Principles Underlying the Design and Operation of Crystallizers

| Home | | Pharmaceutical Technology |

Chapter: Pharmaceutical Engineering: Crystallization

The purpose of a crystallization plant is to produce, as far as possible, crystals of the required shape, size distribution, purity, and yield.


The purpose of a crystallization plant is to produce, as far as possible, crystals of the required shape, size distribution, purity, and yield. This is achieved by maintaining a degree of supersaturation at which nucleation and crystal growth proceed at appropriate rates. Control of the number of nuclei formed controls the size of the crystals deposited from a given quantity of solution. Alter-natively, crystal number and size can be controlled by adding the correct amount of artificial nuclei or seeds to a system in which little or no natural nucleation is taking place.

In the majority of cases, the mode of operation is determined by the relation between the solubility of the solute and the temperature, examples of which are shown in Figure 9.4. This determines how supersaturation is to be achieved. Other factors of importance are the thermal stability of the solute, the impurities that may be present, and the degree of hydration required. If the solubility of the solute increases greatly with temperature, supersaturation and deposition of a large proportion of the solute are brought about by cooling a hot concentrated solution. Sodium nitrate provides an example. Sodium chloride and calcium acetate, on the other hand, exemplify materials with a small or negative temperature coefficient of solubility. Here, supersaturation can best be achieved by evaporating a part of the solvent. In some cases, both evaporation and cooling are employed. The mother liquors following evapo-rative crystallization can be cooled to yield a further crop of crystals provided there is a suitable change in solubility and impurities present do not prohibit the process. In other crystallizers, flash cooling is used. A hot solution is passed into a vacuum chamber in which both evaporation and cooling take place.

Supersaturation can also be induced by the addition of a third substance that reduces the solubility of a solute in a solvent. These precipitation processes, which are important in the processing of thermolabile materials, are controlled by the temperature of mixing, the agitation, and the rate at which the third substance is added. Water-insoluble materials dissolved in water-miscible organic solvents can be precipitated by adding water. Alternatively, the aqueous solubility of many materials can be reduced by the change of pH or by the addition of a common ion. Proteins can be salted out of solution by the addition of ammonium chloride and adjustment of pH. Finally, precipitation of a crys-talline solid may be the result of a chemical reaction.

A crystallizer should produce crystals of uniform particle size. This facilitates removal of the mother liquor and washing. If large quantities of the liquor are occluded in the mass of crystals, drying will yield an impure product. In addition, crystals of even size are less likely to cake on storage.

Contact Us, Privacy Policy, Terms and Compliant, DMCA Policy and Compliant

TH 2019 - 2024; Developed by Therithal info.