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.
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. 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. Liquid-Liquid phase separation, or oiling out, is an often difficult to detect particle mechanism that can occur during crystallization processes.
Learn more. 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. 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. 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. 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 and Scale-Up guides the development of a commercially important molecule from synthesis in the lab to large scale manufacture of a quality product.
Chemical reaction kinetics, also known as reaction kinetics, reflect rates of chemical reactions and provide a better understanding of their dependencies on reaction variables. Reaction kinetic studies provide enhanced insight into reaction mechanisms.
Learn how to obtain data rich information for more complete reaction kinetic information. Polymorphism chemistry is a common phenomenon with many crystalline solids in the pharmaceutical and fine chemical industries. 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.
Protein crystallization is the act and method of creating structured, ordered lattices for often-complex macromolecules. Lactose crystallization is an industrial practice to separate lactose from whey solutions via controlled crystallization. Automated Reactors and In Situ Analysis. Transport and Logistics. Expertise Library. Literature: White Papers, Guides, Brochures. Technical Documentation. On Demand Webinars. Live Events. Live Webinars. Management Investor Relations.
Service Finder Videos. Select Country. What Is Crystallization? Why is Crystallization Important? Key Crystallization Definitions Crystallization Crystallization is a process whereby solid crystals are formed from another phase, typically a liquid solution or melt. Solubility Solubility is a measure of the amount of solute that can be dissolved in a given solvent at a given temperature Saturated Solution At a given temperature, there is a maximum amount of solute that can be dissolved in the solvent.
Types of Crystallization Methods To Induce Crystallization Crystallization occurs when the solubility of a solute in solution is reduced by some means.
Common methods to reduce solubility include: a. Cooling b. Antisolvent Addition c. Evaporation of Solvent d. Precipitation Through Chemical Reaction The choice of crystallization method depends on the equipment available for crystallization, the objectives of the crystallization process and the solubility and stability of the solute in the chosen solvent.
Crystallization Steps Choose an appropriate solvent. Common considerations included how much solute can be dissolved solubility and how practical the solvent is to handle safety Dissolve the product in the solvent by increasing the temperature until all solids of the product are dissolved.
At this moment, insoluble impurities may be filtered from the hot solution Reduce solubility via cooling, anti-solvent addition, evaporation or reaction. The solution will become supersaturated. Crystallize the product. As solubility is reduced, a point is reached where crystals will nucleate and then grow.
Highly pure product crystals should form and impurities should remain in solution. Allow the system to reach equilibrium to maximize the yield of product solid. Filter and dry the purified product. Common Crystallization Challenges Crystallization proceeds through a series of interdependent mechanisms that are each uniquely influenced by the choice of process parameters: Nucleation Growth Oiling Out in Crystallization Agglomeration Breakage Polymorphism Chemistry These mechanisms, which are often hidden form scientists, play a dominant role in defining the outcome of a crystallization process.
Get the Guide to Crystallization Mechanisms. Case Study: Crystallization Cooling Rates In this example, the cooling rate at the end of the batch induces secondary nucleation resulting in the formation of many fine particles - using particle size analyzers. Crystallization Equipment Process Analytical Technology for Crystallization Engineering A crystallization workstation allows scientists to obtain maximum scientific information from a single experiment in a centralized software suite.
Automated Reactors Precise Control of Critical Process Parameters Process parameters like temperature, stirring and dosing rate have a direct impact on the product and process quality of particle systems. Particle Characterization Measure Particles as they Naturally Exist in Process Particle size, shape and concentration are critical pieces of information at every stage or scale during a crystallization process and hence make Critical Quality Attributes CQA.
Particle properties and particle mechanisms are recorded for review and analysis at all times, even if scientists cannot be in the lab Interoperability between Automated Reactors and ParticleTrack and EasyViewer enable scientists to set up Feedback Control Loops for particle size or count controlled cooling, or antisolvent dosing rates to minimize undesired particle populations, such as excessive fines The intuitive "Start Experiment Wizard" makes it easy for every scientists to quickly collect high-quality particle data.
In order for crystallization to take place a solution must be "supersaturated". Supersaturation refers to a state in which the liquid solvent contains more dissolved solids solute than can ordinarily be accomodated at that temperature.
So how do you grow crystals? Let's consider an example that is fairly easy to envision. Take a pot of boiling water and add table salt while stirring to make a water-salt solution. Continue adding salt until no more salt will dissolve in the solution this is a saturated solution. Now add one final teaspoon of salt. The salt that will not dissolve will help the first step in crystallization begin. This first step is called "nucleation" or primary nucleation.
The salt resting at the bottom of the pot will provide a site for nucleation to occur. Primary nucleation is the first step in crystallization. Simply defined, it's the growth of a new crystal. On an industrial scale, a large supersaturation driving force is necessary to initiate primary nucleation. The collapse of the bubble provides energy to encourage the nucleation process at the earliest possible point in time.
This results in highly repeatable and predictable crystallizations, and offer various benefits, including;. Discover the Sonocrystallization application page for more information.
Having decided on a method of crystallization, it is important to measure the progress and subsequent success of your crystallization process.
Turbidity probes have been used to monitor crystallizations for decades, due to their ease of use, sensitivity, and affordability. Turbidity probes work by measuring light that is scattered by suspended solids in a liquid. As an example, turbidity information for the crystallization and dissolution of adipic acid is shown below:. FBRM probes work by directing a laser beam down the probe, through rotating optics and focussing it at the probe window and measuring the light backscattered by particles in solution.
As the focussed beam scans the solution, individual particles can backscatter the light to the detector. Video imaging probes have also been used determine crystal shape and crystal size distribution, however, at present, they are hard to implement at a commercial scale due to operating temperature limits and the bulky size of such probes. Attenuated total reflectance Fourier transform infrared ATR-FTIR has also been used to gather solubility and supersaturation data, by measuring the concentration of solute in the mother liquor.
Additional information can also be gleaned, such as confirmation of the presence of additives or impurities. Chemists have a range of tools available to them for performing, monitoring, and controlling crystallization chemistry. Syrris systems offer a range of solutions to the problem of crystallization monitoring and control. Atlas HD Crystallization is an intelligent and automated jacketed reactor system that offers a turbidity probe for monitoring the crystallization process, and the innovative SonoLab module to perform sonocrystallization or sonomilling techniques.
Using the Syrris Atlas HD Crystallization system for your crystallization studies offers various benefits, including;. Syrris products offer a range of solutions to the problem of crystallization control and monitoring. For more information about crystallization or how you can achieve better results using Syrris products, please contact us.
What is crystallization? How does the crystallization process occur? The crystallization process consists of two major events: Nucleation — Molecules gather together in clusters in a defined manner. It is this point in the crystallization process that defines the crystal structure. Crystal growth is a dynamic process, with atoms precipitating from solution and becoming redissolved. Supersaturation and supercooling are two of the most common driving forces behind crystal formation.
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