is approached. This is important since the formation of an excessive number of nuclei will cause a continuous crystallizer system to have an extremely long period before desired crystal
538 Fermentation and Biochemical Engineering Handbook in the solution. This requires the proper orientation of several molecules at the moment of a random collision. Since the number of possible orientations increases with increasing complexity of the molecule, considerably higher degrees of supersaturation can be obtained for solutions of chemicals with complex molecules. 2.2 Formation of a Supersaturated Solution If a solution is to have only a slight degree of supersaturation, then a cyclic system in which large quantities of liquor are supersaturated uniformly is required. The solution must then be brought back to saturation before feed liquor is allowed to enter the system and the mixture is again supersaturated in the next cycle. The removal of the metastable supersaturation is a slow process. A large amount of crystal surface is required to allow for the large number of random collisions necessary to remove the supersaturation generated during the cycle. The proper orientation of both the molecules in solution and the molecule on the crystal surface is required for deposition, and the increased complexity of the molecule increases the number of collisions required for proper orientation. If the supersaturation generated during the cycle is not completely removed, the level of supersaturation attained during the following cycle is increased. This increase from cycle to cycle will continue until the supersaturation level ofthe solution exceeds the metastable region and enters the labile region, where spontaneous nucleation occurs. The occurrence of spontaneous nucleation means loss of control of crystal size. Supersaturation is clearly the most important single consideration for any crystallization process. By giving proper attention to the degree of supersaturation generated during each cycle and its proper release during the design stage, half the battle will be won. Supersaturation should be controlled by making certain only small changes in temperature and composition occur in the mass of mother liquor. 2.3 Appearance of Crystalline Nuclei Usually the crystallization equipment is charged with a clear feed solution. As this solution is saturated, it is important to control the increase in supersaturation as the labile region is approached. This is important since the formation of an excessive number of nuclei will cause a continuous crystallizer system to have an extremely long period before desired crystal
Crystallization 539 size can be achieved and prevent a batch system from ever producing desired rystal size during that particular ru Once initial nucleation has been achieved successfully, the control of secondary nucleation becomes important. Since crystal growth is a surface phenomenon, each nuclei formed is available to absorb the supersaturation generated by the cycle. This means that only one nuclei is to be formed for each single crystal removed if a constant crystal size is to be maintained When an excessive number of nuclei are formed during operation of the crystallizer, the average size of the final product is reduced. As an example of this effect. one can assume the formation of 1 lb of 200 mesh nuclei Assuming that no further new nuclei are formed, this 1 lb would weigh 8 lbs if grown to 100 mesh crystals. Following this trend further, it is found that growth to 60 mesh crystals will result in 38 lbs; 14 mesh crystals would yield 7000 lbs(see Fig. 2) Secondary nucleation is constantly occurring. It occurs when a crystal collides with the vessel wall or with another crystal. To control this collision induced nucleation the number of crystals in the system must be controlled Increasing the local supersaturation into the labile region will also cause secondary nucleation. This occurs when there are local cold spots caused by radiation from the vessel wall, subcooling caused by subsurface boiling and build up of residual supersaturation in solutions with high viscosity and insufficient agitation. This calls attention to the need for insulation of the vessel, for control to ensure that boiling occurs at the liquid vapor interface, and for provision for sufficient agitation of the solution in the Mechanically induced nucleation can result from excessive agitation caused by an impeller sweeping through a solution in the metastable region of supersaturation or turbulence caused by violent boiling. By limiting the tip speed of a pump or agitator and limiting the escape velocity at the vapor liquid interface, this type of secondary nucleation can be minimized After the control of supersaturation, control of nuclei formation is the most important consideration in the design of crystallization equipment. If a constant number of crystals are maintained in the crystallizer, then a constant surface area for crystal growth will be available This will result in good control of product size 2. 4 Growth of Nuclei to Size As noted above, crystal growth is a surface phenomenon. Given sufficient agitation, the depositing of solute on the surface is controlled by
Crystallization 539 size can be achieved and prevent a batch system from ever producing desired crystal size during that particular run. Once initial nucleation has been achieved successfully, the control of secondary nucleation becomes important. Since crystal growth is a surface phenomenon, each nuclei formed is available to absorb the supersaturation generated by the cycle. This means that only one nuclei is to be formed for each single crystal removed if a constant crystal size is to be maintained. When an excessive number of nuclei are formed during operation ofthe crystallizer, the average size of the final product is reduced. As an example of this effect, one can assume the formation of 1 lb. of 200 mesh nuclei. Assuming that no further new nuclei are formed, this 1 lb would weigh 8 lbs. if grown to 100 mesh crystals. Following this trend further, it is found that growth to 60 mesh crystals will result in 38 lbs; 14 mesh crystals would yield 7000 lbs (see Fig. 2). Secondary nucleation is constantly occurring. It occurs when a crystal collides with the vessel wall or with another crystal. To control this collisioninduced nucleation the number of crystals in the system must be controlled. Increasing the local supersaturation into the labile region will also cause secondary nucleation. This occurs when there are local cold spots caused by radiation from the vessel wall, subcooling caused by subsurface boiling and build up of residual supersaturation in solutions with high viscosity and insufficient agitation. This calls attention to the need for insulation ofthe vessel, for control to ensure that boiling occurs at the liquidvapor interface, and for provision for sufficient agitation ofthe solution in the vessel. Mechanically induced nucleation can result from excessive agitation caused by an impeller sweeping through a solution in the metastable region of supersaturation or turbulence caused by violent boiling. By limiting the tip speed of a pump or agitator and limiting the escape velocity at the vaporliquid interface, this type of secondary nucleation can be minimized. After the control of supersaturation, control of nuclei formation is the most important consideration in the design of crystallization equipment. If a constant number of crystals are maintained in the crystallizer, then a constant surface area for crystal growth will be available. This will result in good control of product size. 2.4 Growth of Nuclei to Size As noted above, crystal growth is a surface phenomenon. Given sufficient agitation, the depositing of solute on the surface is controlled by