Crystallization is a widely used separation and purification method involving two stages: formation of nuclei and crystal growth. It relies on a compound's limited solubility in a solvent, allowing crystals to form when conditions change to lower the solubility. Crystals form highly ordered structures that prohibit impurities, yielding a pure solid product. Common crystallization types include evaporative, cooling from solution/melt, and reactive precipitation. Crystallization is used in industries like pharmaceuticals, food, chemicals, and more to purify compounds and obtain high purity products.

1. CRYSTALLIZATION IN FINAL
STAGES OF PURIFICATION
Presented by Breena

2. CRYSTALLIZATION
 Crystallization is a separation and purification method
widely used for final purification of components
 The principle of crystallization is based on the limited
solubility of a compound in a solvent at a certain
temperature, pressure, etc. A change of these conditions
to a state where the solubility is lower will lead to the
formation of a crystalline solid
 Crystallization consists of two stages:
• formation of nuclei
• growth of crystals

3. CRYSTAL
 A crystal is a solid in which the constituent atoms,
molecules, or ions are packed in a regularly ordered,
repeating pattern extending in all three spatial
dimension
 The formation of such a highly ordered structure
prohibits foreign molecules from being incorporated into
the lattice, a solid product of high purity is obtained

4. SHAPES OF CRYSTALS

5. EXAMPLES
Crystal Angle of axes Length of axes Examples
Cubic (regular) α = β = γ = 90º x =y =z NaCl
Tetragonal α = β = γ = 90º x =y ≠z NiSO4
Orthorhombic α = β = γ = 90º x ≠y ≠z KMNO4
Monoclinic α = β = γ ≠ 90º x ≠y ≠z Sucrose
Triclinic
(asymmetric)
α ≠β ≠ γ ≠ 90º x ≠y ≠z CuSO4
Trigonal
(rhombohedral)
α = β = γ ≠90º x =y =z NaNO3
Hexagonal Z at 90º to base - AgNO3

6. TYPES OF
CRYSTALLIZATION
Crystallization processes can be distinguished by the
manner in which the supersaturation is created. The
most frequently applied types of crystallization are
 Evaporative crystallization
 Cooling crystallization from solution or the melt
 Reactive crystallization or precipitation
The choice for a certain method depends on the
properties of the compound to be crystallized, the feed
and the thermodynamics of the system

7. Continue…
 For compounds with a low solubility the standard option
is reactive crystallization or precipitation
 For compounds with a solubility higher than 200 g/kg, a
choice has to be made between evaporative and cooling
crystallization
 Evaporative crystallization is typically the preferred
option when the solubility is hardly dependent on T,
which implies that cooling the saturated solution will not
result in a significant amount of crystals

8. EVAPORATIVE CRYSTALLIZATION
 In evaporative crystallization, the crystallization is
resulting from the evaporation of the solvent. So, this
process creates a vapor and a suspension of crystals in
mother liquor
 The mother liquor contain the equilibrium concentration
of product
 The residual amount of product can be harvested by
recycling the mother liquor to the feed
 The high concentration of impurities can influence the
crystallization or the product purity

9. COOLING CRYSTALLIZATION
 Cooling crystallization is attractive when the solubility of
the product increases significantly with increasing
temperature
 the feed is cooled in a heat exchanger, which can be
situated inside the crystallizer or an external loop
 Crystallization can take place when the liquid is cooled
to a temperature below the equilibrium solubility

10. Melt Crystallization
 Melt crystallization can be regarded as a special form of
cooling crystallization process
 The main difference with cooling crystallization from
solution is the absence of solvents, which implies that
most melt crystallization processes are operated close
to the melting point of the pure product. The feed for a
melt crystallization process is an impure melt

11. PRECIPITATION
 In precipitation the supersaturation is created by the
mixing of two streams. The most common forms of
precipitation are
 Reactive crystallization is the process in which the
solid phase is formed due to a reaction between
components that were originally present in the two feed
streams
 pH shift crystallization often makes use of the change
in the chemical state/charge of ionic species with pH
Well known examples of ions that change state with pH
are for instance carbonate and phosphate

