Metastable Zone Width Crystallization

Metastable Zone Width (MSZW) in Crystallization

The Building Blocks of Crystallization

Zadzwoń

What Is Metastable Zone?

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.

metastable zone graphs

How Do You Determine the Metastable Zone?

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.

Crystallization Development
Reduce Solubility of Product in Saturated Starting Solution
Importance of Solubility Curves
How To Measure Solubility
Solubility and Metastable Zone Width Determination Case Studies
Solubility and Metastable Zone Width Determination Technologies
Crystallization and Precipitation
Crystallization Academy
Crystallization Image Analysis

Aplikacje

Building Blocks of Crystallization Applications

Recrystallization
Optimization of Crystal Properties and Process Performance

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.

Metastable Zone Width (mzw) Determination
The Building Blocks of Crystallization

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
The Driving Force For Crystallization

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

Measure Crystal Size Distribution
Improve Crystallization with Inline Particle Size, Shape, and Count Measurement

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.

Badania nad zarodkowaniem krystalizacji i optymalizacja
Projektowanie i optymalizacja protokołu zarodkowania w celu zapewnienia lepszej powtarzalności krystalizacji

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.

Oiling Out in Crystallization
Detect and Prevent Oiling Out (Liquid-Liquid Phase Separation)

Liquid-Liquid phase separation, or oiling out, is an often difficult to detect particle mechanism that can occur during crystallization processes.

Anti-Solvent Addition on Supersaturation
How Solvent Addition Can Control Crystal Size and Count

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.

Temperature Effects Crystallization Size and Shape
Supersaturation Control Optimizes Crystal Size and Shape

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.

Temperature Effects Crystallization Size and Shape
Scaling-Up Agitation, Dosing, and Crystallization

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
Zrozumienie polimorfizmu i wpływu parametrów procesu

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
Create Structured, Ordered Lattices for Complex Macromolecules

Protein crystallization is the act and method of creating structured, ordered lattices for often-complex macromolecules.

Lactose Crystallization
Recover Lactose with High Yield and Scalable Process

Lactose crystallization is an industrial practice to separate lactose from whey solutions via controlled crystallization.

Optymalizacja i skalowanie krystalizacji cyklicznej
Osiągaj stan przesycenia i określaj produkt końcowy mający strukturę krystaliczną

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.

Krystalizacja ciągła – monitorowanie i kontrola
Monitorowanie w czasie rzeczywistym przesycenia i populacji kryształów w celu modelowania i kontroli procesu krystalizacji prowadzonego w trybie ciągłym

Recrystallization

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.

Metastable Zone Width (mzw) Determination

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

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

Measure Crystal Size Distribution

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.

Badania nad zarodkowaniem krystalizacji i optymalizacja

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.

Oiling Out in Crystallization

Liquid-Liquid phase separation, or oiling out, is an often difficult to detect particle mechanism that can occur during crystallization processes.

Anti-Solvent Addition on Supersaturation

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.

Temperature Effects Crystallization Size and Shape

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.

Temperature Effects Crystallization 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

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

Protein crystallization is the act and method of creating structured, ordered lattices for often-complex macromolecules.

Lactose Crystallization

Lactose crystallization is an industrial practice to separate lactose from whey solutions via controlled crystallization.

Optymalizacja i skalowanie krystalizacji cyklicznej

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.

Biblioteka

Publications On the Building Blocks of Crystallization

White Papers

Zrozumienie krystalizacji dzięki mikroskopii in situ
Mechanizmy dynamiczne stanowiące klucz do zrozumienia procesów krystalizacji można teraz swobodnie obserwować, wykorzystując mikroskopię in situ. W pr...
opracowanie skutecznego procesu krystalizacji
Jakość procesu krystalizacji w istotnym stopniu wpływa na jakość produktu gotowego. W naszym nowym przewodniku omówiliśmy podstawy krystalizacji i pod...
Strategie kontroli rozkładu wielkości kryształów
Substancje stosowane w przemyśle farmaceutycznym i substancje wysokowartościowe muszą często przechodzić przez wiele etapów krystalizacji w procesach...
Usprawnij krystalizację realizowaną na skalę przemysłową
Krystalizacja jest ważnym etapem oddzielania i oczyszczania w przemyśle chemicznym. W przewodniku zaprezentowano sposób wykorzystania technologii śled...
Zaszczepianie procesu krystalizacji
Zaszczepianie jest kluczowym etapem, który pozwala optymalizować proces krystalizacji, dzięki czemu osiąga się powtarzalną szybkość filtrowania, uzysk...
Skalowanie procesu krystalizacji. Od skali laboratoryjnej do skali przemysłowej
Monitorowanie w czasie rzeczywistym procesu krystalizacji dostarcza szereg korzyści, zapewniając lepsze metody rozwoju, optymalizacji i skalowania pro...
najlepsze praktyki podczas opracowania procesu krystalizacji
W przewodniku omówiono metodologię wykorzystywaną przez chemików do optymalizacji kluczowych parametrów krystalizacji takich jak: Profil temperaturowy...
Charakteryzowanie cząstek — od małych reaktorów laboratoryjnych po pełnowymiarowe procesy przemysłowe
Techniki analizy wielkości cząstek są stosowane w celu zapewnienia wysokiej jakości produktów zawierających cząstki. Połączenie analizatorów wielkośc...

Webinars

Continuous Flow Chemistry Using PAT
Eric Fang of Snapdragon discusses how continuous flow chemistry is applicable across the entire value chain. Early implementation of continuous flow...
Eliminating Micronization Using Fine Particle Crystallization
Crystal engineering is applied when the crystal size distribution is too large to meet downstream specifications. By designing the crystallization to...
Calibration Free Supersaturation Assessment
The quantitative use of in situ ATR-FTIR for real time supersaturation assessment has been extremely well defined within the literature. However, thes...
metastable zone width (MSZW) crystallization
The webinar focuses on a semi-quantitative method for the optimization and scale-up of hydrodynamically limited anti-solvent crystallization process....
Improving Crystallization and Precipitation
This webinar introduces case studies and highlights best practices used to overcome crystallization and precipitation challenges. The focus will be on...

Citations

Crystallization and Precipitation Citation List
Crystallization and precipitation citation list and publications

Produkty pokrewne

Crystallization Metastable Zone Width (MSZW)