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
Crystallization 53 7
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
Weight of 5. x 10 Crystals in Ib 2.0 spg. 5 Weig 2000 5.00010.000 20.000 -ass Weight 15 igure 2. Increase of weight with crystal si
540 Fermentation and Biochemical Engineering Handbook N t 0. 0 0 I/ I
proper orientation of the molecules, rather than by film diffusion to the surface; the crystal growth rate approaches zero order with increasing beretained in the crystallizer for a sufficient amount oftime to allow it to grow to the desired size The growth type crystallizers maintain the crystals in a fluidized bed (thereby providing both agitation and size classification of the crystals). The supersaturated solution flows through the fluidized bed and releases the supersaturation to the crystal surface Not all crystals will remain in the crystallizer the calculated retention time. This is only a statistical average. Since there will be a range of growth times, there will be a distribution of crystal sizes. The more narrow the range of actual retention times, the more narrow the crystal size distribution 3.0 CRYSTALLIZATION EQUIPMENT The type of equipment to be used in a crystallization process depends primarily upon the solubility characteristic of the solute. Solutions from fermentation processes can be classified as follows 1. Chemicals where a change in solution temperature has little effect on the solubility. An example is he thyl enetetramine as shown in Fig e supersaturated solution is produced by evaporation of the solvent. The equipment needed here is called an evaporative crystal lizer(see Fig. 4) 2. Chemicals, e.g, fumaric acid, which show only a moder- ate increase in solubility with increasing temperature. a combination of evaporation and cooling may be used to produce the supersaturated solution. Depending upon the yield required, this operation may be carried out in either a vacuum cooling crystallizer or an evaporative crystal- 3. Chemicals, e.g, adipic acid which show a large increase in solubility with increasing temperature. Cooling the solution can be an effective way to produce the supersatu rated solution, although a combination ofevaporation and poling can also be employed In addition to the two types of crystallizers mentioned above, a cooling crystallizer may be used(see Fig. 6)
Crystallization 541 proper orientation of the molecules, rather than by film diffusion to the surface; the crystal growth rate approaches zero order with increasing driving force. Since growth becomes a function of time only, the crystal must be retained in the crystallizer for a sufficient amount oftime to allow it togrow to the desired size. The growth type crystallizers maintain the crystals in a fluidized bed (thereby providing both agitation and size classification of the crystals). The supersaturated solution flows through the fluidized bed and releases the supersaturation to the crystal surface. Not all crystals will remain in the crystallizer the calculated retention time. This is only a statistical average. Since there will be a range of growth times, there will be a distribution of crystal sizes. The more narrow the range of actual retention times, the more narrow the crystal size distribution. 3.0 CRYSTALLIZATION EQUIPMENT The type of equipment to be used in a crystallization process depends primarily upon the solubility characteristic of the solute. Solutions from fermentation processes can be classified as follows: 1. Chemicals where a change in solution temperature has little effect on the solubility. An example is hexamethylenetetramine as shown in Fig. 3. The supersaturated solution is produced by evaporation of the solvent. The equipment needed here is called an evaporative crystallizer (see Fig. 4). 2. Chemicals, e.g., fumaric acid, which show only a moderate increase in solubility with increasing temperature. A combination of evaporation and cooling may be used to produce the supersaturated solution. Depending upon the yield required, this operation may be carried out in either a vacuum cooling crystallizer or an evaporative crystallizer (see Fig. 5). 3. Chemicals, e.g., adipic acid, which show a large increase in solubility with increasing temperature. Cooling the solution can be an effective way to produce the supersaturated solution, although a combination of evaporation and cooling can also be employed. In addition to the two types of crystallizers mentioned above, a cooling crystallizer may be used (see Fig. 6)
542 Fermentation and Biochemical Engineering Handbook AcID 1a20M4。560飞8090 TEMP2AT2E°c Figure 3. Effect of temperature rise on solubility in water WATE→st 2 OUTLET CONDENAE2 MESH SEPALA TOQ VAPOUZER OLATON PIPE TO HOT WELL EXcHANGER sUSPENDED C2(STALs CILCULATING PIMP Figure 4. Oslo evaporative crystall
542 Fermentation and Biochemical Engineering Handbook Figure 3. Effect of temperature rise on solubility in water. PEC cteWunnrG w Figure 4. Oslo evaporative crystallizer
Crystallization 543 T2→ Waice OTLET CONDENSED M5EP△R RQz日 ECILCUTION升P SUSMENSIO CHAMDEQ ODUCT OUTLET CIeCULATNG PUMP Figure 5. Oslo vacuum cooling crystallizer aSpEN 2ECIQCULATIdN APE FN三5 2MOA1 COOLING CIRCULATON PIPE CIRCUUATNC Figure 6. Oslo cooling crystallizer
Crystallization 543 Figure 5. Oslo vacuum cooling crystallizer. - eooua Figure 6. Oslo cooling crystalllzer
