Ahsun Ali, Waqas

Ahmed,Usman
Ghafoor, Usman Ali
Khan.

CRYSTALLIZATION
Defining the term crystallization and explaining the mechanism of how
crystals are formed from a supersaturated solution. Also, providing real-life
applications of this unit operation.

Contents
Introduction:..................................................................................................................................2
Mechanism of Crystallization:......................................................................................................2
Nucleation:..................................................................................................................................2
1.

Homogenous Nucleation:............................................................................................3

2.

Heterogeneous Nucleation:.........................................................................................4

Crystal Growth:.........................................................................................................................4
Crystallization at Industrial scale:...............................................................................................4
Understanding the Polymorphism:..........................................................................................5
Process Design:...........................................................................................................................5
Process Optimization:................................................................................................................5
Scaling up & Mass Production:................................................................................................5
Types of Crystallizers:...................................................................................................................5
1.

Forced Circulation crystallizers:.......................................................................................5

2.

Draft-tube Crystallizer:......................................................................................................6

3.

Surface cooled Crystallizer:...............................................................................................6

Other types of crystallizers:..........................................................................................................7

Applications of crystallization process:.......................................................................................7

Introduction:
Crystallization is a separation technique. It is used to improve the purity of a substance dissolved
in a solvent. To define, crystallization refers to the separation of a dissolved substance, in solid
form, from its supersaturated solution. It is a unit operationno chemical reaction takes place
during this process.
The solution of substance to be separated is heated in an open container so as to evaporate the
solvent. Until, the solution becomes saturated i.e. the solvent is holding the maximum amount of
solute it can at that temperature. Afterwards, the solution is allowed to cool until crystals begin to
form. This is because at lower temperature, the solubility of the solute decreases and the
undissolved solute separates into, relatively pure, solid particles. This separation occurs until, the
solution again becomes saturated at the lowered temperature.

Mechanism of Crystallization:
The crystallization process is an extremely complex phenomena. No clear ruling exists to
properly explain this technique. However, there are many theories that explain the steps involved
in crystallization. Following are the two main steps of crystallization explained in light of
thermodynamics.

Nucleation:
Nucleation is the starting point of crystallization process. In this step, a group of ions, atoms,
molecules form a
small group in a
particular
arrangement. On
this site, more and
more atoms, ions
or molecules settle
and the crystal is
said to grow.
Nucleation step is
a metastable form
i.e. a locally
stable form but not
an absolute stable
form.
This
condition
exists
for a very small
interval of time
and under very
stringent physical conditions. Classical thermodynamics explains this step in a very intuitive
way. According to thermodynamic principles, the existence of a single or multiple phase of a
system depends on the relative free energy of that phase. A system sustains or shifts from a phase
depending on whether that current phase has a lower or higher Gibbs free energy than the new
phase. The Gibbs free energy is given by
G = H TS

Where,
H = Enthalpy of the substance
T = Temperature of the substance
S = Entropy of the substance
Since the absolute enthalpy and entropy of a substance cant be measured, consequently, the
Gibbs free energy is measured as a difference from some reference state where G, H and S are
taken to be zero. Alternatively,
G = H - TS
After some algebraic manipulations, a more practical form of this expression is obtained
dG = Vdp SdT
If pressure is kept constant then,
(G/T)p = -S
This expression shows that as the temperature is increased, the Gibbs free energy decreases. The
net energy and hence
the
most
stable
physical state is a
compromise between
the lowest enthalpy of
the substance at a
particular temperature
and
the
highest
entropy.
As the temperature
increases, the net free
energy decreases. As a
result, the free energy
for the solid phase
becomes higher than
the free energy for the
liquid phase and the
substance shifts from
solid to liquid at the melting point. Same is the case for liquid and vapor phases.
In crystallization, the reverse occurs i.e. ions, radicals dissolved in a liquid combine to form the
more arranged and compact solid crystals. Again, the changes in free energy dictate the
formation of solid phase.
Nucleation is of two types:
1. Homogenous Nucleation:
In this type of nucleation, ions present in the solution interact with each other to form the
nucleus. This nucleus then provides the site for growth of the crystal. This type of nucleation is

seldom achieved and is observed when the concentration of the solute is very high in the
solution.
2. Heterogeneous Nucleation:
In this type of nucleation, some other surface acts as the center on which ions or atoms arrange in
a proper arrangement. It can be a dust particle, the surface of the container etc. This is the more
common type of nucleation that occurs in real-life crystallization process because no solution can
be made absolutely pure.

