Mixed Product Removal Research Articles

Effect of calcium based additives on the sodium bicarbonate crystallization in a MSMPR reactor

The objective of this work was to study the impact of calcium ions addition on the crystallization of sodium bicarbonate during the reaction of sodium carbonate with carbon dioxide in aqueous solutions. A continuous MSMPR (Mixed Suspension Mixed Product Removal) reactor for the production of sodium bicarbonate was developed, built and tested at pilot scale. This experimental set-up was used to study the impact of process parameters and the effect of calcium based additives on the quality of the NaHCO3 crystals obtained. The nucleation and crystal growth rates were determined from the experimental population density distribution when the steady state was reached. Experiments have firstly shown that the addition of calcium ions greatly reduced the nucleation rate. In contrast, the addition of calcium ions had little impact on crystal growth rate in the temperature range between 70°C and 80°C.

Synthesis of Uniformly Spherical Bayerite from a Sodium Aluminate Solution Reacted with Sodium Bicarbonate

Bayerite was synthesized successfully by the precipitation reaction of a sodium aluminate solution with sodium bicarbonate in a mixed suspension–mixed product removal (MSMPR) crystallizer. The particle size distribution of the prepared bayerite was significantly influenced by the temperature, the stirring speed, and the molar ratio (MR) of Na2Oc/Na2Ok as well as the addition rate of aqueous NaHCO3 solution in the system. The uniformly spherical bayerite with narrow “missing-fines-type” particle size distribution was obtained at 50 °C, with the MR of 0.66, at the agitation speed of 300 rpm in the MSMPR crystallizer. The synthesis of bayerite from the reactive NaAl(OH)4–NaHCO3 system was without an aging process. The thermal decomposition of the prepared bayerite was analyzed by TGA/DSC and XRD.

Study of neodymium oxalate precipitation in a continuous mixed suspension mixed product removal

Study of Neodymium Oxalate Precipitation in a Continuous Mixed Suspension Mixed Product Removal Jean-Philippe Gaillard, Murielle Bertrand, Sophie Lalleman, Olivier Lebaigue, Edouard Plasari CEA, Nuclear Energy Division, RadioChemistry & Process Department, French Alternatives Energies and Atomic Energy Commission, F-30207 Bagnols sur Ceze, France CEA, Nuclear Energy Division, Reactor Studies Department, French Alternatives Energies and Atomic Energy Commission, F-38054 Grenoble, France Laboratoire Reactions et Genie des Procedes, Universite de Lorraine, 1 rue Granville BP 20451, 54001 Nancy,France jean-philippe.gaillard@cea.fr

Contact Secondary Nucleation as a Means of Creating Seeds for Continuous Tubular Crystallizers

The control of crystal size of any crystallization process is especially important in the pharmaceutical industry where small sizes are often desired. Seeding is often used as a method of controlling crystal size and suppressing primary nucleation in batch processes. The continuous mixed suspension mixed product removal crystallizers are self-seeded; however, crystal attrition and contact secondary nucleation due to crystal interaction with the impeller influence the crystal size. In this study, a nuclei generation device (nucleator) employing contact secondary nucleation is described. The nucleator consists of a “crossed” flow tube with four openings. Two of the openings are the inlet of supersaturated solution and the outlet of crystal slurry, respectively. The other two openings are for contact nucleation, where the parent crystal comes into contact with a platform under an applied stress. The rate of nucleation and the size of the crystals generated can be controlled by supersaturation (S = c/cs) and ...

