Scale-up of crystallizers

It can be concluded from the above that the following experiments on crystallization should be performed to produce data for decreasing the risk at scale-up of crystallizers ... 

As mentioned previously, scale-up of crystallization processes from the laboratory is far from straightforward. Various parameters need to be maintained to be as close to those used in the laboratory as possible in order to reproduce the results from the laboratory. For scale-up, supersolubility, agitation (and its effect on secondary nucleation throughout the vessel), fraction of solids in the slurry, seed number and sizes, contact time between growing crystals and liquid all need to be maintained. 

The use of variable-speed drives in pilot plant and manufacturing plant vessels is recommended for development and scale-up of crystallization processes. This capability provides the opportunity for critical experimentation at the pilot plant scale to determine the effect of impeller speed on PSD and other variables. On the manufacturing scale, the ability to change impeller speed is the most readily adjustable parameter for manipulation on scale-up. Modem variable-frequency drives provide an excellent means to vary speed over a wide range. The added cost of variable-speed capability is minimal compared to all other methods of changing mixing... 

Literally speaking, the scale-up of crystallization processes may frequently appear to be a mission impossible, or at least a demanding endeavor, as changing the size of a crystallizer drastically affects numerous important parameters governing the crystallization process. ... 

Zlota, A.A., Tools for Rapid Scale-up of Crystallization Processes, presented at the AIChE National Meeting, San Francisco, 2003. 

The exact scale-up of crystallizers is not possible because it would be necessary to preserve similar flow characteristics of both liquid and solid phases together with identical temperatures and supersaturations in all equivalent regions. The scale-up of simple agitated vessels containing a liquid phase alone has long been recognized as a difficult problem. The two dimensionless numbers most frequently encountered in the analysis of stirrers and agitators are the Reynolds number, Re, and the Froude number, Fr ... 

Stirring is typically the most critical parameter in scale-up of crystallization processes, namely, for batch crystallizations. Two aspects have to be considered ... 

Gahn, C. and Mersman, A., 1999b. Brittle fracture in crystallization processes Part B. Growth of fragments and scale-up of suspension crystallizers. Ibid. pp. 1283-1292. 

PloB, R., Tengler, T. and Mersmann, A., 1986. Scale-up of MSMPR-Crystallizers. German Chemical Engineering, 1, 42-48. 

Crystallization Process Systems brings together essential aspects of the concepts, information and techniques for the design, operation and scale up of particulate crystallization processes as integrated crystal formation and solid-liquid separation systems. The focus of the book, however, is on crystallization only dealing with related unit operations as far as is necessary. It is therefore... 

From the applications point of view, mutual diffusion is far more important than self-diffusion, because the transport of matter plays a major role in many physical and chemical processes, such as crystallization, distillation or extraction. Knowledge of mutual diffusion coefficients is hence valuable for modeling and scaling-up of these processes. 

Separations for removing undesirable by-products and impurities, and making suprapure fine chemicals constitute a major fraction of the production costs. There is an enormous variety of methods for product separation and purification and many books on the subject have been published. Here, we deal with the problem in a very general way and we refer the reader to advanced books for details. Conventional techniques for product isolation and purification, such as fractional distillation, extraction, and crystallization, still predominate. Some guidelines for scale-up of these techniques and producing experimental data for scale-up are given in Chapter 5. More information on specific separation and purification techniques applied to particular problems of fine chemicals manufacture the reader can find in Chapter 6. 

AM Collins, C Maslin, RJ Davies. Scale-up of a chiral resolution using cross-linked enzyme crystals. Org Process Res Dev 2 400-406, 1998. 

In scaling up a crystallizer for producing a crystal product of equivalent characteristics, the following must be kept constant ... 

Genck, W. J. (2000). The effects of mixing on scale-up—how crystallization and precipitation react. Chem. Process., 63,47. [256]... 

The first method of enantiomeric separation by direct crystallization is the mechanical technique use by Pasteur, where he separated the enan-tiomorphic crystals that were simultaneously formed while the residual mother liquor remained racemic. Enantiomer separation by this particular method can be extremely time consuming, and not possible to perform unless the crystals form with recognizable chiral features (such as well-defined hemihedral faces). Nevertheless, this procedure can be a useful means to obtain the first seed crystals required for a scale-up of a direct crystallization resolution process. When a particular system has been shown to be a conglomerate, and the crystals are not sufficiently distinct so as to be separated, polarimetry or circular dichroism spectroscopy can often be used to establish the chirality of the enantiomeric solids. 

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