Kinetics of Crystallization in Supersaturation

Supersaturation Control Optimizes Crystal Size and Shape

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Guide to Crystallization Development
Supersaturation Profiling
Non-Linear Cooling Rates for Constant Supersaturation
Automated Supersaturation Control
Particle Size Analysis for Process Optimization

Applications

Applications For Understanding Crystallization Kinetics

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.

Crystallization Seeding Protocol
Design and Optimize Seeding Protocol for Improved Batch Consistency

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.

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.

Crystal Polymorphism
Understand Polymorphism and the Impact of Process Parameters

Crystal polymorphism describes the ability of one chemical compound to crystallize in multiple unit cell configurations, which often show different physical properties.

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.

Batch Crystallization Optimization and Process Design
Generate Supersaturation and Determine Final Crystal Product

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 Processes
Real-Time Monitoring for Modeling and Control

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.

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.

Crystallization Seeding Protocol

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.

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.

Crystal Polymorphism

Crystal polymorphism describes the ability of one chemical compound to crystallize in multiple unit cell configurations, which often show different physical properties.

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.

Batch Crystallization Optimization and Process Design

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 Processes

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.

Publications

Publications on Crystallization Kinetics

White Papers

Understand Crystallization with In-Situ Microscopy
Dynamic mechanisms key to understanding crystallization processes can now be observed with in-situ microscopy. A white paper explains how leading chem...
Crystallization Process pdf
This white paper introduces you to the fundamentals of crystallization process development and provides guidance for the design of a high quality crys...
crystal size distribution ppt
This white paper discusses strategies to optimize crystal size distribution during process development and manufacturing.
industrial crystallization white paper
Optimization of the industrial crystallization process leads to increased yield and purity, reduced energy consumption and cost, and improved product...
seeding crystallization process
Seeding is a key step in optimizing a crystallization process, ensuring a consistent filtration rate, yield, polymorphic form and particle size distri...
Scale-up of Batch Crystallization From Lab to Plant
Scale-up of crystallization is notoriously complicated and companies are under pressure to develop scalable crystallization processes faster - at lowe...
Best Practices for Crystallization Development
This white paper demonstrates the methodology chemists use to optimize critical crystallization parameters such as temperature profile, addition rates...
Particle Characterization From Small Scale Lab Reactors to Full Scale Production Pipelines
Particle size analysis approaches are deployed for effective delivery of high quality particle products. Combining offline particle size analyzers wi...

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

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