scholarly journals Distinct and Quantitative Validation Method for Predictive Process Modeling with Examples of Liquid-Liquid Extraction Processes of Complex Feed Mixtures

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 298 ◽  
Author(s):  
Axel Schmidt ◽  
Jochen Strube
Keyword(s):  
Process Model ◽  
Process Development ◽  
Scale Up ◽  
Liquid Extraction ◽  
Process Models ◽  
Parameter Determination ◽  
Production Scale ◽  
Liquid Liquid Extraction ◽  
Safety Margins ◽  
Quantitative Validation

As of today, industrial process development for liquid-liquid extraction and scale-up of extraction columns is based on an experimental procedure that requires tests in pilot-scale. This methodology consumes large amounts of material and time and the utilized scale-up equations are crude estimates including considerable safety margins. This approach is practical for well-known systems or low-value products coupled with high production scale, where such a scale-up methodology has less impact on the overall profitability. However, for new high-value products in biologics manufacturing, a process development based on process understanding and the use of validated process models is imperative. Therefore, a distinct and quantitative validation workflow for liquid-liquid extraction modeling is presented on the example of two complex feed mixtures. Monte-Carlo simulations based on the presented model parameter determination concept result for both examples in prediction accuracy comparable to the experiments and prediction precision within the deviation of the respective experiments. Identification of statistically significant parameters is demonstrated. The presented methodology for model validation will support the implementation of liquid-liquid extraction in the manufacturing of new high value biological products in regulated industries by providing a workflow to derive a Quality-by-Design compatible process model.

scholarly journals Powerful Concentration of Rhodium in Plating Wastewater Using Homogeneous Liquid–Liquid Extraction (HoLLE) and Study for Scale-up

2017 ◽  
Vol 7 (4) ◽  
pp. 44 ◽  
Author(s):  
Takeshi Kato ◽  
Shotaro Saito ◽  
Shigekatsu Oshite ◽  
Shukuro Igarashi
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Aqueous Phase ◽  
Scale Up ◽  
Volume Ratio ◽  
Liquid Extraction ◽  
Optimum Conditions ◽  
Homogeneous Liquid ◽  
Liquid Liquid Extraction ◽  
Plating Wastewater

A powerful technique for the concentration of rhodium (Rh) in plating wastewater was developed. The technique entails complexing Rh with 1-(2-pyridylazo)-2-naphthol (PAN) followed by homogeneous liquid–liquid extraction (HoLLE) with Zonyl FSA. The optimum HoLLE conditions were determined as follows: [ethanol]T = 30.0 vol.%, pH = 4.00, and Rh:PAN = 1:5. Under these optimum conditions, 88.1% of Rh was extracted into the sedimented liquid phase. After phase separation, the volume ratio [aqueous phase (Va) /sedimented liquid phase (Vs)] of Va and Vs was 1000 (50 mL → 0.050 mL). We then applied the new method to wastewater generated by the plating industry. The phase separation was satisfactorily achieved when the volume was scaled up to 1000 mL of the actual wastewater; 84.7% of Rh was extracted into the sedimented liquid phase. After phase separation, Va/Vs was 588 (1000 mL - 1.70 mL).

scholarly journals Short Alternative Route for Nuclear Fuel Reprocessing Based on Organic Phase Self-Splitting

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6234
Author(s):  
Julie Durain ◽  
Damien Bourgeois ◽  
Murielle Bertrand ◽  
Daniel Meyer
Keyword(s):  
Organic Phase ◽  
Process Development ◽  
Temperature Drop ◽  
Extraction Process ◽  
Liquid Extraction ◽  
Nuclear Industry ◽  
Process Conditions ◽  
Joint Management ◽  
Liquid Liquid Extraction ◽  
Almost All

A more sustainable management of natural resources and the establishment of processes allowing a joint management of nuclear materials to avoid their diversion from their civilian use are two issues for the nuclear industry. Short alternatives to existing processes have therefore been proposed based on known systems available, tributylphosphate (TBP), for the separation of actinides by liquid/liquid extraction. Proof of concept of such alternative has been established on the uranium(VI)/thorium(IV) system. From an organic phase consisting of a mixture of TBP/n-dodecane loaded with uranium and thorium, two fluxes have been obtained: the first contains almost all of the thorium in the presence of uranium in a controlled ratio, the second contains surplus uranium. Two levers were selected to control the spontaneous separation of the organic phase: the addition of concentrated nitric acid, or the temperature variation. Best results have been obtained using a temperature drop in the liquid/liquid extraction process, and variations in process conditions have been studied. Final metal recovery and solvent recycling have also been demonstrated, opening the door for further process development.

