Introduction to Crystallization of Fine Chemicals and Pharmaceuticals - Molecules: Nucleation, Aggregation and Crystallization - page 169

is to add seed crystals which, through secondary nucleation, will generate
the desired number of crystals. In this case, the seed crystals have to be large
enough to spawn nuclei efficiently (Mullin, 1993). The number of seeds to
be added depends on nucleation kinetics and on the way the process is run.
Primary nucleation is undesirable. The third strategy is to render the pri-
mary nucleation more reproducible, by so-called induction seeding (Moore,
1994). Usually, in practice, it is recommended to add a proportion of seeds
corresponding to a few percent by mass of the production.
Analogously to cooling crystallization, “controlled conditions” can be
achieved by controlling the rate of evaporation (Larson, Garside, 1973) or
by controlling the feed rate in, for example, drowning-out crystallizations
(Tavare, Chivate, 1980). The supersaturation should be generated very
slowly to start with, and increase along with the available crystal surface
area. In drowning-out crystallization, there is a possibility that local feed
point conditions affect the product. It is also important to bear in mind that
in such processes the chemical composition of the solution changes grad-
ually during the process.
A reaction crystallization process is often significantly more compli-
cated. During a reaction crystallization, very high supersaturation levels can
frequently arise in the region where the reactants are mixed. In reaction
crystallization, either one reactant solution is added to a stirred solution of
the other reactant, or both solutions are added simultaneously. The effect of
process variables such as the type of stirrer, stirring rate, location of the feed
point, reactant concentrations, and the rate of addition, have been studied
for the former process type by Åslund and Rasmuson (1992). Benzoic acid
was crystallized by the addition of hydrochloric acid to a solution of sodium
benzoate. The results show that the average size of the crystals produced
increases with increasing agitation rate, passes through a maximum, and
then decreases. The produced crystals are larger if the feed point is located
close to the impeller instead of at the surface. At any given level of supplied
agitation energy, different impellers give the same product size. It has been
found that it is possible to show all the results of the effects of hydrody-
namic conditions on one single diagram, where the product size is plotted
against the feed point mixing energy dissipation rate. In addition, the results