Crystallization is the process in which solids are formed from a liquid or a gas phase. The direct gas-solid transformation is also known as desublimation or deposition. This form of crystallization is relatively rare in industrial use, but the formation of snow in clouds and the ice deposit after a cold night at your car window are well known examples deposition processes occurring in nature. Crystallization from the liquid occurs much more frequently and there are well-known examples from nature as well as from industry. Among the examples from nature are the formation of hailstones, gemstones and mineral deposits such as calcite stalactites in limestone caves. Well known, industrial applications of crystallization are amongst others sugar, salt, chocolate and soda ash, while a big portion of our pharmaceuticals have been crystallized at least one time (and often more) during their manufacturing.

Crystallization can sometimes be unwanted, like the formation of scaling or encrustation in waterworks at home and in industry, but in many cases crystallization is a controlled and wanted separation process in which crystals are formed in order to benefit from the high selectivity of the phase transition and/or to get particles with a size and/or shape that is important for further uses of the product. The extremely high selectivity of crystallization originated from the phenomenon that crystals are very regular structures in which building blocks like molecules, ions or atoms are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. Impurities will often have a different size and/or shape than the target product and will for this reason not fit in the crystal lattice. Therefore the impurities tend to stay in the liquid phase, whereas the crystals consist of almost completely the building blocks of the product. The crystals from a well-controlled crystallization step can easily have a 100-1000 times lower concentration of impurities than the liquid from which the crystals were grown and even after one crystallization process step the crystals can attain very high purities above 99+ wt% or even 99.9+ wt%. This explains why crystallization is as one of the most selective separation processes in chemical and other process industries. Crystallization is often used in processes were a significant purification and/or a high product purity is required.

Crystallization can be carried out as a continuous process as well as in batch. Large scale products like salt, soda ash or monomers for bulk plastics are typically made in a continuous process, whereas small scale products like pharmaceuticals are often made in a batch crystallization although during the last decade a clear shift to the use of continuous crystallization of pharmaceuticals can be noted due to the better control of process conditions, reproducibility and product quality that can be achieved in continuous crystallization.

Size and shape of crystals can be very important for the function because this can for instance influence the filterability, the drying behavior, the dissolution rate, the tableting properties, the ability to form stable suspensions or dispersions and the mixing with other (solid) ingredients. Crystallization is therefore also applied when a solid product is required with a specific size and/or shape.

Crystallization is a process with a broad applicability and for various uses. Different materials like metals, organics and inorganics can be crystalized. The internal structure of metals and/or metal alloys is determined by the same principles and processes that are known from the crystallization of organics and inorganics. The balance between nucleation, growth, attrition and agglomeration determines the size of the crystals. All these phenomena are somehow related to the supersaturation, which is the driving force for all crystallization processes. A crystallization can only occur when the liquid phase is supersaturated for one and more of the dissolved components. A supersaturated solution contains a higher concentration for one or more compounds than allowed by the equilibrium solubility of that/those compounds under the prevailing conditions. This equilibrium solubility can be derived from a solubility curve, which usually plots the solubility as a function of the temperature, or a phase diagram, which illustrates which phase(s) will crystallize as a function of the mixture composition and the temperature. A large number of solubility curves and phase diagrams have been published in open literature sources, but in case that the information required data cannot be found the solubility curve and/or the phase diagram have to measured experimentally. Nowadays, devices like the Crystal16 from Technobis[1] can help to determine solubility curves/phase diagrams faster by parallel screening of multiple samples/ and multiple conditions.

Supersaturation alone is not sufficient to start crystallization, because also the energy barrier of nucleation has to be surpassed. If that is not the case the supersaturated solution can remain metastable or undercooled. This means that the solution is supersaturated but not enough to form nuclei spontaneously. If seed crystals are added to a metastable or undercooled solution they will start to grow as there is no energy barrier for growth. The area in which nucleation does not occur spontaneously from a supersaturated a solution or melt is often called the metastable zone. The width of the metastable zone is not equal for all compounds it depends on properties of the compound as well as on the applied conditions, like the cooling rate.