crystalization of various substances 2.pptx

Crystallization

1. Crystallization Name: shrddhaba j chudasama Sub: pharmaceutical process chemistry Enroll: 202280822007 Department: pharmaceutical chemistry L.M College of pharmacy,Navrangpura Ahmedabad .

2. Definition and understanding Crystallization refers to the formation of solid particles from a vapour, the solidification from a liquid melt or the formation of dispersed solids from a solution. Crystallization , incorporating wider definition to include precipitation and solid-state transitions, is a major technological process for particle formation in pharmaceutical industry  . It is estimated that over 70% of all solid materials are produced by crystallization. ....

3. Mechanism of crystallization The formation of crystals from solution involve three step: 1. Super saturation 2. Nucleus formation 3. Crystal growth Mechanism of Crystallization. In this in the second steps there was further types of nucleation divided in to two primary and secondary and primary further divided in to two (a) heterogeneous nucleation (b) homogenous nucleation

4. 1) Supersaturation:The solubility of a compound In a solvent exceeds the saturation solubility , the solution becomes supersaturated and the compound may precipitate or crystallize. Supersaturation can be achieved.

5. Mechanism of crystallization Nucleation refers to the birth of very small bodies of new phase with In a homogenous supersaturated liquid phase. If all sources of partition are subsumed under the term nucleation, a number of kinds of nucleation may occur. They divided in to two types (1) primary nucleation (2) secondary nucleation.

6. Nucleation (1) Primary nucleation The phenomenon of the nucleation is the same for crystallization from the solution , crystallization from a melt , condensation of fog drops in a super cooled vapour and generation of bubble In a supersaturated liquid. There are two types a) Homogeneous nucleation b) Heterogeneous nucleation

7. Homogeneous nucleation is used to describe precipitates that form at random in a perfect lattice. True homogeneous nucleation that is independent of any lattice defect is very rare. Homogeneous nucleation can only become viable if the strain energy and surface energy involved in creating a nucleus are small.

8. Homogenous nucleation There are, however, many important age hardening phases that do not develop at dislocations, grain boundaries, or interfaces, and precipitate homogeneously throughout the grain interiors.  Typically, the phases involved are metastable and the precipitation occurs at low temperatures and large supersaturations. In aluminium alloys the majority of these phases develop from solute clusters, or GP zones (GPZs), by spinodal decomposition, and involve strong interactions with vacancies .

9. Homogenous nucleation For example, recent atom probe investigations of precipitation in Al–Cu–Mg and Al–Mg–Si alloys have shown that initially separate elemental clusters are formed and this is followed by co-clustering of alloying elements from which GPZs form and transition phases nucleate .

10. Homogenous nucleation Solute clustering and GPZ formation results in a natural aging response. This is a technologically important property of some aluminium alloys as it allows them to be formable in the solution treated condition and then strengthen with time at room temperature after fabrication.

11. Homogenous nucleation In aluminium alloys, generally, “homogeneously nucleated” phases evolve from solute clusters and GPZs formed during the low-temperature decomposition of the solid solution. The excess vacancies quenched by rapid cooling following solution treatment play an important role in solute clustering and GPZ formation. Excess vacancies significantly increase the diffusion rate and facilitate the formation of solute clusters by relieving misfit strains.

12. Heterogeneous nucleation : If effect holds that if the nucleus wets the surface of the catalyst ,then nucleation formation is reduced by a factor that is a function of the angle of wetting between the nucleus and the catalyst .

13. Heterogeneous nucleation Many phase transformations take place heterogeneously in the solid state. Grain boundaries are favoured sites for such reactions because excess interfacial energy is available there for nucleation of new phases. This is why proeutectoid phases like α-Fe and Fe 3 C, as well as two-phase mixtures of pearlite, nucleate at prior austenite grain boundaries. Precipitates and inclusions in the matrix also serve as heterogeneous nucleation sites.

