Introduction to Crystallization of Fine Chemicals and Pharmaceuticals - Molecules: Nucleation, Aggregation and Crystallization - page 165

with each other for the chemical reaction to occur. Secondly, the crystals
are often relatively small, and suspension is not necessarily a major prob-
lem. Finally, the result is governed less by secondary nucleation than by
primary nucleation. It is common in these discussions to distinguish the
mixing action into macro - and micro-mixing , and sometimes also into
meso-mixing . Macro-mixing comprises large-scale mixing, whereby the
reactant streams are split into smaller liquid fractions, which are distrib-
uted in the vessel. Meso-mixing denotes mixing at the same approximate
level as the dimensions of the feed pipe, and is of particular relevance
when the process involves feeding of reactants. Micro-mixing comprises
the small-scale turbulence, shearing and straining of fluid layers and the
molecular diffusion that eventually brings the reactants together (Baldyga,
Bourne, 1986). The greater the proportion of the supplied energy that is
used to create turbulence, the better the micro-mixing becomes.
Control of the product crystal mean size
As shown earlier, the product size is governed by the number of crystals
that shares the total crystal mass. The crystals in a size distribution are
created by nucleation and possibly by fragmentation, or are added in the
form of seeds, and grow in size in the crystal growth process. The nucle-
ation rate is primarily decided by two factors. Both primary and second-
ary nucleation depend strongly on the supersaturation. Secondary
nucleation also depends strongly on the hydrodynamic conditions. Both
the nucleation rate and the crystal growth rate increase with the supersat-
uration, but the nucleation rate generally increases faster. Supersaturation
is generated through cooling, for example, and is consumed through crys-
tal growth by an increasing number of particles. Whether the total mass is
divided between a small number of large particles or a large number of
small particles is decided by the interplay, or competition, between nucle-
ation and crystal growth.
The supersaturation balance is a mass balance with a saturated solu-
tion as reference, and it describes how the driving force for crystallization
varies with the process conditions. The supersaturation in a batch process