Scale-Up of Protein Purification by Liquid-Liquid Extraction

1982 ◽  
pp. 69-74 ◽  
Author(s):  
M.-R. Kula ◽  
K. H. Kroner ◽  
H. Hustedt ◽  
H. Schutte
Keyword(s):  
Protein Purification ◽  
Scale Up ◽  
Liquid Extraction ◽  
Liquid Liquid Extraction

scholarly journals Systematic and Model-Assisted Process Design for the Extraction and Purification of Artemisinin from Artemisia annua L.—Part II: Model-Based Design of Agitated and Packed Columns for Multistage Extraction and Scrubbing

Processes ◽  
2018 ◽  
Vol 6 (10) ◽  
pp. 179 ◽  
Author(s):  
Axel Schmidt ◽  
Maximilian Sixt ◽  
Maximilian Huter ◽  
Fabian Mestmäcker ◽  
Jochen Strube
Keyword(s):  
Manufacturing Process ◽  
Process Model ◽  
Artemisia Annua ◽  
Scale Up ◽  
Plug Flow ◽  
Process Models ◽  
Extraction Column ◽  
Model Parameters ◽  
Multi Stage ◽  
Extraction And Purification

Liquid-liquid extraction (LLE) is an established unit operation in the manufacturing process of many products. However, development and integration of multistage LLE for new products and separation routes is often hindered and is probably more cost intensive due to a lack of robust development strategies and reliable process models. Even today, extraction columns are designed based on pilot plant experiments. For dimensioning, knowledge of phase equilibrium, hydrodynamics and mass transport kinetics are necessary. Usually, those must be determined experimentally for scale-up, at least in scales of DN50-150 (nominal diameter). This experiment-based methodology is time consuming and it requires large amounts of feedstock, especially in the early phase of the project. In this study the development for the integration of LLE in a new manufacturing process for artemisinin as an anti-malaria drug is presented. For this, a combination of miniaturized laboratory and mini-plant experiments supported by mathematical modelling is used. System data on extraction and washing distributions were determined by means of shaking tests and implemented as a multi-stage extraction in a process model. After the determination of model parameters for mass transfer and plant hydrodynamics in a droplet measurement apparatus, a distributed plug-flow model is used for scale-up studies. Operating points are validated in a mini-plant system. The mini-plant runs are executed in a Kühni-column (DN26) for extraction and a packed extraction column (DN26) for the separation of side components with a throughput of up to 3.6 L/h, yield of up to 100%, and purity of 41% in the feed mixture to 91% after washing.

scholarly journals LLECMOD: A Bivariate Population Balance Simulation Tool for Liquid- Liquid Extraction Columns

2008 ◽  
Vol 2 (1) ◽  
pp. 10-34 ◽  
Author(s):  
Menwer M. Attarakih ◽  
Hans-Jörg Bart ◽  
Tilmann Steinmetz ◽  
Markus Dietzen ◽  
Naim M. Faqir
Keyword(s):  
Energy Dissipation ◽  
Balance Equation ◽  
Scale Up ◽  
Population Balance ◽  
Liquid Extraction ◽  
Momentum Balance ◽  
Population Balance Equation ◽  
Simulation Tool ◽  
Modern Approach ◽  
Liquid Liquid Extraction

The population balance equation finds many applications in modelling poly-dispersed systems arising in many engineering applications such as aerosols dynamics, crystallization, precipitation, granulation, liquid-liquid, gas-liquid, combustion processes and microbial systems. The population balance lays down a modern approach for modelling the complex discrete behaviour of such systems. Due to the industrial importance of liquid-liquid extraction columns for the separation of many chemicals that are not amenable for separation by distillation, a Windows based program called LLECMOD is developed. Due to the multivariate nature of the population of droplets in liquid –liquid extraction columns (with respect to size and solute concentration), a spatially distributed population balance equation is developed. The basis of LLECMOD depends on modern numerical algorithms that couples the computational fluid dynamics and population balances. To avoid the solution of the momentum balance equations (for the continuous and discrete phases), experimental correlations are used for the estimation of the turbulent energy dissipation and the slip velocities of the moving droplets along with interaction frequencies of breakage and coalescence. The design of LLECMOD is flexible in such a way that allows the user to define droplet terminal velocity, energy dissipation, axial dispersion, breakage and coalescence frequencies and the other internal geometrical details of the column. The user input dialog makes the LLECMOD a user-friendly program that enables the user to select the simulation parameters and functions easily. The program is reinforced by a parameter estimation package for the droplet coalescence models. The scale-up and simulation of agitated extraction columns based on the populations balanced model leads to the main application of the simulation tool.

scholarly journals New Scale-up Technologies for Hydrogenation Reactions in Multipurpose Pharmaceutical Production Plants

2021 ◽  
Vol 75 (11) ◽  
pp. 948-956
Author(s):  
Thierry Furrer ◽  
Benedikt Müller ◽  
Christoph Hasler ◽  
Bernhard Berger ◽  
Michael K. Levis ◽  
...  
Keyword(s):  
Heat Transfer ◽  
Process Model ◽  
Scale Up ◽  
Pilot Scale ◽  
Hydrogenation Reaction ◽  
Production Scale ◽  
Hydrogenation Reactions ◽  
Scale Down ◽  
Physical And Chemical ◽  
Scale Reactor