14. Secondary nucleation Secondary nucleation is the formation of nuclei attributable to the influence of the existing microscopic crystals in the magma. Simply put, secondary nucleation is when crystal growth is initiated with contact of other existing crystals or “seeds”.  The first type of known secondary crystallization is attributable to fluid shear, the other due to collisions between already existing crystals with either a solid surface of the crystallizer or with other crystals themselves. Fluid-shear nucleation occurs when liquid travels across a crystal at a high speed, sweeping away nuclei that would otherwise be incorporated in to a crystal, causing the swept-away nuclei to become new crystals. Contact nucleation has been found to be the most effective and common method for nucleation. The benefits include the following.

15. Secondary nucleation Low kinetic order and rate-proportional to supersaturation, allowing easy control without unstable operation. Occurs at low supersaturation, where growth rate is optimal for good quality. The quantitative fundamentals have already been isolated and are being incorporated into practice.

16. Crystal growth Once the first small crystal, the nucleus, forms it acts as a convergence point (if unstable due to supersaturation) for molecules of solute touching or adjacent to the crystal so that it increases its own dimension in successive layers. The supersaturated solute mass the original nucleus may  capture  in a time unit is called the  growth rate  expressed in kg/(m 2 *h), and is a constant specific to the process.

17. Factors affecting Crystal growth Growth rate is influenced by several physical factors, such as surface tension  of solution , pressure, temperature, relative crystal velocity in the solution, Reynolds number, and so forth.

18. Factors affecting crystallization Both formation of nuclei and occurring of crystallization affected by the nature of the substances factors like temperature,concentration,agitation, and impurities present in the solution etc. (1) Nature of crystallizing substance:Nature of the crystallizing substance: Some substances like salt crystallize readily from water solution. It requires only a very slight super-saturation to start nuclear formation, and all excess salt in the solution beyond the saturation point is precipitated as crystals. Some substances do not form nuclei or crystallize so readily as salt. With sucrose it is often necessary to have a considerable degree of supersaturation before crystallization commences. Sucrose crystallizes more readily than levulose.

19. Factors (2)Formation of nuclei: Nuclei cannot form and crystallization cannot occur except from a supersaturated solution. The formation of nuclei, that is the uniting of atoms to form nuclei, is influenced by several factors. If a solution is left to stand, a few nuclei may form spontaneously in various places, and from these nuclei crystallization proceeds. When only a few nuclei develop spontaneously in the solution, the crystals grow to large size. Usually nuclei formation and crystallization do not begin immediately after supersaturation occurs.

20. Factors The rate of nuclear formation may be favoured by specks of dust in the solution. Agitation or stirring of a solution increases the rate of nuclear formation. A drop in temperature at first favours, and then retards, the formation of nuclei. Instead of spontaneous formation of nuclei, seeding a solution may be used to start crystallization.

21. Factors Seeding: When crystals of the same material are added to start crystallization the process is called seeding. These crystals serve as nuclei for crystal growth. If the quantity of crystals added is large and the size of the crystals small, it serves as many nuclei in the solution and the resulting crystals are small. If the quantity of material added is very small, the nuclei formed are few in number and the crystals formed are large. One may think of all crystals as being large enough to be visible, whereas many of them may be very small, so small in fact that they may float in the air. If crystals are floating in the air there is the possibility that they may serve to seed solutions, and thus start crystallization.

22. Factors Rate of crystallization: To the nuclei formed in the solution new molecules from the solution are deposited, in a regular order or manner, so that each crystal has a typical shape. One side or face of a crystal may grow more rapidly than another. The rate at which the nuclei grow to larger size is called the rate of crystallization. This rate may be favoured by the concentration of the solution and its temperature; it may be hindered by foreign substances.

23. Factors Concentration of the solution: A more concentrated solution favours the formation of nuclei. Fondant syrup cooked to 114°C. Contains less water and is more concentrated than one cooked to 111°C. Thus nuclei form more readily in the one cooked to 114°C. Large, well-shaped crystals form more readily if the degree of supersaturation is not too great. The most favourable supersaturation for crystal growth, of a sucrose solution boiled to 112°C, is that between 70° and 90°C. Although crystallization occurs in a very short time when the syrup is stirred at these temperatures, the crystals formed are larger than when the syrup is cooled to a lower temperature. Supersaturation and a low temperature are desirable for the development of small crystals.

