Continuously operated crystallizer processes

For a complete description of the crystal size distribution (CSD) in a continuously operated crystallizer it is necessary to quantify the nucleation and growth processes and to apply the three conservation laws of mass, energy and crystal population. The importance of the population balance, in which all particles must be accounted for, has been a central feature in the pioneering work of Randolph and Larson (1962, 1988). 

A crystallization process has to be designed to meet a number of requirements, for example, particle properties such as particle size and purity. As concerns the purification, a continuously operated crystallization has to deal with the accumulation of impurities in the mother liquor. The drain point for these impurities has to be carefully chosen. It is one of the most underestimated aspect of the process design activity and the source of many errors. Moreover, the process yield is strongly connected with the planning of the process drain points, as is the specific energy consumption and, thus, the success of the process. However, die separation attribute of the unit operation crystallization may not be the best available and one should remain open for competing alternatives. That could be recommendable, for example, in cases of solid solutions, especially with distribution coefficients close to 1, which are not feasible to separate by crystallization at all. 

One, the CLEAR process, was investigated by Duval Corporation near Tucson, Arizona (29). It involves leaching copper concentrated with a metal chloride solution, separation of the copper by electrolysis, and regeneration of the leach solution in a continuous process carried out in a closed system. Elemental sulfur is recovered. Not far from the Duval plant, Cypms Mines Corporation operated a process known as Cymet. Sulfide concentrates undergo a two-step chloride solution leaching and are crystallized to obtain cuprous chloride crystals. Elemental sulfur is removed during this stage of the process. 

In batch operations, mixing takes place until a desired composition or concentration of chemical products or solids/crystals is achieved. For continuous operation, the feed, intermediate, and exit streams will not necessarily be of the same composition, but the objective is for the end/exit stream to be of constant composition as a result of the blending, mixing, chemical reaction, solids suspension, gas dispension, or other operations of the process. Perfect mixing is rarely totally achieved, but represents the instantaneous conversion of the feed to the final bulk and exit composition (see Figure 5-26). 

It should therefore not be surprising that for relatively small-scale operations involving solids handling within the fine and intermediate chemicals industry, batch operation is preferred. Similarly, continuous processes that involve precipitation or crystallization, a common unit operation in fine chemicals, are rare. Small-scale examples are known, for instance, a continuous crystallization process was used by Bristol-Myres Squibb in order to improve dissolution rates and bioavailability of the product [12]. The above does indicate that not all process or parts thereof are suited for conversion from B2C, given the current technology. 

High or ultrahigh product purity is obtained with many of the melt-purification processes. Table 20-1 compares the product quality and product form that are produced from several of these operations. Zone refining can produce very pure material when operated in a batch mode however, other melt crystallization techniques also provide high purity and become attractive if continuous nigh-capacity processing is desired. Comparison of the features of melt crystallization and distillation are shown on Table 20-2. 

Union Carbide (34) and in particular Dow adopted the continuous mass polymerization process. Credit goes to Dow (35) for improving the old BASF process in such a way that good quality impact-resistant polystyrenes became accessible. The result was that impact-resistant polystyrene outstripped unmodified crystal polystyrene. Today, some 60% of polystyrene is of the impact-resistant type. The technical improvement involved numerous details it was necessary to learn how to handle highly viscous polymer melts, how to construct reactors for optimum removal of the reaction heat, how to remove residual monomer and solvents, and how to convey and meter melts and mix them with auxiliaries (antioxidants, antistatics, mold-release agents and colorants). All this was necessary to obtain not only an efficiently operating process but also uniform quality products differentiated to meet the requirements of various fields of application. In the meantime this process has attained technical maturity over the years it has been modified a number of times (Shell in 1966 (36), BASF in 1968 (37), Granada Plastics in 1970 (38) and Monsanto in 1975 (39)) but the basic concept has been retained. 

