Quantification of secondary nucleation kinetics can be performed at various conditions: 1. This feature clearly makes it very attractive to implement this technique in a continuous crystallization process. Although MSMPR conditions often do not hold, the model is useful and helps understanding of continuous crystallization processes in agitated vessels. Statement 2: Used in isolation of organic compounds. The method with which a supersaturated solution with S > 1 is created in a crystallizer defines the crystallization method used. With rapid mixing there is the issue of what happens to the seed suspension immediately after it is created. The critical mixing factors have been identified as impeller type and speed and their influence on local turbulence and overall circulation. Attrition causes small particles of acetaminophen crystals that have already been formed on the surface of the excipient to break and enter the solution, thus causing secondary nucleation (acting as seeds). In this respect an understanding of the effect of solution conditions on macromolecule nucleation rates is advantageous. The differences in operating windows for the different subprocesses in crystallization and the need for specific conditions for local nucleation have been framed before.109. What is the role of buffer pH and salt conc. in crystallization? The capability to manipulate CST is dominated by the ability to manipulate the secondary nucleation rate and allow the system to readjust to a new steady state through growth. In the work which uses glass channels, continuous seed generation was performed by firstly cooling the clear solution inside a length of tubing to generate supersaturation before exposing this solution to ultrasound inside the glass channel by means of an ultrasonic transducer.128,129 These studies show that the mean particle size can be controlled with both supersaturation and ultrasonic power, with increasing supersaturation and ultrasonic power leading to a smaller mean particle size. Consequently, adding a small particle of the solute, a seed crystal, will usually cause the excess solute to rapidly precipitate or crystallize, sometimes with spectacular results. If, for instance, the secondary nucleation rate due to attrition with the stirrer is the dominant nucleation mechanism, the stirrer speed influences the attrition. In order to achieve turbulent rather than laminar flow conditions in a simple long straight tube, the flow rate would need to be very large, resulting in small residence times. Part 1: Free Energy of Binding to a Binding Site, Surface Design for Controlled Crystallization: The Role of Surface Chemistry and Nanoscale Pores in Heterogeneous Nucleation, Continuous Heterogeneous Crystallization and the New Method of Making Tablets, In-situ monitoring and characterization of plug flow crystallizers, Continuous crystallization using a sonicated tubular system for controlling particle size in an API manufacturing process, Reaction crystallization kinetics of benzoic add, Kinetics identification of salicylic acid precipitation through experiments in a batch stirred vessel and a T-mixer, Observation of Single Colloidal Platinum Nanocrystal Growth Trajectories, Mechanisms of Nucleation and Growth of Nanoparticles in Solution, Solidification behavior of highly supercooled polycrystalline silicon droplets, Understanding temperature-induced primary nucleation in dual impinging jet mixers, Engineering of acetaminophen particle attributes using a wet milling crystallisation platform, Modeling and Characterization of an in Situ Wet Mill Operation, Modeling-Aided Scale-Up of High-Shear RotorStator Wet Milling for Pharmaceutical Applications, The stability of nuclei generated by contact nucleation, Contact nucleation of various crystal types, Reducing the Induction Time Using Ultrasound and High-Shear Mixing in a Continuous Crystallization Process, The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities, Influence of Ultrasound on the Nucleation of Polymorphs of p-Aminobenzoic Acid, Ultrasound Assisted Crystallization of Paracetamol: Crystal Size Distribution and Polymorph Control, Application of generic principles of process intensification to solution crystallization enabled by a task-based design approach, Kinetic identification and experimental validation of continuous plug flow crystallisation, Controlled liquid antisolvent precipitation using a rapid mixing device, Continuous Precipitation of L-Asparagine Monohydrate in a Micromixer: Estimation of Nucleation and Growth Kinetics, Seeded Crystallization of beta-L-Glutamic Acid in a Continuous Oscillatory Baffled Crystallizer, Crystallization Diagram for Antisolvent Crystallization of Lactose: Using Design of Experiments To Investigate Continuous Mixing-Induced Supersaturation, Continuous Cocrystallization of Benzoic Acid and Isonicotinamide by Mixing-Induced Supersaturation: Exploring Opportunities between Reactive and Antisolvent Crystallization Concepts, Continuous Plug Flow Crystallization of Pharmaceutical Compounds, Design of a Continuous Tubular Cooling Crystallizer for Process Development on