1. E Mail ID : shwet.zawar@gmail.com
CRYSTALLIZATION
Presented By:
Mr. L R Zawar
HRPIPER, Shirpur.
E Mail ID :

2. Introduction
Spontaneous arrangement of the particles into a repetitive orderly array i.e., regular geometric pattern.
The liquids can solidify into crystalline forms, whenever attraction forces between particles are strong enough to overcome the disorderliness.
Crystallization differs from precipitation in that the product is deposited from a supersaturated solution.

3. Application of Crystallization
Purification of drugs
Better processing characteristics
Ease of handling
Better chemical stability
Improved Physical stability
Improved bioavailability
Sustained release
Miscellaneous

4. Characteristics of Crystals
Crystal Lattice : Orderly internal arrangement of particles in three-dimensional space.
Space Lattice: Three dimensional arrangement of particles in a crystal.
Unit cell: The smallest geometric portion, which repeats to build up the whole crystal.
Faces: A crystal is bounded by plane surfaces.
Axial angle: In the crystal, the angle between the two perpendiculars to the intersecting faces.
Axial length: the distance between the centers of two atoms.

5. Characteristics of Crystals
Crystal System or Forms:
A finite number of symmetrical arrangements are possible for a crystal lattice & these may be termed as crystal system or forms.
Depending upon the axial length & axial angle, crystal forms are designated as cubic, hexagonal, tetragonal, orthorhombic, monoclinic & triclinic.
A chemical substance may exist in more than one form i.e., polymorphism.

6. Characteristics of Crystals
Crystal Habits:
Crystal is a polyhedral solid with number of planer surfaces.
The shape & size of the crystals formed are markedly dependent on the conditions under which crystallization is carried out.
Depending on the arrangement of faces, crystal habits are described in different ways.
Columnar (Prismatic): Rod like particles having width & thickness exceeding that of needle type particles.
Blade: Long, thin & flat particles, which can also be referred to as being lath shaped.
Plate (lamellar or micaceous): Flat particles of similar length & width.
Tabular: Flat particles of similar length & width but possessing greater thickness & flakes.
Equant: Particles of similar length, width & thickness.
Acicular: Needle like prisms.

7. Pharmaceutical Solids
Amorphous
Crystalline
Polymorphs
Hydrates
Solvates
Isomorphs
Stable
Metastable

8. Theory of Crystallization
Mechanism of crystallization:
Supersaturation
Nucleus Formation
Crystal growth

9. Theory of Crystallization Supersaturation
Solution
Saturated Solution
Supersaturated Solution
Solvent > Solute
Solvent = Solute
Solvent < Solute
Supersaturation may be achieved through:
Evaporation of solvent from the solution
Cooling of the solution, if the solute has a positive heat of solution.
Formation of a new solute as a result of chemical reaction.
Addition of a substance, which is more soluble in solvent than the solid to be crystallized.

10. Theory of Crystallization Nucleation
Birth of very small bodies of a new phase within a homogenous supersaturated liquid phase.
Is a consequence of rapid local fluctuations at the molecular level when molecules or ions or atoms are in random motion in any small volume.
The initially formed crystals of molecular size, termed as nuclei.

11. Theory of Crystallization Nucleation
Methods of nucleation:
Soft or weak crystals on impact with moving parts in a crystallizer can break into fragments which act as nuclei.
Small crystals which are formed in the previous process are added to act as nuclei
In a supersaturated solution or under poor mixing, the needle like structures are observed on the ends of crystals. These structures grow faster.

12. Theory of Crystallization Crystal growth
Crystal growth is a diffusion process & surface phenomenon.
Accepted by surface
Solutes from Solution
Diffusion
Faces of crystals
Crystal Lattice

13. Mier’s Supersaturation Theory
Definite relationship between concentration & temp at which crystals will spontaneously form in an initially unseeded solution.
Supersolubility curve represents the limit at which nucleus formation begins spontaneously & point at which crystallization starts.