24. Factors Temperature at which crystallization occurs: It is a well-known fact that, in general, chemical precipitates come down more coarsely crystalline if crystallized at high temperatures. The sugars follow this general rule. Other things being equal, concentration, etc., the higher the temperature at which crystal formation occurs, the coarser the crystals formed.

25. Factors A drop in temperature at first favours the formation of nuclei, and then hinders it. Crystallization is favoured in sugar syrups by cooling to a certain temperature, but is hindered when cooled to a lower temperature. Since the viscosity of a saturated sugar solution becomes increasingly greater as the temperature falls below 70°C, crystal formation is also slower as the temperature falls.

26. Factors Agitation: Stirring a solution favours the formation of nuclei and hinders the depositing of the material of the solution on the nuclei already formed. Hence, crystals in solutions that are stirred do not develop to the size that they do in spontaneous crystallization. If small crystals are desired, then the conditions should be such that many nuclei are formed. Small crystals are obtained in syrups of definite concentration and temperature, if the syrup is stirred until the mass is kneadable.

27. Factors However, if the syrup is stirred for only a short time, some nuclei are formed, but after agitation is stopped, the formation of new nuclei is not favoured and crystal growth is favoured. This emphasizes the importance of stirring candy and icing syrups until practically all the material is crystallized, if small crystals are desired. Impurities in the sugar syrup may also result in the formation large sugar crystals. Impurities promote premature crystal formation, which will grow to big unwanted crystals.

28. Crystallization form non aqueous forms Crystallization from non- aqueous solution. Growth of non aqueous solutions often allows realization of special crystallization aims by control of the solution properties. Solvents are classified to further understand solubility of electrolytes and non electrolytes. Several solvents and solubility effects are then pointed out such as the effect on the nucleation , which is easier when solubility is higher ion the crystallization of polymorph and on the surface morphology of the crystals.

29. Form Non aqueous solvent Solvent also change growth rate altering properties of the adsorption layer. In non electrolyte solution , the molecules of the solute are not dissociate during that dissolution process. SOLVENT AND SOLUILITY: With the use of non aqueous solvent it is sometime possible to fit the solvent-solute system to some aims such as modification of habit and morphology or even simple use of high low solute concentration.

30. Form Non aqueous solvent There are three main classes of solvents: 1. Hydrogen donors ( methanol, formamide)are protic solvents. 2. dipolar aprotic solvents (acetonitrile , nitrobenzene). 3. If the dielectric constant is weak , the solvent is non- polar aprotic (pentane, benzene)

31. Form Aqueous solvents Crystallization of aqueous solvent Water of crystallization are water molecules that are present inside the crystals. Water is often incorporated in the formation of crystals from aqueous solution. Water of crystallization is the total mass of water in a substance at a given temperature and is mostly present define ration. Water of crystallization refers to water that is found in the crystalline framework of metal complex or a salt, which is not directly bonded to the metal cation.

32. Form non aqueous solvent Water of crystallization can generally be removed by heating a sample but the crystalline properties are often lost. Ex. In case of sodium chloride, the dehydrate unstable at room temperature compared to inorganic salts , proteins crystallize with large amount of water in the crystal lattice.

33. Summery

34. References technolwww.researchgate.net/publication/222800531_Crystallization_Processes_in_Pharmaceutical_Technologyogy/ crystallizationhttps :// Drug_Delivery_Design https :// pubs.rsc.org /en/content/ articlelanding /2018/CC/c8cc02381f#! divAbstract

35. Reference https://www.jbc.org/article/S0021-9258(20)72585-8/fulltext https://www.sciencedirect.com/topics/engineering/homogeneous-nucleation https://www.allfordrugs.com/crystallization/ https://www.slideshare.net/ShikhaPopali1/crystallization-easily-described

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