Lab-Scale, Characterization and modelling of antisolvent crystallization of salicylic acid in a continuous oscillatory baffled crystallizer, Process Intensification through Continuous Spherical Crystallization Using an Oscillatory Flow Baffled Crystallizer, Effect of operating conditions on batch and continuous paracetamol crystallization in an oscillatory flow mesoreactor, Continuous Sonocrystallization of Acetylsalicylic Acid (ASA): Control of Crystal Size, Indirect Ultrasonication in Continuous Slug-Flow Crystallization, Continuous-Flow Sonocrystallization in Droplet-Based Microfluidics, Investigation of the Effect of Ultrasound Parameters on Continuous Sonocrystallization in a Millifluidic Device, Ultrasound Assisted Particle Size Control by Continuous Seed Generation and Batch Growth, Establishment of a Continuous Sonocrystallization Process for Lactose in an Oscillatory Baffled Crystallizer, Process Intensification through Continuous Spherical Crystallization Using a Two-Stage Mixed Suspension Mixed Product Removal (MSMPR) System, Development of Continuous Crystallization Processes Using a Single-Stage Mixed-Suspension, Mixed-Product Removal Crystallizer with Recycle, Development of Continuous Anti-Solvent/Cooling Crystallization Process using Cascaded Mixed Suspension, Mixed Product Removal Crystallizers, Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays, Continuous Crystallization of Aliskiren Hemifumarate, Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer, Continuous Crystallization of Cyclosporine: Effect of Operating Conditions on Yield and Purity, Continuous crystallization of adipic acid with ultrasound, Monitoring Continuous Crystallization of Paracetamol in the Presence of an Additive Using an Integrated PAT Array and Multivariate Methods, Automated Direct Nucleation Control in Continuous Mixed Suspension Mixed Product Removal Cooling Crystallization, Influence of feeding mode on cooling crystallization of L-lysine in Couette-Taylor crystallizer, Characterization of the anti-solvent batch, plug flow and MSMPR crystallization of benzoic acid, Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit, Estimation of Nucleation and Growth Kinetics of Benzoic Acid by Population Balance Modeling of a Continuous Cooling Mixed Suspension, Mixed Product Removal Crystallizer, Design and optimization of a multistage continuous cooling mixed suspension, mixed product removal crystallizer, Integrated Upstream and Downstream Application of Wet Milling with Continuous Mixed Suspension Mixed Product Removal Crystallization, Application of Wet Milling-Based Automated Direct Nucleation Control in Continuous Cooling Crystallization Processes, Statistical Design of Experiment on Contact Secondary Nucleation as a Means of Creating Seed Crystals for Continuous Tubular Crystallizers. The crystallizer suspension has a temperature and concentration lower than those of the feed. 1.10. Key Factors for Successful Protein Purification and Crystallization As with the standard MSMPR cascade, the upstream wet mill feeding to an MSMPR can be combined with a nucleation control strategy where particle chord count information from the FBRM is used to implement heating or cooling rates to maintain particle chord counts in a desired setpoint range during the crystallization process.148 This additional control in the MSMPR allows for the PSD to be more finely tuned. Thus, while an unseeded batch cooling crystallization process usually relies on primary nucleation to provide the crystals, during a continuous crystallization process the omnipresent crystals continuously generate more crystals through secondary nucleation. Few proteins will be soluble and stable in the absence of NaCl or a similar ionic compound and you will have to test how low you can drive its concentration before the protein crashes out of. Inserting an ultrasound probe in a OBC demonstrated that ultrasound assisted continuous seed generation could be implemented reliably at a larger scale.130 It was shown that using sonication allowed for the mean particle size to be controlled with a narrower PSD than in the equivalent batch process. OBCs have the advantage over standard tubular devices that they provide good mass and heat transfer even at low flow rates due to the fluid oscillation. Of the common silicate minerals, olivine normally crystallizes first, at between 1200 and 1300C. In a continuous cooling crystallization for instance the hot solution feed at temperature with concentration and flow rate enters the crystallizer and is mixed up with a suspension which has a specific steady state solution concentration and suspension density of crystals in the solution at temperature. These can be seen as mechanical separation of preformed crystals (or their pieces) from larger crystals or aggregates/agglomerates, typically due to collisions with impellers, vessel walls or with other crystals or due to fluid action on crystal (e.g., fluid shear or turbulent eddies). (December 2013) Crystals of proteins grown on the U.S. Space Shuttle or Russian Space Station, Mir.
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