Preparation and crystallization kinetics of micron-sized Mg(OH)2 in a mixed suspension mixed product removal crystallizer

Magnesium hydroxide is an important chemical, and is usually obtained from seawater or brine via precipitation process. The particle size distribution of magnesium hydroxide has great effects on the subsequent filtration and drying processes. In this paper, micron-sized magnesium hydroxide with high purity, large particle size and low water content in filter cake was synthesized via simple wet precipitation in a mixed suspension mixed product removal (MSMPR) crystallizer. The effects of reactant concentration, residence time and impurities on the properties of magnesium hydroxide were investigated by X-Ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Malvern laser particle size analyzer. The results show that NaOH concentration and residence time have great effects on the water content and particle size of Mg(OH)2. The spherical Mg(OH)2 with uniform diameter of about 30 μm was obtained with purity higher than 99% and water content less than 31%. Furthermore, the crystallization kinetics based on the population balance theory was studied to provide the theoretical data for industrial enlargement, and the simulation coefficients (R2) based on ASL model and C-R model are 0.9962 and 0.9972, respectively, indicating that the crystal growth rate of magnesium hydroxide can be well simulated by the sizedependent growth models.

Phosphates (V) recovery from phosphorus mineral fertilizers industry wastewater by continuous struvite reaction crystallization process

Continuous DT MSMPR (Draft Tube Mixed Suspension Mixed Product Removal) crystallizer was provided with typical wastewater from phosphorus mineral fertilizers industry (pH < 4, 0.445 mass % of PO43−, inorganic impurities presence), dissolved substrates (magnesium and ammonium chlorides) and solution alkalising the environment of struvite MgNH4PO4·6H2O reaction crystallization process. Research ran in constant temperature 298 K assuming stoichiometric proportions of substrates or 20% excess of magnesium ions. Influence of pH (8.5–10) and mean residence time (900–3600 s) on product size distribution, its chemical composition, crystals shape, size–homogeneity and process kinetics was identified. Crystals of mean size ca. 25–37 μm and homogeneity CV 70–83% were produced. The largest crystals, of acceptable homogeneity, were produced using 20% excess of magnesium ions, pH 9 and mean residence time 3600 s. Under these conditions nucleation rate did not exceed 9 × 107 1/(s m3) according to SIG (Size Independent Growth) MSMPR kinetic model. Linear crystal growth rate was 4.27 × 10−9 m/s. Excess of magnesium ions influenced struvite reaction crystallization process yield advantageously. Concentration of phosphate(V) ions decreased from 0.445 to 9.2 × 10−4 mass %. This can be regarded as a very good process result. In product crystals, besides main component – struvite, all impurities from wastewater were detected analytically.

Material size distribution in concurrent bio-leaching and precipitation: Experimental procedure and modelling

This study presents the approach used to develop a model for a continuous bioleaching system in stirred tank reactors. In bioleaching of metallic sulfides, precipitation concurrently occurs with dissolution of sulfides. Therefore, the model incorporates both the leaching and the precipitation kinetics. It is based on a shrinking particle model for the leaching part and a Mixed Suspension Mixed Product Removal (MSMPR) crystallizer model with germination and growing kinetics for the precipitation part.To establish the model, it was necessary to have access to the size distribution of both sulfide and precipitated particles. A procedure for the bioleached residue characterization was developed in the BRGM laboratory to be able to dissociate sulfide and precipitated particles in the solid phase.The current paper presents the analytical procedure, the mathematical model in detail and its application to a continuous pilot plant test.

Development of Continuous Crystallization Processes Using a Single-Stage Mixed-Suspension, Mixed-Product Removal Crystallizer with Recycle

An ideal pharmaceutical crystallization process produces a pure product at a high yield while minimizing energy input, the process equipment footprint, and its complexity. A good candidate for such a process is a single-stage mixed-suspension, mixed-product removal (MSMPR) crystallizer with recycle (SMR) system, where the characteristics of the refined crystal are controlled by the crystallization conditions of the MSMPR and the yield is manipulated by the recycle ratio. In this study, two continuous SMR systems, for the cooling crystallization of cyclosporine and the antisolvent-cooling crystallization of deferasirox, were developed. Both systems were designed to maintain the desired operating conditions inside the MSMPR crystallizer. For cooling crystallization, the recycle stream was concentrated via vacuum evaporation. For antisolvent-cooling crystallization, the desired solvent to antisolvent ratio was maintained by controlling the flow rates of feed, antisolvent, and recycle streams. The maximum exp...