14. Mier’s Supersaturation Theory
Curve AB – Normal solubility (any point on the curve represents the solute in equilibrium with the solvent)
Curve FG – Supersolubility (nucleus formation begins spontaneously)
Stable zone – well defined zone below the solubility curve, unsaturation prevails, crystallization is not possible
Metastable zone – region between curves AB & FG. Spontaneous nucleation occurs.
Labile or unstable zone – Conditions of high relative supersaturation where only nucleation is favoured.
Crystallization expected to start at point P.
But according to Mier’s Theory, Crystallization starts nearer to point D.
Under ideal conditions of crystallization, nucleus formation starts at FG & crystal growth begins.
Concentration of substance roughly follows the curve DE

15. Conditions for obeying Mier’s Theory
The solute & the solvent must be pure.
The solution must be free from solid solute particles.
The solution must be free from foreign solid matter.
The solution must be protected from entry of any particle.
Soft or weak crystals must not form during the process.
There should not be any fluctuations in maintaining the temp

16. Limitations of Mier’s Theory
Crystallization starts at supersolubility curve, but crystallization takes place in an area rather than a line.
If the solution kept for longer periods, nucleation starts well below the supersolubility curve.
If the solution is available in large volume, nucleation starts well below the supersolubility curve (due to collisions of molecules)
Applicable when pure solute & pure solvent are used.
During storage dust particles can enter that may initiate nucleation.

17. Solubility Curves
Are useful for predicting the experimental conditions desired for crystallizing a substance.
Since supersaturation is achieved by reducing the temp, the influence of temp on solubility of a substance is important
Temp on x-axis & Solubility on y-axis
Curve 1: solubility increases with increase in temp. eg. Potassium nitrate.
Curve 2: solubility increases with increase in temp, but to a marginal extent. eg. Sodium Chloride.
Curve 3: solubility increases rapidly with temp, but inflections are observed in the curve to represent different hydrates. e.g. Sodium thiosulphate.
Curve 4: Unusual curve. Solubility increases with temp if it is in hydrated form. In monohydrate form, its solubility deceases. eg. Sodium carbonate.

18. Crystallizers
(Classified by the methods by which supersaturation is brought)
Supersaturation
by cooling alone
Supersaturation by
adiabatic cooling
Supersaturation
by evaporation
Salting
Evaporators
Batch
processes
Continuous
processes
Vacuum
Crystallizers
Krystal
Evaporators
Tank
Crystallizers
Swenson
Walker
Crystallizers
Without
External
Classifying
Seed
bed
With
External
Classifying
Seed
bed
Agitated
batch
Crystallizers
Other
Crystallizers

19. Agitated Batch Crystallizer
Principle:
Supersaturation by reducing the temp.
Agitation facilitates the production of uniform
size crystals.
Construction:
Cylindrical container with conical bottom.
Propeller attached with motor
Pipes for conducting heat.
Working:
Solution placed in crystallizer.
Cold water is passed through the pipes continuously.
Propeller is allowed to rotate.
Advantages:
Crystal formed are uniform & fine
Disadvantages:
Batch or discontinuous equipment
Crystals deposition is more on the pipes

20. Swenson Walker Crystallizer
Principle:
Passing the cold water in a direction opposite to the flow of hot concentrated solution.
Agitation prevents the accumulation of crystals.
Construction:
It linear type.
Long open trough with a semi-cylindrical bottom.
External water Jacket.
Long pitch spiral scrapper.
Working:
Solution fed at the left side of crystallizer & cooling water enters through other end.
Spiral scrapper rotates on its own axis helps in agitating the mixture & conveying of the crystals.
Advantages:
Crystal formed are uniform & Free from inclusions or aggregations
Continuous process.
Large saving in floor space, material & labour costs
Disadvantages:
Scrapper may break the crystals to a little extent.

21. Krystal Crystallizer Principle: Construction:
Concentration of liquid & crystallization are obtained in different chambers
Concentration (Supersaturation) induced by evaporation of hot solvent with the help of vacuum pump.
In the crystallization chamber the solution & crystals are maintained at fluidized state.
Construction:
Vapour Head - Long tube connected to pump.
Crystallization chamber

22. Krystal Crystallizer Working: Advantages: Disadvantages: Uses:
Used for large quantities of crystals of controlled size
Available in very large sizes.
Disadvantages:
Expensive
Uses:
Used for crystallization of NaCl C R Y S T A L
Vapour
Head
Vapours
Heater
Supersaturated solution
Flashing of Hot Solution
Solution
Hot solution

23. Vacuum Crystallizer Principle: Construction: Working: Advantages:
Supersaturation by adiabatic evaporative cooling.
Construction:
Cylindrical body with a conical bottom.
Condenser is attached to the crystallizer with a vacuum pump in between.
Propellers are placed above discharge pipe.
Working:
High vacuum is created using a vacuum pump.
Hot solution is fed into the crystallizer.
Solution undergo flashing results in evaporation of solvent.
Adiabatic cooling causes supersaturation & crystallization
Advantages:
Simple without any moving parts.
Corrosive materials can be used.
Can be constructed as large size as desired.
Can be operated batch wise or continuously.
Disadvantages:
Expensive
Uses:
Suitable for thermo labile substances, due to low temp conditions

24. THANK YOU !