Transcript CRYSTALLIZATION Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics Faculty of Pharmacy Omer Al-Mukhtar University Tobruk, Libya. E-mail: [email protected] 2014/05/13 Faculty of Pharmacy, Omer Al-Mukhtar University, Tobruk,

CRYSTALLIZATION
Dr. Basavaraj K. Nanjwade
M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: [email protected]
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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CONTENTS
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Mier’s super saturation theory
Factor affecting crystallization
Continuous crystallizers
Cooling crystallizers
Evaporative crystallizers
References
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Crystallization
• Definition: Crystallization is the spontaneous
arrangement of the molecules into regular geometric
form supersaturated solution.
• Some times crystallization can also take place directly
from vapour of the substances, such process is known
as ‘SUBLIMATION’.
Example:
1. Solid camphor from camphor vapour
2. Solid iodine from Iodine vapour
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Applications of crystallization
process
1. Purification of drugs
2. Better
processing
characteristics
such
as
compressibility and wettability of drugs.
3. Easy handing transport and storage.
4. Improve the stability of various drugs.
5. Improve the bioavailability.
6. Drugs in different crystal form used in the
production of certain sustained release dosage
forms.
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Mier’s super saturation theory
• Mier’s theory of supersaturation states that a definite
relationship between concentration and temperature at
crystals which will form spontaneously in an
unseeded solution.
• Curve AB indicates normal solubility, that means at
any point the solute is in equilibrium with solute.
• Cure FG indicates super solubility which is parallel to
the normal solubility, it also represents the limit at
which nucleus formation begins.
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Mier’s super saturation theory
Formation of crystals
A plot of temperature versus concentration of solute
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Mier’s super saturation theory
• Metastable state indicates, unstable and undergoes
changes and it is enclosed between the curves AB and
FG.
• Consider a point ‘C’ near solubility curve, with
definite composition and temperature, crystallization
is expected to start from point ‘P’ but it does not
occur.
• According to theory, crystallization takes place after
point ‘P’ somewhere in the neighbour of the point ‘D’
when certain conditions are specified.
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Factor affecting crystallization
1. Solvent Considerations: Moderate solubility is best.
Supersaturation leads to sudden precipitation and smaller
crystal size.
2. Nucleation & Growth: Fewer nucleation sites are better. Too
many nucleation sites (i.e. dust, hairs, etc.) lower the average
crystal size.
3. Mechanics (Crystal Growth): mechanical disturbances are
bad.
4. Time: Faster crystallization is not as good as slow
crystallization. Faster crystallization higher chance of lower
quality crystals.
5. Crystal Growing Techniques: Slow Evaporation, Slow
Cooling, Variations
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Continuous crystallizers
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Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Cooling crystallizers
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Cooling crystallizers
• Concentrated solution gradually cooled below
saturation temperature (50-60°C) to generate a
supersaturated state.
• Yields well defined micron-sized crystals.
• Shell and tube heat exchanger is used to cool
solution.
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Cooling crystallizers
• Advantages:
– High purity downstream
• Disadvantages:
– Temperature change does not always have a positive effect
on supersaturation in proteins
– Protein stability may be at risk
– Solubility can be relatively insensitive to temperature at
high salt concentrations
– Cooling will only help reach supersaturation in systems
where solubility and temperature are directly related
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
12
Evaporative crystallizers
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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Evaporative crystallizers
• Solute dissolves in solution when heated to a certain
temperature (75°C).
• Slowly cooled until crystals precipitate.
• Shell and tube heat exchanger is used to heat and cool
solution.
• Advantages:
– high purity levels downstream
• Disadvantages:
– Vaporization chamber requires high pressures
– Protein viability very sensitive to high temperatures
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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E-mail: [email protected]
2014/05/13
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
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