Predicting and Optimizing Filtration and Drying Cycle Time

Optimizing For Downstream Process Efficiency Involves Avoiding Bottlenecks and Improving Cycle Time

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Crystallized product is often separated from the mother liquor by methods of filtration or centrifugation, followed by drying. A wide crystal size distribution with a significant numbers of “fines” often results in poor filterability which can add hours or even days to process cycle time. Poor filterability also relates directly to mother liquor retention which impacts crystal product purity – requiring additional washes with hot solvent which can further increase cycle time and reduce yields.

FBRM process analytical tools are widely used for real-time monitoring and optimization of crystallization for the purpose of avoiding downstream bottlenecks due to poor filterability of the crystal product.

Predicting and Optimizing Filtration and Drying Cycle Time
Predicting and Optimizing Filtration and Drying Cycle Time

Applicaties

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.

Herkristallisatie uitleg en stappen
Optimalisatie van kristaleigenschappen en procesprestaties

Herkristallisatie zorgt voor kristalproducten met de gewenste fysieke eigenschappen. Hier vindt u alle informatie ende zeven stappen van het ideale herkristallisatieproces.

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.

Kristalnucleatie en -groei
De drijvende kracht voor kristalnucleatie en -groei

Wetenschappers en technici kunnen kristallisatieprocessen beheersen door het niveau van oververzadiging tijdens het proces zorgvuldig aan te passen. Oververzadiging is de drijvende kracht voor kristalnucleatie en -groei en bepaalt de uiteindelijke verdeling van de kristalgrootte.

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.

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.

MSMPR crystallizer workstation
Improve Crystallization Experiments with Precise Control

The MSMPR (Mixed Suspension Mixed Product Removal) crystallizer is a type of crystallizer used in industrial processes to produce high-purity crystals.

Crystal Polymorphism

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

Herkristallisatie uitleg en stappen

Herkristallisatie zorgt voor kristalproducten met de gewenste fysieke eigenschappen. Hier vindt u alle informatie ende zeven stappen van het ideale herkristallisatieproces.

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.

Kristalnucleatie en -groei

Wetenschappers en technici kunnen kristallisatieprocessen beheersen door het niveau van oververzadiging tijdens het proces zorgvuldig aan te passen. Oververzadiging is de drijvende kracht voor kristalnucleatie en -groei en bepaalt de uiteindelijke verdeling van de kristalgrootte.

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.

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.

MSMPR crystallizer workstation

The MSMPR (Mixed Suspension Mixed Product Removal) crystallizer is a type of crystallizer used in industrial processes to produce high-purity crystals.

Publicaties

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...
Begrijp kristallisatie met in situ microscopie
Dynamische mechanismes zijn de sleutel voor het begrijpen van kristallisatieprocessen en kunnen nu geobserveerd worden met in situ microscopie. Een wh...
effectieve kristallisatie procesontwikkeling
De kwaliteit van een kristallisatieproces is van grote invloed op de kwaliteit van het eindproduct. Met onze nieuwe white paper kunt u kennismaken met...
Strategieën om de kristalgrootteverdeling te controleren
Farmaceutische en hoogwaardige chemicaliën moeten vaak tijdens ontwikkeling en productie meerdere kristallisatiestappen doorlopen. Een nieuwe white pa...
Strategieën om de kristalgrootteverdeling te controleren
Farmaceutische en hoogwaardige chemicaliën moeten vaak tijdens ontwikkeling en productie meerdere kristallisatiestappen doorlopen. Een nieuwe white pa...
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...
Opschaling van batchkristallisatie van lab naar productie
Real-time controle van kristallisatie levert voordelen die zorgen voor betere methodes voor procesontwikkeling, optimalisatie en opschaling.
'Best practice' voor kristallisatie-ontwikkeling
Dit white paper behandelt de methodologie die door scheikundigen wordt gebruikt om kritieke kristallisatieparameters te optimaliseren, zoals:
Particle Characterization From Small Scale Lab Reactors to Full Scale Production Pipelines
Particle Characterization From Small Scale Lab Reactors to Full Scale Production Pipelines Door offline particle size analyzers met in-proces instrum...

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...
Eliminatie van micronisatie met kristallisatie van fijne deeltjes
Kristalengineering wordt gebruikt wanneer de distributie van de kristalmaat te groot is om aan de downstream specificaties te voldoen. Door ervoor te...
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...

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