12. Continue…
 Anti-solvent (or extractive) crystallization The anti-
solvent is typically well-mixable with the solvent, the
crystallizing product has a lower solubility in the anti-
solvent and for economic and environmental reasons it
should be possible to recover the anti-solvent

13. FRACTIONAL CRYSTALLIZATION
 Fractional crystallization is a term that is used to
describe a process where repeated crystallization steps
are used to increase the purity of the product and/or to
increase the yield of the process
 Applications can be found in metal (metal refining), oil &
gas (e.g. oil dewaxing), food (e.g. palm oil fractionation)
 This second crystallization stage will operate at a higher
temperature than the first stage due to the higher purity
of the feed in the second stage

14. MECHANISM
 Crystallization consists of two stages:
• formation of nuclei
• growth of crystals
 For crystallization to happen the solution should be first
supersaturated thus the solution must contain more
dissolved material than it would under normal conditions
 Several methods can be used to obtain supersaturation
such as solvent evaporation, cooling, chemical reaction
and addition of a second solvent to reduce the solubility
of the solute, solvent layering and sublimation along with
other methods

15. FORMTION OF NUCLEI

16. Continue…
 The first step of crystallization is formation of nucleation
where crystals are formed when particles gather into
clusters. The clusters become stable nuclei after
achieving the critical cluster size. There are two different
nucleation formations – primary and secondary
 Primary nucleation is
 spontaneous and homogeneous in the absence of
foreign particles
 Heterogeneous in the presence of foreign particles then
the formation is induced by foreign particles and occurs
lower supersaturation concentration compared to
homogeneous primary nucleation

17. Continue…
 Secondary nucleation appears when crystals already
exist in the solution and it is caused by collision of
crystals. This type of nucleation formation is typical
mechanism in industrial crystallization because of low
supersaturation concentration

18. CRYSTAL GROWTH
 Nucleus size increases after the critical cluster size is
achieved
 Crystal growth increases its own dimension in thin
layers
 Crystal growth rate is affected by various physical
factors, such as surface tension of solution, pressure,
temperature and other factors

19. EXAMPLE
 Crystallization is typical downstream processing method
for high quality products with high purity requirements
 is widely used in organic acid production
 One of the most common organic acids is citric acid
which is used in several industries such as
pharmaceutical, food and beverage industries

20. Preparation of citric acid crystals
 After fermentation the broth is filtered and precipitated
with Ca(OH)2 at pH of 7.2 and temperature of 70-90 °C
 Calcium citrate crystals are formed in the reaction
 After filtration the calcium citrate is reacted with sulfuric
acid to precipitate the calcium in the form of calcium
sulfate
 Anhydrous citric acid is released (when reaction occurs
above 40 °C) and then clarified with active carbon and
crystallized with evaporation
 The resulted product has very high purity level due to
crystallization and therefore is suitable for foodstuffs or
pharmaceuticals.

21. Preparation of Citric acid crystals

22. Purification of benzoic acid by
crystallization

23. Advantages & Disadvantages
 has an advantage compared to other solid liquid
separation operations such as distillation since
crystallization is a rather energy efficient unit operation
and the yielded product has very high purity level and
therefore wide scale of end use opportunities
 Its main disadvantage is that it is a slow process and
crystals can degrade by the gain in moisture or loss of
solvent

24. APPLICATIONS
 the desalination of seawater
 the freeze-concentration of fruit juices
 the recovery of valuable materials such as metal salts
from electroplating processes
 the production of materials for the electronic industries
and in biotechnological operations such as the
processing of proteins
 low-temperature crystallization can be used as
purification method for liquid hydrocarbon mixtures in
petroleum industry
 For production of interferons, lysozymes and antibiotics

25. Continue…

26. THANK YOU FOR YOUR
ATTENTION