Crystallization and Precipitation

    Crystallization and Precipitation

    Optimize Crystal Size, Yield and Purity

    Applications

    Application Guide to Crystallization Development and Scale-up

    Introducing Crystallization and Precipitation
    Optimize Crystal Size, Yield and Purity

    Crystallization is an important process in the chemical, petrochemical and pharmaceutical industries. Guidelines for engineering challenging unit operations can improve final product quality, downstream filtration and drying performance.

    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 anti-solvent 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 anti-solvent addition protocol and the level of supersaturation.

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

    The cooling profile has a major impact on supersaturation and kinetics of crystallization Process temperature is optimized to match the surface are of crystals for optimal growth versus nucleation. 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 anti-solvent 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.

    Introducing Crystallization and Precipitation

    Crystallization is an important process in the chemical, petrochemical and pharmaceutical industries. Guidelines for engineering challenging unit operations can improve final product quality, downstream filtration and drying performance.

    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 anti-solvent 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 anti-solvent addition protocol and the level of supersaturation.

    Temperature Effects Crystallization Size and Shape

    The cooling profile has a major impact on supersaturation and kinetics of crystallization Process temperature is optimized to match the surface are of crystals for optimal growth versus nucleation. 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 anti-solvent 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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