Conceptual Design of Crystallization Processes

Christianto Wibowo, Ka Ming Ng

• Publisher: De Gruyter
• Year: 2020
• ISBN:
  9781501513527
• Edition: 1
• Topic: Technik & Maschinenbau
• Subtopic: Chemie- & Biochemietechnik

The book presents, in a unified manner, various crystallization design methods. It discusses in detail the geometric framework for representing complex phase behavior involving multiple solutes, enantiomers, hydrates, compounds, polymorphs, and solid solutions through visualization of high-dimensional phase diagrams. It also describes how the impact of transport processes is accounted for using kinetically controlled process paths.

1 Introduction

1.1 Crystallization in the Chemical Processing Industries

Crystallization is an important separation technique in the chemical processing industries for various reasons. First, it is able to produce a high-purity final product in solid form. Most separation techniques such as extraction and absorption simply transfer the chemical product from one phase to another. Second, crystallization can be scaled up for large-scale production while techniques such as electrophoresis and chromatography are only suitable for the separation of chemicals in small quantity. Third, it can separate organics, biochemicals, inorganics, and polymers that are sensitive to heat or have high boiling point. This is important, as chemical companies, in search of a higher profit margin, shift their focus from commodity to specialty chemicals that often cannot be separated by distillation. Fourth, like distillation, crystallization allows the complete separation of a multicomponent mixture of chemicals even if the system exhibits complex phase behavior. In distillation, this is achieved by bypassing the azeotropes using extractive distillation, azeotropic distillation, and so on. In crystallization, this is accomplished by bypassing the eutectics using fractional crystallization, extractive crystallization, and so on.

Table 1.1 lists a number of examples that illustrate the wide range of applications of crystallization in the chemical processing industries. The earliest applications of crystallization mostly deal with the recovery of inorganic salts from solution by evaporating water. The harvesting of salt from seawater has been practiced since antiquity [1]. Similarly, the separation of potash as a fertilizer from sodium chloride has been a major industrial operation to this day. Lithium carbonate, the major component for lithium batteries, is extracted from salt mines via crystallization from brines. Recently, there is a significant increase in the co-precipitation of compound salts such as Ni_0.6Co_0.2Mn_0.2(OH)₂ to meet the rising demand for cathode materials used in electric vehicle batteries. Crystallization is also widely used in the production of organic commodity chemicals such as p-xylene, bisphenol-A, terephthalic acid, and adipic acid, to separate the desired product from impurities and byproducts. Many specialty chemical and pharmaceutical products, such as diamondoids, azo dyes, monosodium glutamate, vitamin C, aspirin, and ibuprofen, are isolated in solid form by crystallization. In fact, most small molecule drugs (>90%) are delivered in crystalline form, and about 90% of newly developed active pharmaceutical ingredients are sparingly soluble in water [2].

Table 1.1:Application examples of crystallization in the chemical processing industries.

Market sector	Application	Reference
Inorganics	Recovery of potassium chloride from Lake Searles	Mumford [3]
	Isolation of potash (KCl) from sylvinite ore	Rajagopal et al. [4]
	Production of lithium carbonate from salt mine brines	Wilkomirsky [5]
	Production of precursors for NMC battery cathode material	Liang et al. [6]
Organics	Separation of p-xylene from m-xylene using extractive crystallization	Haines [7]
	Production of bisphenol-A using adduct crystallization	Moyers [8], Dermer [9]
	Reactive crystallization to produce technical grade terephthalic acid by liquid-phase air oxidation of p-xylene	Bernis et al. [10]
	Crystallization of adipic acid from a reaction mixture containing adipic, glutaric, and succinic acids with nitric acid and water as solvent	Oppenheim and Dickerson [11]
Specialty chemicals	Isolation of diamondoids from petroleum	Dahl et al. [12]
	Crystallization of azo dyes by salting-out from solution	Guccione [13]
	Crystallization of monosodium glutamate	Kawakita [14]
Pharmaceuticals	Purification of vitamin C (ascorbic acid)	Kuellmer [15]
	Production of aspirin	Thomas [16]
	Resolution of ibuprofen	Tung et al. [17]

