Introduction to Crystallization of Fine Chemicals and Pharmaceuticals - Molecules: Nucleation, Aggregation and Crystallization - page 160

and multifunctional types (van Rosmalen et al ., 1989). By identifying the
molecular structure of the crystal, it is possible, at least in principle, to
design additives having a specific function. The effects of tailor-made
additives depend on two properties: structural similarity and specific dif-
ference. The dosage of additive that is required is quite large: about 5 wt-%
if a change in shape is desired, and 10 wt-% for growth inhibition.
Tailor-made additives are suitable for organic substances, which have
complicated structures. Often by-products from previous reaction steps
can act as tailor-made additives. Ionic compounds often have relatively
simple and unspecific structures, and for such compounds, multifunc-
tional additives, such as phosphonic acids, polycarboxylic acids polysul-
phonic acids and polymers with different acid groups, are used. This type
of additive is generally active at concentrations in the range 10-50 ppm.
Some metal ions are known for causing strong effects in crystallization
processes.
Product purity
For many substances, a high purity is desired. Impurities can occur in the
product in at least four different ways (de Jong, 1984): (i) process solution
can adhere to the outer surfaces of the crystal, (ii) impurity molecules can
be incorporated into the crystal lattice, (iii) solution can be encapsulated
in cavities inside the crystal (inclusions), and (iv) impurities can be
adsorbed into lattice channels and cavities (Fig. 7). In addition, solution
can be encapsulated in agglomerate formations (occlusions). Depending
on the way in which impurities are present in the product, different kinds
of remedies are called for.
Incorporation of impurity molecules in the crystal lattice is caused by
similarities between substance and impurity, and is the most difficult kind
to remedy. Possibly, a reduction in growth rate can be beneficial. In a crys-
tallizer, the occurrences of inclusions in crystals are frequently the result
of too high a growth rate, or alternating growth and dissolution. One
example is repeated growth and dissolution in a heat exchanger, e.g. in an
oversized evaporation crystallizer. Inclusions are often the result when