FREQUENCY DOMAIN MODEL SIMPLIFICATION OF CUMULATIVE MASS FRACTION IN CMSMPR CRYSTALLIZER

In this contribution, linearized dynamic model of Cumulative Mass Fraction (CMF) of Potassium Nitrate-Water Seeded Continues Mixed Suspension Mixed Product Removal (CMSMPR) crystallizer is approximated by a simplified model in frequency domain. Frequency domain model simplification is performed heuristically using the frequency response of the derived linearized models data. However, the CMF frequency response of the original model is obtained versus three input variables encompass seeding mass flow rate, inlet liquid volumetric flow rate and jacket temperature with emphasis on minimum model simplification assumptions. Results show that the simplified CMF frequency response predicts system dynamics and covers all system characteristics as well as the main complex model.

Melt suspension crystallization for purification of phosphoric acid

ABSTRACTA continuous melt suspension crystallization process has been presented for the purification of the phosphoric acid in this study, which is conducted in the cascade of a continuous mixed suspension and mixed product removal (MSMPR) crystallization and subsequent countercurrent solid–liquid contact in a gravity wash column. With magma withdrawn from the MSMPR crystallizer being fed into the top of the gravity wash column, crystals settle down toward the bottom of column and the reflux melt rises upward, whereas the sweating of crystals and counter‐current contact between crystal particles and the melt lead to high separation capability of impurities. The gravity wash column used in this study is a vertical agitated cylindrical column, whose configuration is different from the inclined column crystallizer. The feasibility of suspension crystallization equipment for purification of phosphoric acid was studied. Distribution of impurities in the wash column was also investigated as a function of the feed concentration, crystal bed height, reflux ratio and stirring speed. Reflux ratio has been found to play an important role in the process. Food grade phosphoric acid can be achieved when the process is operated with feed concentrations of 84 ~ 86 wt.%, reflux ratios of 3.4 ~ 6.2, stirring speed of 10 rpm and crystal bed height of 150 ~ 250 mm in a gravity wash column. © 2012 Curtin University of Technology and John Wiley &amp; Sons, Ltd.

Crystallization and Agglomeration Kinetics of Hydromagnesite in the Reactive System MgCl2–Na2CO3–NaOH–H2O

The reactive crystallization kinetics of hydromagnesite (4MgCO3·Mg(OH)2·4H2O) for the MgCl2–Na2CO3–NaOH–H2O system has been systematically investigated in a continuously operated mixed-suspension mixed-product removal (MSMPR) crystallizer for the first time. Determination of the effects of reactive temperature and OH– ion on magnesium carbonate hydrates in the above system was conducted through a batch crystallization experiment, and the crystallization temperature of 80 °C for the precipitation of regular spherical-like hydromagnesite was selected for the kinetics study. The relative supersaturation for hydromagnesite is obtained based on the activity coefficients calculated by the Pitzer model. The growth rate, nucleation rate, and agglomeration kernel are determined on the basis of the agglomeration population balance equation, and their kinetic equations are then correlated in terms of power law kinetic expressions. The orders of volume growth rate and linear growth rate with respect to the relative s...

Continuous Crystallization of Aliskiren Hemifumarate

Active ingredients in most pharmaceutical products are complex organic molecules that require crystallization as a purification and isolation step that results in a pure product at a high process yield. Knowledge of the operating conditions required to obtain crystals with the desired crystal shape, polymorph, and morphology is critical during process development. This paper describes a two-stage mixed suspension mixed product removal (MSMPR) continuous reactive crystallization procedure developed for Aliskiren hemifumarate. This process was able to crystallize Aliskiren hemifumarate at both high purity (>99%) and high yield (>92%). A model of the crystallization was developed through the simultaneous solution of a population balance equation, kinetic expression for crystal growth and nucleation, and a mass balance. Experimental data were fit to the model to obtain kinetic parameters for crystal growth and nucleation. After including equilibrium distribution coefficient data, the model was used to optimiz...

