47805741 crystallization-whole-broth-processing


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47805741 crystallization-whole-broth-processing

  1. 1. Submitted by:Rouf AhmadCrystallization & Whole brothprocessing
  2. 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. 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. 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. 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. 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. 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. 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. 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. 10. Applications There are two major groups of applications for theartificialcrystallization process:1. crystal production and2. purification.
  11. 11. Equipment for crystallization Tank Crystallizers Forced circulation crystallizer Scraped surface crystallizers Circulating-magma vacuum crystallizer Oslo crystallizer
  12. 12. DTB (Draft Tube and Baffle) crystallizer
  13. 13. Oslo-Krystal Cooling crystallizers
  14. 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. 15. Methods Ion exchange resins Dialysis Expanded-Bed Adsorption Resin method.
  16. 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. 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. 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. 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. 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).