Offline analysis is commonly used to determine crystal distribution at the end of an experiment or during a production run. While such an approach is common, there are limitations to offline analysis which are relevant for crystals:
This set of ParticleView images neatly illustrates the complex size, shape, and structure of various crystals. From large round “boulders” to beautifully delicate “dendrites”, crystal product is often varied, posing challenges to effective separation and downstream manipulation.
By studying crystals in real time, scientists can develop detailed and reliable process understanding on a routine basis. ParticleView V19 with PVM technology allows scientists to directly observe crystals and crystal structures in process without having to take a sample.
Crystallization mechanisms such as nucleation, growth, breakage, and shape changes can be observed under dynamic changing process conditions and the most suitable process parameters can be chosen with confidence. A simple image-based trend that indicates how crystal size, shape, and count complements high resolution real time images and allows important process events to be identified and investigated immediately.
Using ParticleTrack, scientists can:
A ParticleTrack probe with FBRM technology is immersed into a flowing slurry or droplet system with no dilution necessary. A focused laser scans the surface of the probe window and tracks individual chord lengths - measurements of particle size, shape, and count. This real-time measurement is presented as a distribution and statistics (eg. mean, counts) are trended over time.
Crystallization unit operations offer the unique opportunity to target and control an optimized crystal size and shape distribution. Doing so can dramatically reduce filtration and drying times, avoid storage, transport, and shelf life issues, and ensure a consistent and repeatable process at a lower cost.
This white paper series covers basic and advanced strategies to optimize crystal size and shape distribution.
Discover how image-based process trending can reduce crystallization cycle time and improve quality while maintaining a similar crystal size and shape.
This white paper discusses best practices for designing a seeding strategy and what parameters should be considered when implementing a seeding protocol. Although crystallization understanding has improved over the last thirty years, the seeding step still presents challenges.
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 protocol is most important in producing a crystal product of consistent quality. Seeding a batch crystallization is used to control the nucleation event and minimize batch to batch variability.
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.
Polimorfizm jest powszechnym zjawiskiem w wielu krystalicznych ciałach stałych w przemyśle farmaceutycznym i chemicznym. Naukowcy celowo krystalizują pożądany polimorf, aby poprawić właściwości izolacyjne, pomóc w przezwyciężeniu wyzwań związanych z procesem dalszego przetwarzania, zwiększyć dostępność biologiczną lub zapobiec konfliktom patentowym. Identyfikacja transformacji polimorficznych i morfologicznych in situ i w czasie rzeczywistym eliminuje występowanie nieoczekiwanych zakłóceń procesu oraz zapobiega odbieganiu produktu od specyfikacji i zabezpiecza przed kosztownym ponownym przetwarzaniem materiału.
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.
Dobrze zaprojektowany cykliczny proces krystalizacji jest jednym z tych procesów, który może być z powodzeniem skalowany do skali przemysłowej – dając pożądany rozkład wielkości, uzysk, formę i czystość kryształów.
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.
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.
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.
Polimorfizm jest powszechnym zjawiskiem w wielu krystalicznych ciałach stałych w przemyśle farmaceutycznym i chemicznym. Naukowcy celowo krystalizują pożądany polimorf, aby poprawić właściwości izolacyjne, pomóc w przezwyciężeniu wyzwań związanych z procesem dalszego przetwarzania, zwiększyć dostępność biologiczną lub zapobiec konfliktom patentowym. Identyfikacja transformacji polimorficznych i morfologicznych in situ i w czasie rzeczywistym eliminuje występowanie nieoczekiwanych zakłóceń procesu oraz zapobiega odbieganiu produktu od specyfikacji i zabezpiecza przed kosztownym ponownym przetwarzaniem materiału.