Batch crystallization optimization studies

Using piecewise constant control profiles and orthogonal collocation on finite elements, this approach was further developed by Renfro (Renfro, 1986 Renfro et al, 1987) to deal with much larger problems. More recent simultaneous applications that involve SQP, orthogonal collocation, and piecewise constant control profiles have been presented by Patwardhan et al (1988) for online control, and by Eaton and Rawlings (1988) for optimization of batch crystallizers. These studies have shown that simultaneous approaches can be applied successfully to small-scale applications with complex constraints. 

Batch Crystallization Chapter 10 is devoted to batch crystallization where a phase diagram is used to find the supersaturation at which point material crystallizes. This is again one of the most studied batch operations. Similar to batch distillation, various modeling techniques are used to describe the operation of batch crystallizer, and optimization and optimal control problems are well studied. 

Determination of the optimal temperature (or supersaturation) trajectory for a seeded batch crystallizer is a well studied problem. This is a dynamic optimization or optimal control problem. The process performance is determined by the crystal size distribution and product yield at the final time. For uniformity of shape and size in the crystals in a seeded batch crystallization process, it is essential to ensure that the nucleation phenomena occurs to the minimum and mostly the seeded crystals grow to the desired size at a certain rate. If nucleation occurs in the initial phase, then there is a possibility that the nucleated crystal will compete with the seeded ones, thus if the phenomena is of late growth, then nucleation in the earlier phase is preferred. Thus, depending upon the process operation, many types of objective functions have been proposed [4]. 

In the prenomination phase, the polymorphism screen will be limited due to the amount of compound available, and strategies must therefore be employed to reflect this situation. Initially, the Medicinal Chemistry batches should be analyzed to gain preliminary evidence for the propensity of the compound to show variations in the solid-state form of the compound. It is possible that the Process Research and Development department will also be working on the synthesis and crystallization of the compound. Therefore, a useful starting place for searching for polymorphs is to screen the material produced by the process chemists as they attempt to optimize the crystallization conditions. Work can also be undertaken by the Pharmaceutical and Analytical departments, in parallel, to use some of the above methods to generate polymorphs. However, these initial studies will probably have to be carried out on a micro- or semi-microscale. 

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