The classical scale-up approach for hydrogenation reaction processes usually includes numerous laboratory- and pilot-scale experiments. With a novel scale-up strategy, a significant number of these experiments may be replaced by modern computational simulations in combination with scale-down experiments. With only a few laboratory-scale experiments and information about the production-scale reactor, a chemical process model is developed. This computational model can be used to simulate the production-scale process with a range of different process parameters. Those simulations are then validated by only a few experiments in an advanced scale-down reactor. The scale-down reactor has to be geometrically identical to the corresponding production-scale reactor and should show a similar mass transfer behaviour. Closest similarity in terms of heat transfer behaviour is ensured by a sophisticated 3D-printed heating/cooling finger, offering the same heat exchange area per volume and overall heat-transfer coefficient as in production-scale. The proposed scale-up strategy and the custom-designed scale-down reactor will be tested by proof of concept with model reactions. Those results will be described in a future publication. This project is an excellent example of a collaboration between academia and industry, which was funded by the Aargau Research Fund. The interest of academia is to study and understand all physical and chemical processes involved, whereas industry is interested in generating a robust and simple to use tool to improve scale-up and make reliable predictions.

scholarly journals Impact of Particle and Equipment Properties on Residence Time Distribution of Pharmaceutical Excipients in Rotary Tablet Presses

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 283
Author(s):  
Daniel Puckhaber ◽  
Sebastian Eichler ◽  
Arno Kwade ◽  
Jan Henrik Finke
Keyword(s):  
Residence Time ◽  
Time Distribution ◽  
Residence Time Distribution ◽  
Process Development ◽  
Continuous Production ◽  
Scale Up ◽  
Powder Flow ◽  
Production Scale ◽  
Influence Of Process Parameters ◽  
Custom Made

Paddle feeders are devices commonly used in rotary tablet presses to facilitate constant and efficient die filling. Adversely, the shear stress applied by the rotating paddles is known to affect the bulk properties of the processed powder dependent on the residence time. This study focuses on the residence time distribution (RTD) of two commonly applied excipients (microcrystalline cellulose, MCC; dicalcium phosphate, DCP), which exhibit different flow properties inside rotary tablet presses. To realistically depict the powder flow inside rotary tablet presses, custom-made tracer powder was developed. The applied method was proven to be appropriate as the tracer and bulk powder showed comparable properties. The RTDs of both materials were examined in two differently scaled rotary tablet presses and the influence of process parameters was determined. To analyze RTDs independent of the mass flow, the normalized variance was used to quantify intermixing. Substantial differences between both materials and tablet presses were found. Broader RTDs were measured for the poorer flowing MCC as well as for the production scale press. The obtained results can be used to improve the general understanding of powder flow inside rotary tablet presses and amplify scale-up and continuous production process development.

Miniature DIAMEX processes in a hollow fibre module micro-plant: process development and optimisation

2008 ◽  
Vol 96 (4-5) ◽  
Author(s):  
Andreas Geist ◽  
Klaus Gompper
Keyword(s):  
Process Development ◽  
Hollow Fibre ◽  
Liquid Extraction ◽  
Liquid Liquid Extraction ◽  
Plant Process

A hollow fibre module (HFM) micro-plant was built to perform continuous liquid-liquid extraction tests with very small feed volumes, using miniature HFM as phase contactors. Spiked DIAMEX tests (

scholarly journals Distinct and Quantitative Validation Method for Predictive Process Modelling in Preparative Chromatography of Synthetic and Bio-Based Feed Mixtures Following a Quality-by-Design (QbD) Approach

Processes ◽  
2019 ◽  
Vol 7 (9) ◽  
pp. 580 ◽  
Author(s):  
Steffen Zobel-Roos ◽  
Mourad Mouellef ◽  
Reinhard Ditz ◽  
Jochen Strube
Keyword(s):  
Quality By Design ◽  
Process Development ◽  
Model Development ◽  
Process Modelling ◽  
Feed Consumption ◽  
Parameter Determination ◽  
Preparative Chromatography ◽  
Maximum Information ◽  
Target Values ◽  
Quantitative Validation

Process development, especially in regulated industries, where quality-by-design approaches have become a prerequisite, is cost intensive and time consuming. A main factor is the large number of experiments needed. Process modelling can reduce this number significantly by replacing experiments with simulations. However, this requires a validated model. In this paper, a process and model development workflow is presented, which focuses on implementing, parameterizing, and validating the model in four steps. The presented methods are laid out to gain, create, or generate the maximum information and process knowledge needed for successful process development. This includes design of experiments and statistical evaluations showing process robustness, sensitivity of target values to process parameters, and correlations between process and target values. Two case studies are presented. An ion exchange capture step for monoclonal antibodies focusing on high accuracy and low feed consumption; and one case study for small molecules focusing on rapid process development, emphasizing speed of parameter determination.

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