544 Fermentation and Biochemical Engineering Handbook One of the more important features of the Oslo type crystallizer is that the container for crystal growth has certain elements of design similar to all modes of operation(evaporative, vacuum cooling, cooling). In the crystal growth container a supersaturated solution of uniform temperature and concentration is conducted upward through a dense fluidized bed of crystals The crystals are kept fluidized by this upward flow of liquor. This results in a classifying action in the crystal growth container, which keeps the large crystals suspended in the bottom layer of the suspension and the smallest crystals in the top layer, with the intermediate sizes suspended between. If the process dictates the need for crystals being present throughout the system, the fluidized bed may be expanded to allow a portion of the crystals to overflow the crystal growth container into the circulation loop 3.1 Evaporative Crystallizer A properly designed crystallizer should result in reasonably long periods between clean outs, uniform crystal growth, and minimal flashing in the vaporization container to reduce entrainment. These objectives are attained by keeping supersaturation well below the upper limit of the metastable region in all parts of the crystallizer, and by maintaining a large fluidized suspension of crystals in the crystal growth container to provide sufficient surface for desupersaturation In the Oslo design this is accomplished by continuously mixing the feed liquor with a large amount of circulating mother liquor. The mixture is passed through a heat exchanger, where the heat required by the process is added by raising the temperature of the circulating mixture to a few degrees(3-6F) above the operating temperature of the crystallizer The heated solution is passed into the vaporization container where the temperature is lowered to the operating temperature by vaporization of an equivalent amount ofthe solvent. The supersaturated solution thus produced, flows down a central pipe and upward through the crystal growth container As the supersaturated liquor passes the fluidized crystals, the supersaturation is released to the surface of the crystals, allowing for uniform growth The now saturated mother liquor is passed out of the crystal growth container into the circulation loop where it is again mixed with fresh feed liquor and the cycle repeated In the crystal growth container a sufficient quantity of crystals is maintained in a fluidized bed to achieve almost complete release of supersatu ration. The individual crystals must be kept in constant motion, as they are by the fluidization, to prevent their growing together, but the motion must not
544 Fermentation and Biochemical Engineering Handbook One of the more important features of the Oslo type crystallizer is that the container for crystal growth has certain elements of design similar to all modes of operation (evaporative, vacuum cooling, cooling). In the crystal growth container a supersaturated solution of uniform temperature and concentration is conducted upward through a dense fluidized bed of crystals. The crystals are kept fluidized by this upward flow of liquor. This results in a classifjrlng action in the crystal growth container, which keeps the large crystals suspended in the bottom layer of the suspension and the smallest crystals in the top layer, with the intermediate sizes suspended between. If the process dictates the need for crystals being present throughout the system, the fluidized bed may be expanded to allow a portion of the crystals to overflow the crystal growth container into the circulation loop. 3.1 Evaporative Crystallizer A properly designed crystallizer should result in reasonably long periods between clean outs, uniform crystal growth, and minimal flashing in the vaporization container to reduce entrainment. These objectives are attained by keeping supersaturation well below the upper limit of the metastable region in all parts of the crystallizer, and by maintaining a large fluidized suspension of crystals in the crystal growth container to provide sufficient surface for desupersaturation. In the Oslo design this is accomplished by continuously mixing the feed liquor with a large amount ofcirculatingmother liquor. The mixture is passed through a heat exchanger, where the heat required by the process is added by raising the temperature of the circulating mixture to a few degrees (3-6'F) above the operating temperature of the crystallizer. The heated solution is passed into the vaporization container where the temperature is lowered to the operating temperature by vaporization of an equivalent amount ofthe solvent. The supersaturated solution thus produced, flows down a central pipe and upward through the crystal growth container. As the supersaturated liquor passes the fluidized crystals, the supersaturation is released to the surface of the crystals, allowing for uniform growth. The now saturated mother liquor is passed out of the crystal growth container into the circulation loop where it is again mixed with fresh feed liquor and the cycle repeated. In the crystal growth container a sufficient quantity of crystals is maintained in a fluidized bed to achieve almost complete release of supersaturation. The individual crystals must be kept in constant motion, as they are by the fluidization, to prevent their growing together, but the motion must not
