Crystallization

Crystallization of
organic solids
Crystallization: a first order phase change in which
solid product is isolated from a solution, melt, vapor
or even from solid phase
Supersaturation: prerequisite for achieving
crystallization from solution

Solution
Crystallization
-crystallization of an
organic compound
dissolved in a solvent
or solvent mixture

Melt Crystallization
-Solution evaporation
leads to solvent
inclusion or co-crystal
formation (melt
cooling)

Crystallization from a
Solid Phase
-nucleation of a new
compound from a solid
phase

Hydrothermal and
Solvothermal Crystallization
-Crystallization in the
presence of a solvent at
temperatures higher than the
boiling point of solvent

Crystallization of Chiral
Solids
- Chiral: type
of molecule that has a
non-superposable mirror
image

Solubility Diagram
Crystallization-occurs ONLY in the
supersaturated region
Undersaturated-Below the
solubility
Metastable Zone Width (MSZW)is a critical parameter in the
crystallisation process as it reveals
the nucleation behaviour of the
system
MSZW- a nucleation kineticlimited parameter that is highly
dependent on process conditions

Nucleation
Initiation of a phase change in a
small region, such as the formation
of a solid crystal from a liquid
solution
Consequence of rapid local
fluctuations on a molecular scale in a
homogeneous phase that is in a
state of metastable equilibrium
This transformation requires
traversing a free energy barrier
Primary nucleation (homogeneous)spontaneous
Secondary nucleation
(heterogenous)-induced by the
presence of foreign particles

Crystal Growth
Crystal growth is a major stage of
a crystallization process, and consists
in the addition of new atoms, ions,
or polymer strings into the
characteristic arrangement of a
crystalline Bravais lattice
Once a crystal is stabilized from the
critical nucleus, the growth units can
diffuse from the surrounding
supersaturated solution to the
surface of the critical nucleus an
incorporate themselves onto the
crystal
Bravais lattice: is an infinite array of
discrete points generated by a set of
discrete
translation
operations
described by:

where ni are any integers and ai are

known as the primitive vectors which
lie in different directions and span
the lattice

Polymorphism
Polymorph: Crystals in which chemical compound
takes different arrangements of molecules-solid
state phenomenon
Different morphologis, solubilities, color, melting,
sublimation temperatures, densities, thermal/
elctrical conductivities
Pharmaceutical industry-affect processing
properties such as filtering, drying, flow,
tabletting, rate of dissolution, shelf life and
bioavailability

Thermodynamics of Polymorphism
Monotropic forms- A is
more stable that the other
at all temperatures
Enantiotropic forms-there
is a transition temperature
below melting point
Transition temp:
temperature at which the
free energy of polymorph
A intersects the free
energy of polymorph B

Intermolecular interactions
A molecular crystal- periodic
assembly of molecules
Van der Waals Interactions: total
of attractive and repulsive forces
between molecules, inclusive of
hydrogen bonds.
Hydrogen Bonds: stabilizing
interaction between donor X..H
and acceptor Y..Z
Halogen Bonds
Other interactions: polarization

Crystal Engineering
Understanding of
intermolecular
interactions - context
of crystal packingutilization of such
understanding designing of new
solids with desired
physical and chemical
properties