CrystallizationBy Keikhosro Karimi

- Crystallisation is used for the production, purification and recovery of solids.

h l f ll ll h l h- Enthalpies of crystallisation are generally much lower thanenthalpies of vaporisation, and crystallisation may be carried out closer to ambient temperature thereby reducing energy requirements.requirements.- Crystallization separates a material from a supersaturated solution by creating crystal nuclei and growing these nuclei to the desired size.

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Purification of bacteria membrane proteins by Crystallization

Multiple Homologues

DetergentgScreening

Crystallization

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In 1926 , James Sumner

Crystallized the first enzyme urease

and demonstrated that it is aand demonstrated that it is a

protein.

J. Sumner

• In the 1930s John Northrop pcrystallized pepsin, trypsin, and other digestive enzymes and foundother digestive enzymes and found them also to be proteins. J.H.Northrop

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Crystallization is a key component of

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Crystallization is a key component of almost all processes in the manufacturing of small molecule pharmaceuticals.

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When we use crystallization?

- This separation technique is applicable to those fermentation products that have a low solubility in the solvent utilized.

Th i i ll li h d l- The separation is usually accomplished at low temperatures so that there is the advantage of minimal product loss for thermally sensitive materials.

The solution’s supersaturation which precedes the actual- The solution s supersaturation, which precedes the actual crystallization, is usually accomplished by the removal ofsolvent or by lowering the solution temperature. The driving force for the formation and growth of crystals is related to theforce for the formation and growth of crystals is related to the extent of supersaturation.

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Solubility

We have observed that some chemicals dissolve in water, are soluble, and some do not, are insoluble. For chemicals that are soluble there is a limit to how much of the substance will dissolve. This limit isis a limit to how much of the substance will dissolve. This limit is known as solubility. Solubility is the maximum concentration for a solution with a given solute at a given temperature. Every substance has a unique solubility. Solubility can be expressed in any units of

t ti b t i l d i f l t 100concentration, but is commonly expressed in grams of solute per 100 ml of water. For example, at 25.0 0C, the solubility of sodium chloride is 35.0 grams per 100 ml of water. That means that you can dissolve up to 35.0 grams of sodium chloride in 100 ml of water. If you add p g ymore than 35.0 grams the solid will simply not dissolve and the system will reach a condition known as dynamic equilibrium. This condition occurs when the rate of dissolving becomes equal to the rate of crystallization Dissolving never stops it simply is nullified by

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rate of crystallization. Dissolving never stops, it simply is nullified by the reverse process, crystallization, occurring at the same rate.

I d f t l t l t d th l ti t b

Supersaturation

In order for crystals to nucleate and grow, the solution must be supersaturated; that is, the solute must be present in solution at a concentration above its solubility. Different methods may be used for creating a supersaturated solution from one which is g pinitially undersaturated. The possible methods depend on how the solubility varies with temperature.

Either evaporation of water or cooling may be used to crystallizeEither evaporation of water or cooling may be used to crystallize potassium nitrate (KNO3), while only evaporation would be effective for NaCl. An alternative is to add a solvent such as ethanol which greatly lowers the solubility of the salt, or to add a reactant which produces an insoluble product. This causes a rapid crystallization perhaps more properly known as precipitation.

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Supersaturation

A solution that is in thermodynamic equilibrium with the solid phase of its solute at a given temperature is a saturated solution, and a solution containing more dissolved solute than that given by the equilibrium saturation value is said to be supersaturated. The degree of supersaturation may be expressed by:The degree of supersaturation may be expressed by:

D = c − cwhere c and c are the solution concentration and the equilibrium saturation value, respectively.

The supersaturation ratio, S, and the relative supersaturation, are then: S = c/c

AndAnd= S − 1

Solution concentrations may be expressed as mass of anhydrate/mass of solvent or as mass of hydrate/mass of free solvent.

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Supersaturation is typically obtained by cooling or evaporation.

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Crystal formation from a solution

C li li b li h d i di tl ith

Crystal formation from a solution

- Cooling: cooling may be accomplished indirectly with build-in cooling surfaces if there is no possibility of incrustation formation.

