Crystallisation Notes

7/25/2019 Crystallisation Notes

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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 ecient than distillation (heat of crystallization < heat of

vaporization)

highly selective purication technique only specic solute atom

(molecule) can t into site within growing lattice

No stirringin vessel

!) simple

") local#transient spatial supersaturation variations

$) non-uniform product

With stirringin vessel

!) smoothen out supersaturation proles

") more uniform products

$) smaller batch times

Ways to generate supersaturation

!) %ooling & lower ', lower solubility (by thermodynamics), (common case)

") olvent evaporation & remove solvent (use when solubility changes little

with ' change)

$) rowning out & add anti-solvent to reduce solubility

*) alting out & add common ion to alter solubility

+) %hemical reaction & use chemical reagents to alter solubility

) p ad.ustment & protein for e/ample, zwitterionic


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Supersolubility (or supersaturation)

'his condition must e/ist before crystallization can occur0

upersaturated solution (12'3456 or 534756 zone) & spontaneous crystallization is

probable but 28' inevitable

9or :6'3'3456 zone & spontaneous crystallization is not possible, but adding

seeds can induce nucleation and therefore induce crystallization

1nsaturated solution ('3456 zone) & no crystallization is possible0

Seeding is used to:

!) %ontrol %

") ;revent formation of thermodynamically unstable crystal forms

$) educe induction time

MSZW (Meta-Stable-Zone-Width)

6/tent of supersaturation before suciently high level of supersaturation causes

spontaneous formation of crystals0

:=> depends on

!) :i/ing

") 7mpurity level

$) aturation temperature

*) ate of supersaturation generation

+) 7mpurity level

What happens in the various supersaturation generation ethods?

!) %ooling only ' is lowered, no change in concentration of solute

") ?acuum ' is lowered (due to vacuum pressure), concentration of solute

increases

$) 6vaporation 'emperature is @ept constant, but solvent evaporation increase

solute concentration


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!olyorphs

iAerent crystal structures having diAerent physical properties but retain chemical

identity0

"soorphs

efers to two or more substances that crystallize in almost identical crystalline

forms0

Crystal habit

efers to e/ternal appearance of the crystal (shape of crystal of a crystal on a

macro scale)

'ype of crystal habit depends on

!) 'emperature

") olvent

$) upersaturation level

*) %ooling rate

+) 3gitation rate

) 7mpurity prole (stunts growth in certain directions)

Crystallization occurs in #W$ steps

!) Nucleation& phase separation step, BbirthC of new crystalsD need large driving

force (supersaturation than in growth step)D depends on

(a) local supersaturation values

(b) crystal concentration in suspension

(c) hydrodynamic interaction between crystals and solution

:i/ing must be turbulent to ensure good bul@ circulation (but avoid attrition)

and have good heat transfer characteristics

omogeneous nucleation & spontaneous nucleation

eterogeneous nucleation & addition of foreign particle (28' the same

crystal desired)

olute induced nucleation & addition of desired crystal seeds

epends on degree of mi/ing-agitation speed (2)-impeller shape ()-reactor geometry-feed addition

;rimarynucleatio

econdary


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

two steps

(3) %i&usion o' solute olecules to solid sur'ace

(4) "ntegration o' solute into lattice structure (sur'ace reaction)

E F d5#dt F KG/ d%g


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Controlling CS%

1)Control Nucleation rate by:

(a) 'emperature control

(b) ?ary anti-solvent rate, type of solvent

(c) ?ary degree of mi/ing

2)Control Growth rate by:

(a) elective removal of nes

(b) eed with particular size crystal (:8' 6996%'7?6)

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Crystallisation Notes