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1. Crystallization
* Definition :
Crystallization is the process of formation of solid crystals precipitating from a
solution, melt or rarely deposited directly from a gas . Crystallization is also a
chemical solid–liquid separation technique, in which mass transfer of a solute from
the liquid solution to a pure solid .
*Importance of crystallization :
1- purification of drugs .
2- improve bioavalability of the drug and choose the most stable form.
3- a crystalline powder is easily handled ,stable , possesses good flow properties and an
attractive appearance .
* Application of crystallization :
Crystallization is a key component of almost all processes in the manufacturing of
small molecule pharmaceuticals. it is essential in both processing and
pharmaceutical development.
Since the properties of a solid material (polymorphism) can dramatically affect the
process or the product’s compliance and effect (dissolution rate for
example), monitoring and controlling the isolation of solids for the various
applications through crystallization is of paramount interest.
so crystallization used in :
1- purification of drug
2- better processing characteristics
3- ease for handling
4- improved physical stability
5- sustained realese
6- improved bioavailability
7- preparation of organic and inorganic API
8- separation of API from galenical extracts
9- manufacturing of pure API by high yield

2. * Theory of crystallization :
The three major stages in the process of Crystallization are-
1. Super saturation of the solution : It can be done by three ways.
Heating the solution
Cooling the solution
Salting out
2.Nucleation : This takes place in several steps.
During their random motion, the atoms/ molecules/ ions will come closer to one
another and forms aggregates called as CLUSTERS.
These clusters will combine to form an EMBRYO. In this stage only the lattice
formation begins. This embryo’s combine to form NUCLEI.
From nuclei crystals are formed
3.Crystal Growth : Once the crystals are formed, nuclei formation stops and
crystal growth begins.

3. *Crystallization crystallizers :
Draft tube baffle technology:
This type of crystallization is especially designed for low
viscosity products when a narrow crystal size distribution
is expected.
Super saturated product enters into a chamber containing
the massecuite (mixture of solids and solution).
Instantaneously, the product crystallizes around the
crystals that are already inside the vessel so that the
solution reaches the saturation point. Inside the chamber, a
stirrer creates a high circulation flow in order to give a
good repartition of the crystals in the massecuite.
On the side of the vessel, baffles create a quiet zone where
an upward flow brings the smallest crystals out of the
vessels. They are re-melted and put back in the vessel.
Forced circulation crystallization:
The design of such a crystallization unit is very similar
to a forced circulation evaporator. A vertical tubular
heat exchanger is only preferred due to the high
viscosity of the massecuite.
This type of crystallization unit is designed for the
crystallization of salts out of effluent.