Kristallisatie en neerslag - basiskennis, definities en gemeenschappelijke parameters

Kristallisatie en neerslag

Optimaliseer de grootte, opbrengst en zuiverheid van kristallen

Wat is kristallisatie?
Kristallisatie en neerslag

Soorten kristallisaties
Kristallisatie uitdagingen
Een kristallisatieproces ontwikkelen
Afkoelsnelheid van de kristallisatie

Applicaties

Toepassingsgids voor ontwikkeling van kristallisaties en opschaling

Polymorphism Identification and Control
Understand Polymorphism and the Impact of Process Parameters

Polymorphism is a common phenomenon with many crystalline solids in the pharmaceutical and fine chemical industry. Scientists deliberately crystallize a desired polymorph to improve isolation properties, help overcome downstream process challenges, increase bioavailability or to prevent patent conflicts. Identifying polymorphic and morphological transformations in-situ and in real time eliminates unexpected process upset, out of specification product and costly reprocessing of material.

Optimalisatie van kristaleigenschappen en procesprestaties

Wetenschappers herkristalliseren hoogwaardige chemische stoffen om een kristalproduct te verkrijgen met de gewenste fysieke eigenschappen bij een optimale procesefficiëntie. Het ideale herkristallisatieproces bestaat uit zeven stappen, van de selectie van het juiste oplosmiddel tot het verkrijgen van een droog kristalproduct. Deze herkristallisatiegids legt stapsgewijs de procedure uit voor de ontwikkeling van een herkristallisatieproces. In de gids wordt uitgelegd welke informatie tijdens elke herkristallisatiefase nodig is en hoe de kritieke procesparameters worden aangestuurd.

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.

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.

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.

Procesontwikkeling en opschaling
Robuust ontwerp en duurzame chemische processen

Ontwikkel degelijke en duurzame chemische processen om de overdracht naar de pilot plant en productie te bespoedigen

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.

Polymorphism Identification and Control

Polymorphism is a common phenomenon with many crystalline solids in the pharmaceutical and fine chemical industry. Scientists deliberately crystallize a desired polymorph to improve isolation properties, help overcome downstream process challenges, increase bioavailability or to prevent patent conflicts. Identifying polymorphic and morphological transformations in-situ and in real time eliminates unexpected process upset, out of specification product and costly reprocessing of material.

Wetenschappers herkristalliseren hoogwaardige chemische stoffen om een kristalproduct te verkrijgen met de gewenste fysieke eigenschappen bij een optimale procesefficiëntie. Het ideale herkristallisatieproces bestaat uit zeven stappen, van de selectie van het juiste oplosmiddel tot het verkrijgen van een droog kristalproduct. Deze herkristallisatiegids legt stapsgewijs de procedure uit voor de ontwikkeling van een herkristallisatieproces. In de gids wordt uitgelegd welke informatie tijdens elke herkristallisatiefase nodig is en hoe de kritieke procesparameters worden aangestuurd.

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.

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.

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.

Procesontwikkeling en opschaling

Ontwikkel degelijke en duurzame chemische processen om de overdracht naar de pilot plant en productie te bespoedigen

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.

Publicaties

Technische case-study's over kristallisaties en neerslag hiervan

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...
Verbeteren van industriële kristallisatie
Industriële kristallisatie is een belangrijke stap van scheiding en zuivering in de chemische industrie. Een white paper geeft aan hoe inline deeltjes...
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...
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 Size Analysis for Process Optimization
This white paper introduces some of the most common particle size analysis approaches and how they can be deployed for the effective delivery of high...

Literatuurverwijzingen

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

Webinars

Platforms voor continue kristallisatie ontwerpen
Deze webinar beschrijft het onderzoek naar de karakterisering, het ontwerp en de werking van continue kristallisatie. Er worden robuuste kristallisati...
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...
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

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...

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Technologie voor ontwikkeling van kristallisaties en opschaling

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