2. CRYSTALLIZATION: Crystallization is important as an
industrial processbecause of the number of materials that are and
can bemarketed are in the form of crystals. Crystallization may be
carried out from a vapor, from amelt, or from a solution. More than
80% of the substances used inpharmaceuticals, fine chemicals,
agrochemicals, foodand cosmetics are isolated or formulated in
their solidform. Crystallization is in general the last chemical
purificationstep in the production of ingredients.
3. Crystallization is the (natural or artificial) process
offormation of solid crystals precipitating from a solution,melt or
more rarely deposited directly from a gas. Crystallization is also
a chemical solid-liquid separationtechnique, in which mass transfer
of a solute from theliquid solution to a pure solid crystalline
phase occurs. Its extensive use is based on the fact that this
singleoperation is both a separation and a purification
processwhereby a solid crystalline product can be isolated withhigh
purity and with relatively low capital and operatingcosts.
4. Crystals A crystal may be defined as a solid composed of
atoms arrangedin an orderly, repetitive array. Crystals are grown
in many shapes, which are dependent upondownstream processing or
final product requirements Crystal shapes can includecubic,
tetragonal, orthorhombic, hexagonal, monoclinic, triclinic, and
trigonal. In order for crystallization to take place a solution
must be"supersaturated". Supersaturation refers to a state in which
the liquid (solvent)contains more dissolved solids (solute) than
can ordinarily beaccomodated at that temperature The
crystallization process consists of two majorevents, nucleation and
crystal growth.
5. Nucleation Nucleation is the step where the solute molecules
dispersedin the solvent start to gather into clusters, on
thenanometer scale (elevating solute concentration in a
smallregion), that becomes stable under the current
operatingconditions. the clusters reach a critical size in order to
become stablenuclei.This is dictated by the operating
conditions(temperature, supersaturation, etc) Total nucleation is
the sum effect of two categories ofnucleation - primary and
secondary.
6. Primary nucleation Primary nucleation is the initial
formation of a crystalwhere there are no other crystals present or
where, ifthere are crystals present in the system, they do nothave
any influence on the process. This can occur in two conditions:1.
homogeneous nucleation2. heterogeneous nucleation
7. Secondary nucleation Secondary nucleation is the formation
of nucleiattributable to the influence of the existingmicroscopic
crystals in the magma. first type of known secondary
crystallization isattributable to fluid shear, the other due to
collisionsbetween already existing crystals with either a
solidsurface of the crystallizer or with other
crystalsthemselves.
8. Crystal growth Once the first small crystal, the nucleus,
forms itacts as a convergence point for molecules of solutetouching
- or adjacent to - the crystal so that itincreases its own
dimension in successive layers. Growth rate is influenced by
several physicalfactors, such as surface tension ofsolution,
pressure, temperature, relative crystalvelocity in the
solution.
9. Artificial methods For crystallization to occur from a
solution it must besupersaturated This can be achieved by various
methods:1. solution cooling,2. addition of a second solvent to
reduce the solubility ofthe solute3. chemical reaction4. solvent
evaporation
10. Applications There are two major groups of applications for
theartificialcrystallization process:1. crystal production and2.
purification.
11. Equipment for crystallization Tank Crystallizers Forced
circulation crystallizer Scraped surface crystallizers
Circulating-magma vacuum crystallizer Oslo crystallizer
12. DTB (Draft Tube and Baffle) crystallizer
13. Oslo-Krystal Cooling crystallizers
14. Whole broth processing The concept of recovering a
metabolite directly froman unfiltered fermentation broth is of
considerableinterest because of its simplicity, the reduction
inprocess stages and the potential cost savings. It may also be
possible to remove the desiredfermentation product continuously
from a brothduring fermentation so that inhibitory effects due
toproduct formation and product degradation can beminimized
throughout the production phase.
15. Methods Ion exchange resins Dialysis Expanded-Bed
Adsorption Resin method.
16. Ion exchange resins Ion exchange resins are polymers that
are capable of exchangingparticular ions within the polymer with
ions in a solution that ispassed through them The resins are
prepared as spherical beads 0.5 to 1.0 mm in diameter. These appear
solid even under the microscope, but on a molecular scalethe
structure is quite open. This means that a solution passed down a
resin bed can flow throughthe crosslinked polymer, bringing it into
intimate contact with theexchange sites.
17. Dialysis Removal of soluble impurities from solution by the
useof semipermeable membrane is known as dialysis Solutes present
in a solution(broth) can pass througha semipermeable membrane.
Cycloheximide was extracted using methylenechloride. Methylene
chloride was circulated in adialysis tubing loop which passed
through afermentor. The product yield increased by almost double by
thisdialysis-solvent extraction method.
18. Resin Method Sterile beads of an acrylic resin, as
dispersed beadsor beads wrapped in ultrafiltration method, wereput
in fermentors 48 hours after inoculation. Some of the cycloheximide
formed in broth wasabsorbed in resin. Recovery of antibiotic from
resin is achieved bysolvents or by changing temperature.
19. Electrodialysis(ED) Electrodialysis(ED) is a well known
separationprocess where ionized compounds are separated fromnon
ionized compounds in aqueous solutions based ontransport through
ion exchange membranes in anelectric field. Since in a fermentation
broth the lactate salt isionized, whereas the carbohydrates and
proteins andamino acids are either non ionized or weakly
ionized,recovery and purification of lactate salts from
afermentation broth by electrodialysis is feasible.
20. Expanded-Bed Adsorption TheoryExpanded-Bed Adsorption
TheoryWhen the resin has packed in the column, the beads are close
together (1). As thecolumn is fluidized, the resin beads establish
a concentration gradient (2). The samplefeedlot is injected, and
particulates and cell debris (green dots) move past the resin
andout of the column, while the compound of interest (red dots)
interacts with the beads(3). The column is then repacked, the flow
is reversed, and the compound is elutedfrom the beads (4).