Nucleation control, crystal growth

Where crystalline materials are involved, a supersaturated solution is set up prior to the onset of crystallization, followed by controlled crystal nucleation, controlled crystal growth and finally controlled cessation of growth. 

As discussed in section 2.4.4 the coordinating ability of a solvent will often affect the rate of nucleation and crystal growth differently between two polymorphs. This can be used as an effective means of process control and information on solvent effects can often be obtained from polymorph screening experiments. There are no theoretical methods available at the present time which accurately predict the effect of solvents on nucleation rates in the industrial environment. 

The dispersant property of the CPI is impeded by the nucleation enhancement performance of a pour point improver. In other words, the CPI functions to inhibit crystal growth while the pour point improver functions to maintain and control crystal growth. These two performance properties result in an antagonism between... 

Schwartz et al. evaluated the use of fibre-optic probe dispersive Raman and PLS calibration to study crystallisation in a hanging drop experiment. They could show that the lysosome concentration could be monitored during the experiment through the concentration phase, nucleation and crystal growth [27], In later experiments, they were able to utilise in-line Raman data to control the concentration of lysozyme to affect the crystallisation path and thereby obtaining the desired large single crystals [28], The same setup was used for crystallisation of apoprotein. Also in this case the Raman data were used to control the evaporation and thus the supersaturation for optimised crystal size [29]. 

McCauley J.W. and Roy R. (1974) Controlled nucleation and crystal growth of various CaCC>3 phases by the silica gel technique. Amer. Mineral. 59, 947-963. 

Wheeler A. P., George J. W., and Evans C. R. (1981) Control of calcium carbonate nucleation and crystal growth by soluble matrix of oyster shell. Science 212, 1397-1398. 

Meeting crystal product specifications with a robust, repeatable process requires careful control and balancing of nucleation and growth kinetics. Careful structuring of the environment can dictate the fundamental mechanisms of nucleation and crystal growth and their resultant kinetics. Undesired polymorphs can be often minimized or eliminated by suitable control of rate processes. 

A commonly used protocol used in controlling crystallization processes is to establish a seed bed prior to the bulk crystallization process. This significantly aids in the reproducibility of the crystallization. This is effected by determining the saturation point of the system and then adding authentic product prior to reaching this point. Once the seed bed is maintained, the system by default has been saturated with the desired product and by either addition of anti-solvent or with controlled cooling, both nucleation and crystal growth can be controlled. 

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