Vacuum evaporation or cooling: When there is the- Vacuum evaporation or cooling: When there is the possibility of incrustation formation, vacuum cooling may be used. This approach has other requirements on the solution such as a minimum amount of dissolved gasessolution, such as a minimum amount of dissolved gases and a solution boiling temperature near that of the solvent. - Evaporation: Evaporation to reach supersaturationdiffers from vacuum cooling in the larger amount of solvent g gremoved by the evaporator and in the steady supply of heat to the evaporator. - Chemical Addition: Should either of these techniques

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prove inadequate, the crystalline product may be salted out by the addition of chemicals.

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Amount and particle size distribution

The amount and particle size distribution of crystalsproduced from a solution with a given crystallizer is afunction of:function of:

- Nucleation process

- Crystal growth process.

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Crystal formationCrystal formation

Crystal nucleation:Nucleation: the creation of crystalline bodies within a supersaturated fluid.fluid.It is a complex event, since nuclei may be generated by many different mechanisms.

N l ti l ifi ti hNucleation classification schemes:

-Primary nucleation: in the absence of crystals

- Secondary nucleation: in the presence of crystals.

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Primary nucleation

Classical theories of primary nucleation are based on sequences of bimolecular collisions and interactions in a supersaturated fluid. Such primary nucleation is known as homogeneous, althoughSuch primary nucleation is known as homogeneous, although the terms spontaneous and classical have also been used.

Secondary nucleationSecondary nucleation can, by definition, take place only if crystals of the species under consideration are already present. Since this is usually the case in industrial crystallisers, secondary nucleation has a profound influence on virtually all industrial crystallisationprocesses.

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Primary nucleationPrimary nucleation (both homogeneous and heterogeneous) has been modeled with the following

• B is the number of nuclei formed per unit volume per unit time. • N is the number of nuclei per unit volume. p• kn is a rate constant. • c is the instantaneous solute concentration. • c* is the solute concentration at saturation. • (c c*) is also known as supersaturation• (c–c ) is also known as supersaturation. • n is an empirical exponent that can be as large as 10, but generally ranges between 3 and 4.

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S d l tiSecondary nucleation

The following model, although somewhat simplified, is often used to model secondary nucleation:

• k1 is a rate constant. • MT is the suspension density. • j is an empirical exponent that can range up to 1.5, but is generally 1generally 1. • b is an empirical exponent that can range up to 5, but is generally 2.

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CRYSTALLIZATION FROM SOLUTIONS

-Cooling crystallizers

-Evaporating crystallizers

-Vacuum (adiabatic cooling) crystallizers

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Cooling crystallization

Whenever the conditions are favorable, crystal formation results from simply cooling the solution

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Cooling crystallizers

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Evaporating crystallizers

If the solubility of a solute in a solvent is not appreciably decreased by lowering the temperature, the appropriate degree of solution supersaturation can be achieved by evaporating some of the solvent and the oldest and simplestachieved by evaporating some of the solvent and the oldest and simplest technique, the use of solar energy, is still employed commercially throughout the world.

E i lli ll d d d dEvaporating crystallisers are usually operated under reduced pressure toaid solvent removal, minimise heat consumption, or decrease the operating temperature of the solution, and these are described as reduced-pressure evaporating crystallisers .evaporating crystallisers .

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Magma forced circulation crystallizer

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V ( di b ti li ) t lliVacuum (adiabatic cooling) crystallisers

A vacuum crystallizer operates on a slightly different principle from the reduced-pressure unit since supersaturation is achieved by simultaneous evaporation andpressure unit since supersaturation is achieved by simultaneous evaporation and adiabatic cooling of the feedstock. A hot, saturated solution is fed into an insulated vessel maintained under reduced pressure. If the feed liquor temperature is higher than the boiling point of the solution under the low pressure

i i i h l h li l di b i ll hi d hexisting in the vessel, the liquor cools adiabatically to this temperature and the sensible heat and any heat of crystallization liberated by the solution evaporate solvent and concentrate the solution.

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Continuous crystallisers

The majority of continuously operated crystallisers are of three basic types: forcedcirculation, fluidised-bed and draft-tube agitated units.

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Fluidized-bed crystallizers

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Draught-tube agitated vacuum crystallizers

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