The metastable zone refers to a specific region in the phase diagram of a substance where a solution or melt can exist temporarily in a state that is thermodynamically unstable. In this zone, the substance remains in a supersaturated or supercooled state, meaning it contains a higher concentration of solute or is at a lower temperature than its equilibrium state would typically allow.
Within the metastable zone, the solution or melt is in a state of kinetic stability rather than thermodynamic stability. This means that although the system is not in its most energetically favorable state, it can persist in this state due to the absence of nucleation or crystallization triggers.
The metastable zone is important in processes such as crystallization, where controlling the formation and growth of crystals is desired. By operating within the metastable zone, it is possible to induce controlled nucleation and subsequent crystal growth, leading to the formation of desired crystal structures with specific properties.
However, it is crucial to carefully navigate the metastable zone since any disturbances or external factors can trigger nucleation and rapid crystal formation, leading to an undesired outcome. Therefore, understanding the boundaries of the metastable zone and implementing appropriate control strategies are essential in optimizing processes such as crystallization, precipitation, or supercooling.
One way to determine the metastable zone is by utilizing a probe-based optical instrument like ParticleTrack. This instrument monitors the changes in particle size and counts during a process. By accurately identifying the point of dissolution on the solubility curve and the point of nucleation within the metastable zone at different solute concentrations, ParticleTrack enables the measurement of both the solubility curve and the metastable zone width (MSZW).
In a study conducted by Barrett and Glennon (Trans ICHemE, vol. 80, 2002, pp. 799-805), an unsaturated solution is gradually cooled at a consistent rate. Using ParticleTrack with FBRM, the point of nucleation within the metastable zone is determined, indicating a specific position within the MSZW. Subsequently, the solution is slowly heated until the point of dissolution is measured, marking a point on the solubility curve. This process is repeated by adding solvent to reduce the concentration, allowing for a swift measurement of the solubility curve and MSZW over a wide range of temperatures.
Recrystallization is a technique used to purify solid compounds by dissolving them in a hot solvent and allowing the solution to cool. During this process, the compound forms pure crystals as the solvent cools, while impurities are excluded. The crystals are then collected, washed, and dried, resulting in a purified solid product. Recrystallization is an essential method for achieving high levels of purity in solid compounds.
Solubility curves are commonly used to illustrate the relationship between solubility, temperature, and solvent type. By plotting temperature vs. solubility, scientists can create the framework needed to develop the desired crystallization process. Once an appropriate solvent is chosen, the solubility curve becomes a critical tool for the development of an effective crystallization process.
Supersaturation occurs when a solution contains more solute than should be possible thermodynamically, given the conditions of the system. Supersaturation is considered a major driver for crystallization
In-process probe-based technologies are applied to track particle size and shape changes at full concentration with no dilution or extraction necessary. By tracking the rate and degree of change to particles and crystals in real time, the correct process parameters for crystallization performance can be optimized.
Seeding is one of the most critical steps in optimizing crystallization behavior. When designing a seeding strategy, parameters such as seed size, seed loading (mass), and seed addition temperature must be considered. These parameters are generally optimized based on process kinetics and the desired final particle properties, and must remain consistent during scale-up and technology transfer.
Liquid-Liquid phase separation, or oiling out, is an often difficult to detect particle mechanism that can occur during crystallization processes.
In an antisolvent crystallization, the solvent addition rate, addition location and mixing impact local supersaturation in a vessel or pipeline. Scientists and engineers modify crystal size and count by adjusting antisolvent addition protocol and the level of supersaturation.
Crystallization kinetics are characterized in terms of two dominant processes, nucleation kinetics and growth kinetics, occurring during crystallization from solution. Nucleation kinetics describe the rate of formation of a stable nuclei. Growth kinetics define the rate at which a stable nuclei grows to a macroscopic crystal. Advanced techniques offer temperature control to modify supersaturation and crystal size and shape.
Changing the scale or mixing conditions in a crystallizer can directly impact the kinetics of the crystallization process and the final crystal size. Heat and mass transfer effects are important to consider for cooling and antisolvent systems respectively, where temperature or concentration gradients can produce inhomogeneity in the prevailing level of supersaturation.
Crystal polymorphism describes the ability of one chemical compound to crystallize in multiple unit cell configurations, which often show different physical properties.
Protein crystallization is the act and method of creating structured, ordered lattices for often-complex macromolecules.
Lactose crystallization is an industrial practice to separate lactose from whey solutions via controlled crystallization.
The MSMPR (Mixed Suspension Mixed Product Removal) crystallizer is a type of crystallizer used in industrial processes to produce high-purity crystals.
A well-designed batch crystallization process is one that can be scaled successfully to production scale - giving the desired crystal size distribution, yield, form and purity. Batch crystallization optimization requires maintaining adequate control of the crystallizer temperature (or solvent composition).
Continuous crystallization is made possible by advances in process modeling and crystallizer design, which leverage the ability to control crystal size distribution in real time by directly monitoring the crystal population.