Development and Scale-Up of a Continuous, High-Pressure, Asymmetric Hydrogenation Reaction, Workup, and Isolation

A fully continuous process including an asymmetric hydrogenation reaction operating at 70 bar hydrogen, aqueous extraction, and crystallization was designed, developed, and demonstrated at pilot scale. This paper highlights safety, quality, and throughput advantages of the continuous reaction and separations unit operations. Production of 144 kg of product was accomplished in laboratory fume hoods and a laboratory hydrogenation bunker over two continuous campaigns. Maximum continuous flow vessel size in the lab hoods was 22 L glassware, and maximum plug flow tube reactor (PFR) size in the bunker was 73 L. The main safety advantages of running the hydrogenation reaction continuous rather than batch were that the flow reactor was smaller for the same throughput and, more importantly, the tubular hydrogenation reactor ran 95% liquid filled at steady state. Therefore, the amount of hydrogen in the reactor at any one time was less than that of batch. A two-stage mixed suspension–mixed product removal (MSMPR) cascade was used for continuous crystallization. Impurity rejection by continuous crystallization was superior to that by batch because scalable residence time and steady-state supersaturation enabled robust and repeatable control of enantiomer rejection in a kinetic regime, although this is a nonstandard approach, debatable as an impurity control strategy. The fully continuous wet-end process running in a laboratory infrastructure achieved the same weekly throughput that would be expected from traditional batch processing in a plant module with 400 L vessels.

Development of Continuous Anti-Solvent/Cooling Crystallization Process using Cascaded Mixed Suspension, Mixed Product Removal Crystallizers

This paper describes a two-stage mixed-suspension, mixed-product removal (MSMPR) continuous crystallization developed for a pharmaceutical intermediate which uses anti-solvent and cooling to generate supersaturation. The results indicate that the stage in which anti-solvent is added has a significant influence on the final crystal properties, while purity and yield were nearly identical. The population balance model was employed to determine growth and nucleation kinetics through parameter estimation. With the incorporation of measured equilibrium distribution coefficients, the model was used to optimize crystal purity and yield of the product with respect to operating temperature and residence time.

Melamine Crystallization: Physicochemical Properties, Interactions With Other Lithogenic Salts and Response to Therapeutic Agents

There were reports of children in the People's Republic of China being hospitalized with renal stones and/or failure by September 2008, which were caused by melamine and its co-contaminant cyanurate. We investigated the physicochemical behavior of melamine, its interaction with other endogenous urine factors and the response to therapeutic agents in the renal environment in vitro. A mixed suspension, mixed product removal system was set up for crystallization studies of melamine in urine. Crystallization kinetic parameters, including the nucleation and growth rates, and suspension density, were determined according to crystal number and size, as measured by a Coulter particle counter. Melamine crystallized out from urine under normal urinary conditions (pH 5.0 to 6.5) but crystallization was strongly inhibited at pH 4.5 or lower. Melamine significantly enhanced calcium oxalate precipitation while uric acid significantly decreased melamine crystallization. Bacteria mimicking urinary tract infection promoted melamine crystallization. Clinical relevant drugs, such as citrate and bicarbonate, significantly decreased melamine crystallization. This implies that melamine crystallizes under normal urinary conditions and can interact with other lithogenic salts and pose a significant risk for other stones. Urinary tract infection promotes melamine crystallization. Citrate and bicarbonate therapy are effective prophylactic agents against melamine induced crystallization.

A normal vector approach for integrated process and control design with uncertain model parameters and disturbances

In this work the normal vector method is extended to the simultaneous treatment of parametric uncertainty and disturbances. This method ensures that desired dynamic properties hold despite parametric uncertainty by maintaining a minimal distance between the operating point and so-called critical manifolds where the process behavior changes qualitatively. Here, unknown exogeneous disturbances and uncertain model and process parameters are considered simultaneously. To address this simultaneous problem formulation, the augmented systems developed for only parameterized disturbances in previous works have to be modified and extended. A generalized formulation of the robust optimization problem results, which includes normal vector constraints on critical manifolds of steady states and of bounds on the state transient. The numerical methods are further developed to prepare for the treatment of high-dimensional problems. Illustrative case studies considering the design of a continuous mixed-suspension mixed-product removal crystallization process and the Tennessee Eastman process are presented.

