Industrial crystallization process

Thus, methods are now becoming available such that process systems can be designed to manufacture crystal products of desired chemical and physical properties and characteristics under optimal conditions. In this chapter, the essential features of methods for the analysis of particulate crystal formation and subsequent solid-liquid separation operations discussed in Chapters 3 and 4 will be recapitulated. The interaction between crystallization and downstream processing will be illustrated by practical examples and problems highlighted. Procedures for industrial crystallization process analysis, synthesis and optimization will then be considered and aspects of process simulation, control and sustainable manufacture reviewed. 

In practice, industrial crystallization processes are subject to a number of constraints, which tend to limit equipment selection. For example, since particle size and purity tend to be such important variables, equipment and operating conditions that induce minimum particle breakdown or achieve maximum crystal purity are normally desirable. 

Tavare, N.S., 1995. Industrial crystallization Process simulation, analysis and design. New York Plenum. 

The following list identifies the most important analytical techniques that are regularly used in the support of industrial crystallization process development and API solid phase characterization. 

Other areas. It is the purpose of this overview chapter to discuss areas which, in opinion, will be of greatest interest and potential use in the 1990 s. The list is by no means complete, however I believe that in the next decade much progress will be made in these areas and they will have a profound impact on industrial crystallization processes. 

There is a parameter necessary to describe the abrasion resistance of each crystalline substance. This abrasion resistance must be correlated with parameters of the power input devices such as pump or stirrer diameter or the stirrer tip speed. The abrasion resistance of the crystalline particles produced by secondary nucleation in industrial crystallization processes is therefore a physical property of the substance. So far there is no physical property known containing all information about this abrasion resis-... 

High growth rates (fim/min) can be achieved. The supersaturation required is less for the higher alcohol contents. The high growth rates in the absence of nucleation means that a practical industrial crystallization process can be developed to grow large fructose crystals. 

Fevotte, G. Calas, J. Puel, F. Hoff, C., Applications of NIR to monitoring and analyzing the solid state during industrial crystallization processes Int. J. Pharm. 2004, 273, 159-169. 

Additional processes that can be monitored using spectroscopic tools of PAC are crystallization and distillation. Crystallization is an important step in manufacture of many products including APIs. Tracking the process and production of material is more valuable than testing a final product to verify that the correct crystal structure has been attained. The use of acoustic spectroscopy 4 and NIR spectroscopy48 in industrial crystallization processes has been demonstrated and will be implemented more widely. Monitoring distillation processes, such as for solvent recovery, is another growing area of use of PAC. 

Tavare, N. S. (1995). Industrial Crystallization Process Simulation, Analysis and Design, Plenum, New York. 

A very important industrial crystallization process, which is the most common method used for the production of high-purity oriented single-crystalline semiconductor ingots, is the Czochralski method (Czochralski, 1918), named... 

Solid-liquid equilibrium phase diagrams play an important role in the design of industrial crystallization processes. The calculation of phase diagrams can be used to validate the activity coefficient model used for process simulation. 

This disadvantage is compensated by the ability to measure a wide size range from below 10 pm to above 3 mm and the fact that PSDs can be measured at very high concentrations (0.5 to >50 percent of volume) without dilution. This eliminates the risk of affecting the dispersion state and makes this method ideal for in-line monitoring of e.g., crystallizers (A. Pankewitz and H. Geers, LABO, In-line Crystal Size Distribution Analysis in Industrial Crystallization Processes by Ultrasonic Extinction, May 2000). 

PuEL, F., Fevotte, G. Klein, J. P. 2003a Simulation and analysis of industrial crystallization processes through multidimensional population balance equations. Part 1 a resolution algorithm based on the method of classes. Chemical Engineering Science 58, 3715-3727. 

Scale-Up of Industrial Crystallization Processes—Mission Impossible .311... 

SCALE-UP OF INDUSTRIAL CRYSTALLIZATION PROCESSES—MISSION IMPOSSIBLE ... 

YIELDS. In many industrial crystallization processes, the crystals and mother liquor are in contact long enough to reach equilibrium, and the mother liquor is saturated at the final temperature of the process. The yield of the process can then be calculated from the concentration of the original solution and the solubility at the final temperature. If appreciable evaporation occurs during the process, this must be known or estimated. 

In Equation 18.4, it is shown that filtrate flow rate strongly depends on particle size, which additionally influences the porosity of the filter cake. One can readily conclude that controlling both the particle size and PSD and avoiding the formation of fines (which may be triggered by unwanted nucleation events in an industrial crystallization process, for example) are vitally important. 

Virtually all industrial crystallization processes involve solutions. The development, design, and control of any of these processes involve knowledge of a number of the properties of the solution. This chapter will present and explain solutions and solution properties, and relate these properties to industrial crystallization operations. 

Accurate solubility data is a crucial part of the design, development, and operation of a crystallization process. When confronted with the need for accurate solubility data, it is often common to find that the data is not available for the solute at the conditions of interest. This is especially true for mixed and nonaqueous solvents, and for systems with more than one solute. In addition, most industrial crystallization processes involve solutions with impurities present. If it is desired to know the solubility of the solute in the actual working solution with all impurities present, it is very unlikely that data will be available in the literature. Methods for the calculation of solubility have been discussed previously. These can be quite useful, but often are not possible because of lack of adequate thermodynamic data. This means that the only method available to determine the needed information is solubility measurement. 

The habit of crystals obtained from an industrial crystallization process can have a major impact on a number of important properties relating to the slurry and the dry product. Crystal habit will affect the rheological properties of the suspension, the filtration or centrifugation efficiency, the bulk density of the solid, and the flow properties of the solid. The control of crystal habit (along with crystal size distribution) is, therefore, an important part of industrial crystallization processes. 

Crystallization from solution can be thought of as a two-step process. The first step is the phase separation, or birth," of new crystals. The second step is the growth of these crystals to larger sizes. These two processes are known as nucleation and crystal growth, respectively. Analysis of industrial crystallization processes requires knowledge of both nucleation and crystal growth. As was discussed in Chapter 1 of this volume, a supersaturated... 

The development and operation of industrial crystallization processes can be made significantly easier if some data on the kinetics of crystal growth are available. This information can be incorporated in process models, can be used in process and crystallizer design, and can shed light on the observed behavior of the system. 

Many industrial crystallization processes, by necessity, push crystal growth rates into a regime where defect formation becomes unavoidable and the routes for impurity incorporation are numerous. Since dislocations, inclusions, and other crystal lattice imperfections enhance the uptake of impurities during crystallization, achieving high purity crystals requires elimination of impurity incorporation and carry-over by both thermodynamic and non-thermodynamic mechanisms. Very generally, the impurity content in crystals can be considered as the sum of all of these contributions... 

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