Crystallisation notes

Crystallisation: particle formation process by which solute molecules in

solution form become solid phase with regular lattice structure
Precipitation: particles formed by decreasing solute solubility (by cooling,
evaporation, anti-solvent addition, chemical reaction, drowning out, salting
out)
Why crystallization (advantages)?
more energy efficient than distillation (heat of crystallization < heat of
vaporization)
highly selective purification technique only specific solute atom
(molecule) can fit into site within growing lattice
No stirring in vessel:
1) simple
2) local/transient spatial supersaturation variations
3) non-uniform product
With stirring in vessel:
1) smoothen out supersaturation profiles
2) more uniform products
3) smaller batch times
Ways to generate supersaturation
1) Cooling lower T, lower solubility (by thermodynamics), (common case)
2) Solvent evaporation remove solvent (use when solubility changes little
with T change)
3) Drowning out add anti-solvent to reduce solubility
4) Salting out add common ion to alter solubility
5) Chemical reaction use chemical reagents to alter solubility
6) pH adjustment protein for example, zwitterionic

Supersolubility (or supersaturation)

This condition must exist before crystallization can occur.
Supersaturated solution (UNSTABLE or LABILE zone) spontaneous crystallization is
probable but NOT inevitable
For METASTABLE zone spontaneous crystallization is not possible, but adding
seeds can induce nucleation and therefore induce crystallization
Unsaturated solution (STABLE zone) no crystallization is possible.
Seeding is used to:
1) Control CSD
2) Prevent formation of thermodynamically unstable crystal forms
3) Reduce induction time
MSZW (Meta-Stable-Zone-Width)
Extent of supersaturation before sufficiently high level of supersaturation causes
spontaneous formation of crystals.
MSZW depends on:
1) Mixing
2) Impurity level
3) Saturation temperature
4) Rate of supersaturation generation
5) Impurity level
What happens in the various supersaturation generation methods?
1) Cooling only T is lowered, no change in concentration of solute
2) Vacuum T is lowered (due to vacuum pressure), concentration of solute
increases
3) Evaporation Temperature is kept constant, but solvent evaporation increase
solute concentration

Polymorphs
Different crystal structures having different physical properties but retain chemical
identity.
Isomorphs
Refers to two or more substances that crystallize in almost identical crystalline
forms.
Crystal habit
Refers to external appearance of the crystal (shape of crystal of a crystal on a
macro scale)
Type of crystal habit depends on:
1) Temperature
2) Solvent
3) Supersaturation level
4) Cooling rate
5) Agitation rate
6) Impurity profile (stunts growth in certain directions)
Crystallization occurs in TWO steps
1) Nucleation phase separation step, birth of new crystals; need large driving
force (supersaturation than in growth step); depends on:
Depends on degree of mixing
(a) local supersaturation values
-agitation speed (N)
-impeller shape (D)
(b) crystal concentration in suspension
-reactor geometry
-feed addition
(c) hydrodynamic interaction between crystals and solution
Mixing must be turbulent to ensure good bulk circulation (but avoid attrition)
and have good heat transfer characteristics
Homogeneous nucleation spontaneous nucleation
Heterogeneous nucleation addition of foreign particle (NOT the same
crystal desired)
Seconda
ry
Solute induced nucleation addition of desired crystal
seeds
nucleatio

Primary
nucleatio

2) Crystal growth growth of crystals to larger sizes occurs in (assumed to be)

two steps:
(A) Diffusion of solute molecules to solid surface
(B) Integration of solute into lattice structure (surface reaction)
G = dL/dt = KG x dCg

Controlling CSD
1)Control Nucleation rate by:
(a) Temperature control
(b) Vary anti-solvent rate, type of solvent
(c) Vary degree of mixing
2)Control Growth rate by:
(a) Selective removal of fines
(b) Seed with particular size crystal (MOST EFFECTIVE)