Crystal Growth:
This is the second major step in the crystallization process. In order to achieve required crystal
shape and size, it is imperative that crystal growth is controlled and uncontrolled nucleation is
prevented as shown in the first figure. This is done by first understanding the enantiotropy i.e.
the change in ranking of stability of various polymorphs by changing temperature. This becomes
very important if enantiotropy zone exists between the evaporation temperature of the solvent
and the cooled temperature at which crystals form. On the basis of this information, the
appropriate solvent is chosen and the Meta stable zone width (MSZW) is found. The MSZW
provides the favorable temperature and concentration zone in which controlled crystal growth
can be achieved.
Normally, crystals are grown by establishing a temperature gradient between the hot solution and
relatively cool seed crystal. As aforementioned, normally heterogeneous nucleation is more
dominant, a foreign particle (it can be a crystal of the solute) is introduced. Due to the
temperature difference, fluid region close to the seed crystal is cooled and by the thermodynamic
principles more crystals are formed. Some of the factors that are to be considered during crystal
growth are:
1. Random nucleation and uncontrolled crystal growth is to be avoided. First figure shows
the conditions under which, if a seed crystal is added, runaway crystallization will
occur.
2. The geometry of the crystals formed stringently depends on the temperature gradient
between the seed crystal and the hot solution.
3. The temperature gradient needs to optimized i.e. it must be high enough that suitable rate
of crystallization is achieved but not too high because very high temperature gradients
result in sub-grain boundary formation in crystals or disorientation of crystals.

Crystallization at Industrial scale:

Understandi
ng the
polymorphi
sm

Process
Design

Process
Optimizatio
n

Scaling Up
& Mass
Production

Understanding the Polymorphism:

As previously mentioned, the preliminary step to proper crystallization is to understand the
kinetics and traits of the substance which is to be crystallized. Thermodynamic laws and the
chemistry of the substance provide a sound cognizance of the process. Sometimes, especially in
pharmaceutical industry, it is very crucial to obtain a specific crystal structure otherwise the
potency or the physical characteristics may completely be altered. Studying and understanding
the enantiotropy in this case becomes important.

Process Design:
After understanding the dynamics of the crystallization process at hand, the suitable solvent and
operating conditions i.e. concentration and temperature are selected. The choice of solvent
depends on the MSZW of each solvent. Solvent with the more MSZW provides a more robust
crystallization process.

Process Optimization:
In this step, the critical factors that can banefully affect the process are determined e.g.
agglomeration, polymorphic conversion etc. Cooling profile, purity, stirring (type and speed),
space volume yield and filterability are some of the factors that are optimized in this step.

Scaling up & Mass Production:

After the process is completely optimized for the required crystallization process, the equipment,
feed rate and product rates are scaled up according to requirement.

Types of Crystallizers:
1. Forced
Circulation
crystallizers:
Some of the characteristics of this
crystallizer are:

It uses adiabatic evaporative

cooling to create the supersaturated
solution.
Employs magma recirculation to
control super saturation generation.
It can, in some cases, provide a
mechanism for classified product
removal.

Forced circulation crystallizer consists of a

closed, conical bottom vessel. It comprises
of a recirculation process which consists
of a recirculation piping system and a
pump. The recirculating magma is fed,
tangentially, to the vessel and fresh feed is
added to the recirculation piping ahead of
the recirculation pump. The product slurry
is withdrawn from the system after the crystallizer outlet and feed inlet.

2. Draft-tube Crystallizer:
Draft-tube crystallizers have two variants:
baffled and unbaffled. Normally, baffled
draft-tube crystallizers are used since they
provide a mechanism for fine particles
dissolution. A baffled draft-tube (DTB)
consists of a vessel containing an internal
skirt baffle which is installed so as to
provide a partitioned settling zone.
Internally, the baffle has a draft-tube that is
centered by support vanes. An agitator is
attached to the bottom of the draft tube.
Some of the characteristics of the drafttube crystallizer are:

It uses direct-contact cooling,

evaporation
or
adiabatic
evaporative cooling to generate
super saturation.
Provides
a
mechanism
for
classified product removal.
Employs
internal
magma
recirculation to control super saturation.

3. Surface cooled Crystallizer:

A conventional baffled surface cooled crystallizer consists of a shell and tube heat exchanger, a
vessel containing a skirt baffle and
a recirculation pump. The baffle
acts as a separation media between
the active crystallization volume
and the settling zone. Feed inlet is
located on the recirculation pipe
just before the recirculation pump.
Settling zone outside the baffle
provides the outlet for the mother
liquor. A central tube extending
into the active crystallization
volume recirculates the magma
through the crystallizer vessel.
Some of the characteristics of the
surface cooled crystallizer are:

Uses only surface cooling

to
generate
super
saturation.
Does not provide a mechanism for classified product removal.
Can be used for fines dissolution only if a baffle is installed.

Other types of crystallizers:

Fluidized bed crystallizer

Magma type crystallizer
Induced circulation crystallizer
Direct contact refrigeration crystallizer

Applications of crystallization process:

Pharmaceutical industry
Food (especially sugar) industry
Chemical industry
Fertilizers industry
Cosmetics