In the design and development of crystallization processes, there are three requirements. First, the crystals have to meet product specifications such as size, shape, polymorphic form, and so on. If the particle size is too small, filtration may be difficult or take too long, and the presence of fines in the dried product can lead to dusting problem. Needle-shaped particles are often difficult to handle because they tend to break. Also, getting the right polymorphic form of a drug is extremely important, as different polymorphs can have different bioavailability. Second, the desired product has to be recovered in high purity and at low cost. Thus, it is important to design the crystallizer as well as its operating conditions to produce low impurity crystals at high per-pass yield. High purity crystals can be obtained by minimizing the amount of inclusion impurities within the crystals, which is influenced by particle size, growth rate, and agglomeration rate. Impurities adsorbed on the surface of the crystals can be washed away in the product recovery process, downstream of the crystallizer. High per-pass yield can be effected by setting the operating conditions in such a way that only the desired compound precipitates out. That is, the concentration of the desired chemical is set at its lowest value but above its saturation solubility, while the concentration of each of the remaining components is set at or above its saturation solubility. Third, due to the intense competition in the chemical processing industries, the design of the crystallization processes has to be of high quality and completed fast. These requirements can be met by examining crystallization from all scales, as explained here.

1.2 Crystallization as a Multiscale Design Problem

Figure 1.1 shows the length and timescales of various events/entities related to crystallization [18, 19]. The crystallizer size is of the order of meters. Fluid flow, crystal nucleation and growth, and chemical reaction occur at smaller length scales within the crystallizer. The size range of a single crystal spans about ten orders of magnitude. Semiconductor nanocrystals such as CdSe [20] and nanocrystal drugs [21] are just nanometers in size, while the potassium dihydrogen phosphate crystals created at Lawrence Livermore National Laboratory in California can reach a size of about a meter [22]. The time duration for an event in the crystallizer ranges from hours (such as residence time) to seconds (such as mixing time). The overlap signifies the fact that the interplay of mixing, transport, reaction kinetics, and nucleation and growth kinetics has to be taken into account in designing a crystallization process properly. Molecular considerations are critical for getting the desired particle shape and polymorphic form. The crystallizer is located within a chemical plant, which has a size of the order of hundreds of meters. The overlap between the plant and crystallizer signifies the need to properly design the crystallizer, in relation to its surrounding equipment. In fact, the crystallizer and its downstream filtration and washing system need to be designed in an integrated manner. Further up the length scale is the global enterprise. Decisions at the corporate level can influence whether a plant will be built and how a plant is designed.

Figure 1.1: The time and length scales of the tasks involved in the design of a crystal product (reprinted from [19] with permission from Elsevier).

This multiscale perspective provides a bird’s-eye view of what tasks need to be performed in the conceptual design of crystallization processes and the possibility of executing the tasks concurrently. The same approach has been applied to the design of reaction systems [23].

1.3 An Integrative Approach to Crystallization Process Design

Designing a crystallization process can be likened to building a house. As depicted in Figure 1.2, one begins with a sketch of the concept house, followed by building a strong foundation, before proceeding upwards. This foundation is the solid–liquid equilibrium (SLE) behavior of the system, which dictates the thermodynamic feasibility of the process. Obviously, SLE alone does not provide a complete picture. Selection of an appropriate cooling or evaporation profile, seeding policy, and crystallizer configuration – the equivalent of building the pillars and walls of the house – is next. Downstream processing units such as filters, washers, and dryers, which often cost more than the crystallizer and can be a source of serious operational problems, must be properly designed in conjunction with the crystallizer. Finally, process systems engineering techniques such as optimization, control, scheduling, and hazard and operability (HAZOP) analysis ...