Crystallisation & Precipitation - Basics, Definitions & Common Parameters
Crystallization and Precipitation

Crystallisation and Precipitation

Optimize Crystal Size, Yield and Purity

What is Crystallization?

Types of Crystallization
Crystallization Challenges
Design a Crystallization Process
Crystallization Cooling Rates

Applications

Application Guide to Crystallization Development and Scale-up

Solubility and 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.

Crystal Nucleation and Growth
The Driving Force For Crystal Nucleation and Growth

Scientists and engineers gain control of crystallization processes by carefully adjusting the level of supersaturation during the process. Supersaturation is the driving force for crystallization nucleation and growth and will ultimately dictate the final crystal size distribution.

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.

Particle Engineering and Wet Milling
Control Particle Size With High Shear Wet Milling

Milling of dry powders can cause significant yield losses and can generate dust, creating health and safety hazards. In response to this, wet milling produces particles with a specifically designed size distribution. It is now common to employ high shear wet milling to break large primary crystals and agglomerates into fine particles.

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.

Chemical Process Development & Scale-Up
Design Robust and Sustainable Chemical Processes For Faster Transfer To Pilot Plant and Production

Design Robust and Sustainable Chemical Processes For Faster Transfer To Pilot Plant and Production

Chemical Reaction Kinetics Studies
Study Chemical Reaction Rates and Measure Kinetics Inline

In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data.  Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.

Solubility and 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.

Crystal Nucleation and Growth

Scientists and engineers gain control of crystallization processes by carefully adjusting the level of supersaturation during the process. Supersaturation is the driving force for crystallization nucleation and growth and will ultimately dictate the final crystal size distribution.

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.

Particle Engineering and Wet Milling

Milling of dry powders can cause significant yield losses and can generate dust, creating health and safety hazards. In response to this, wet milling produces particles with a specifically designed size distribution. It is now common to employ high shear wet milling to break large primary crystals and agglomerates into fine particles.

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.

Chemical Process Development & Scale-Up

Design Robust and Sustainable Chemical Processes For Faster Transfer To Pilot Plant and Production

Chemical Reaction Kinetics Studies

In situ chemical reaction kinetics studies provide an improved understanding of reaction mechanism and pathway by providing concentration dependences of reacting components in real-time. Continuous data over the course of a reaction allows for the calculation of rate laws with fewer experiments due to the comprehensive nature of the data.  Reaction Progression Kinetics Analysis (RPKA) uses in situ data under synthetically relevant concentrations and captures information throughout the whole experiment ensuring that the complete reaction behavior can be accurately described.

Publications

Crystallization and Precipitation Engineering Case Studies

White Papers

How to Optimize a Crystallization Step Using Simple Image Analysis
By quickly identifying unnecessary hold times and determining how cooling rate influences crystal growth and nucleation, the cycle time for an interme...
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...
Effective Crystallization Process Development
The quality of a crystallization process greatly influences the quality of the final product. Our new white paper introduces you to the fundamentals o...
Strategies To Control Crystal Size Distribution
This white paper discusses strategies to optimize crystal size distribution during process development and manufacturing.
Improve Industrial Crystallization
Industrial crystallization is an important separation and purification step in the chemical industry. A white paper shows how inline particle technol...
Seeding a 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
Real-time monitoring of crystallization is shown to provide benefits leading to improved methods for process development, optimization and scale-up. T...
Best Practices For Crystallization Development
This white paper demonstrates the methodology chemists use to optimize critical crystallization parameters such as: Temperature profile Addition rates...
Best Practice For Inline Particle Size Characterization
Apply inline particle size and count characterization to measure fines precipitation to improve solid/liquid separations, improve product stability du...

Citations

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

Webinars

Designing Continuous Crystallization Platforms
This webinar describes an investigation into the characterization, design and operation of continuous crystallization. Robust crystallization process...
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...
Crystallization Image Analysis
This presentation describes the role of image analysis in crystallization monitoring.
Liquid-Liquid Phase Separation
This presentation describes a strategy employed to design and develop robust, scalable crystallization processes that avoids Liquid-Liquid Phase Separ...
Agglomeration & Crystallization Using Particle Measurement
This presentation details how using data from in situ particle vision and measurement tools can be used to determine particle size and shape trends re...
Crystallization Scale-up Strategy Development
During this webinar, two case studies are presented to illustrate the application of tools and strategies that were utilized to understand and manage...
Wet Milling Impact on Particle Size
This presentation details the development, understanding, and scale-up of an aseptic crystallization, which utilizes a novel wet milling during anti-s...
Pharmaceutical Drug Substance Crystallization
This presentation describes the case of crystals of an Active Pharmaceutical Ingredient (API) with high propensity to float in their mother liquors, d...

Application Notes

In-Process Characterization of Antisolvent Crystallization
Ensure fast and efficient scale-up by optimizing crystallization early in development. Target particle size specifications to speed up downstream proc...
Polymorph and Pseudo-polymorph Transition in-process monitoring of habit change
Improve purity by ensuring total polymorphic form conversion. Enhance process robustness by monitoring crystallization processes in real time. Charact...

Related Products

Technology for Crystallization Development and Scale-up

 
 
 
 
 
 
 
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