The design and operation of industrial crystallizers is where developments in the laboratory are confirmed and their practical significance determined. In recent years, crystallization processes involving specialty chemicals and pharmaceuticals have increased. This has led increased interest in batch crystallization operation, optimization and desigrt At the same time, the advent of powerful computers and their routine avaUabilily has stimulated interest in the area of on-line control of crystallization process (both batch and continuous). Progress in batch crystallization is surrunarized in a number of recent papers and reviews 173-801. In this section I will discuss two areas which I think will have an impact in the next decade. 

A continuous crystallization process ultimately reaches a steady state, in which the rates of nucleation and growth are constant with time. For a given set of operating conditions, crystal size distribution depends considerably upon the degree to which product classification is practiced. Figures 23 and 24 illustrate schematically the possible extremes between... 

Materials that have a tendency to grow readily on the walls of the crytallizer require periodic washout, and therefore an otherwise continuous operation would be interrupted once or even twice a week for the removal of these deposits. The impact that this contingency may have on the processing-equipment train ahead of the crystallizer must be considered. 

The sodium sulphate crystals were washed with a little water and again filtered, the crystals being dumped out and the wash going to join the mother liquor. This mixed liquor was concentrated to the proper point to receive more ammonium sulphate and another charge of sodium nitrate, and the operation continued. The crystallizing rooms contained some miles of pans and had the largest air-conditioning plant ever erected. It has been stated that by the addition of a few units in one or two steps of the process the capacity could readily have been increased to 800,000 lb. per day. 

Crystal growth is a layer-by-layer process, and the retention time required in most commercial equipment to produce crystals of the size normally desired is often on the order of 2 to 6 h. Growth rates are usually limited to less than 1 to 2 pm/min. On the other hand, nucle-ation in a supersaturated solution can be generated in a fraction of a second. The influence of any upsets in operating conditions, in terms of the excess nuclei produced, is very short-term in comparison with the total growth period of the product removed from the crystallizer. A worst-case scenario for batch or continuous operation occurs when the explosion of nuclei is so severe that it is impossible to grow an acceptable crystal size distribution, requiring redesolution or washout of the system. In a practical sense, this means that steadiness of operation is much more important in crystallization equipment than it is in many other types of process equipment. 

Many operations—spills, emissions to the atmosphere, contamination of waste-water streams, and disposal of wastes—release solvents and other compounds to the environment. Controlling emissions is particularly important for continued operations on a manufacturing scale. To decrease emissions, reactions may be run at lower temperatures, or higher-boiling solvents may be chosen. Sometimes solvents are avoided if they are difficult to remove or if the chemist anticipates that the presence of this solvent will cause down-stream processing difficulties. DMSO can be considered one of these solvents Multiple extractions with HzO may be necessary to satisfactorily remove DMSO, and small amounts of residual DMSO may adversely affect the crystallization of the product. 

It should be noted that development of the crystallization processes in most of the examples presented in later chapters occurred before the availability of many of the online measurement and control methods that are now available. Utilization of these methods would have aided both the process development and the manufacturing operations. The literature that describes these methods—for example, feedback control of supersaturation for crystallization (Nonoyama et al. 2006 Zhou et al. 2006)—is now extensive, and the instrumentation to carry out the measurements and control continues to be improved. 

The difference between batch, semibatch, continuous, and semicontinuous processing was discussed in Chapter 1. Continuous processes are characterized by parameters which may be geographically distributed within the system but are unchanging with time. Continuous crystallizers are in common use throughout the chemical process industries, but are less so in the pharmaceutical and fine chemical industries because of the typically smaller amounts to be processed. This section on continuous cooling crystallization will discuss continuous operation and point out the differences from batch/semibatch operation described above. It will also illustrate some strategies and equipment types used for these operations. 

Example 7-6 illustrates the applicability of good crystallization practice to achieve continuous production of large-volume pharmaceutical compounds. It also illustrates a crystallization process that is inherently unfeasible by any method other than continuous operation. When carried out using fluidized bed crystallizers, ultrasonic crystal disraption is used, even at factory scale, to maintain a steady-state population of seed particles in this all-growth system. 

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