Scale-up Study of Agglomeration During Oxalic Precipitation in Nuclear Industry

The aim of this paper is to study the scale-up effects on agglomeration mechanisms during the precipitation of actinide and lanthanide oxalate in continuous MSMPR (Mixed Solution Mixed Product Removal) crystallizers in order to determine extrapolation rules from the laboratory scale to pilot and industrial scales. Precipitation experiments are performed in three identical steady-state continuous precipitators with a 20 scale-up factor. Under the same chemical and hydrodynamic conditions, the agglomeration kernel of neodymium oxalate obtained at small scale is valid on larger one. The results of this study allow to scale-up with success the data obtained at laboratory-scale to pilot even industrial scale.

Continuous Melt Suspension Crystallization of Phosphoric Acid

A continuous melt suspension crystallization process has been presented for the purification of the phosphoric acid in this study, which is performed in the cascade of a mixed suspension mixed product removal (MSMPR) crystallizer and a gravity wash column for the subsequent solid-liquid separation. Dynamic behavior in the crystallizer and role of reflux ration on the purification efficiency of column are studied in detail. A reasonable steady state with respect to the liquid phase is achieved after 2 to 3 hrs, which is followed by a solid-phase steady state in terms of the slurry density after 4 hrs. Reflux ratio is the effective parameter for separation and purification by the crystallization equipment from the influences of reflux ratio on the purity of product, the number of theoretical plates and the stability of the operations.

Seeding strategies and residence time characteristics of continuous preferential crystallization

This contribution investigates the effects of different seeding strategies and residence time characteristics on the dynamics of a Mixed Suspension Mixed Product Removal (MSMPR) crystallizer equipped with a fines dissolution unit. For the first time continuous preferential enantioselective crystallization is investigated. The fines dissolution is included as recycle streams around the MSMPR crystallizer. Moreover, primary heterogeneous and secondary nucleation mechanisms along with size-dependent growth rates are taken into account. A semi-discrete high resolution finite volume scheme (FVS) is employed for discretizing the derivatives with respect to the length coordinate. The resulting ordinary differential equations (ODEs) are solved by a Runge–Kutta method of order four. Several numerical case studies are carried out. The results support process design and optimization.

Urinary glycosaminoglycans and glycoproteins in a calcium oxalate crystallization system

This study measures the effects of total urinary glycosaminoglycans (GAGs), glycoproteins (GPs) and individual GAGs on the nucleation rates (Bo), growth rates (G) and suspension densities (Mт) of calcium oxalate (CaOx) crystallization by the mixed suspension mixed product removal (MSMPR) system. Total urinary GAGs, glycoproteins and individual GAGs including heparan sulfate (HS), chondroitin sulfate (CS) and Hyaluronic acid (HA) were added into the artificial urine (AU) and then introduced into the MSMPR test chamber and the crystal sizes and numbers were analyzed by a particle counter. The effects of added GAGs and GPs on CaOx crystallization were reflected by the changes on the crystallization indexes including the Bo, G and Mт of CaOx that were calculated based on the crystal size and numbers. Total urinary GAGs showed no statistical significance on CaOx crystallization. However, individual GAGs such as HA, CS and HS enhanced Bo and suppressed the G when measured individually. CS and HS enhanced the Mт while HA shown no significant change in the Mт of CaOx. Total urinary GPs showed an increase in the G and Mт of crystals. Although total urinary GAGs showed no statistically significant effect on CaOx crystallization, individual GAGs (CS, HS) promoted the CaOx crystallization by increasing the suspension density of smaller crystals, indicative of reduced risk of stones while HA showed no significance in the M T of CaOx formed. Urinary GPs indicated increased sizes and M T suggesting larger crystals and/or aggregates.