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 Process Model Approach to Predict Tablet Weight Variability for Direct Compression Formulations at Pilot and Production Scale

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1033
Author(s):  
Raghu V. G. Peddapatla ◽  
Gerard Sheridan ◽  
Conor Slevin ◽  
Shrikant Swaminathan ◽  
Ivan Browning ◽  
...  
Keyword(s):  
Process Model ◽  
Model Development ◽  
Processing Parameters ◽  
Pilot Scale ◽  
Direct Compression ◽  
Processing Conditions ◽  
Flow Properties ◽  
Production Scale ◽  
Optimum Processing ◽  
Relative Standard

Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). It identifies combinations of material and processing parameters ensuring that processing conditions achieve a targeted CQA. Optimum processing conditions are formulation and equipment-dependent. Therefore, it is challenging to translate a process design between formulations, pilot-scale and production-scale equipment. In this study, an empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. The CQA of interest was tablet weight variability, expressed as percentage relative standard deviation. An experimental design was executed for three model placebo blends with varying flow properties. These blends were compacted on one pilot-scale and two production-scale presses. The process model developed enabled the optimization of processing parameters for each formulation, on each press, with respect to a target tablet weight variability of <1%RSD. The model developed was successfully validated using data for additional placebo and active formulations. Validation formulations were benchmarked to formulations used for model development, employing permeability index values to indicate blend flow.

scholarly journals Scale-up of Aerated Industrial Multistage Rushton Impeller Bioreactors with Complex Rheology

2021 ◽  
Author(s):  
Sören Bernauer ◽  
Mathias Schöpf ◽  
Johannes Khinast ◽  
Timo Hardiman
Keyword(s):  
Scale Up ◽  
Power Input ◽  
Pilot Scale ◽  
Dimensionless Numbers ◽  
Industrial Fermentation ◽  
Liquid Mass Transfer ◽  
Pilot Scale Reactor ◽  
Fermentation Broths ◽  
Rushton Impeller ◽  
Scale Reactor

The power input and gas-liquid mass transfer rank among the most important industrial fermentation process parameters. The present study analyzes the power input and gas hold-up as a function of the flow regime, impeller diameter, and rheological properties in a pilot scale reactor (160 L) equipped with four Rushton impellers. This leads to four dimensionless numbers for predicting measurements in pilot and industrial bioreactors (110 and 170 m3) with a standard deviation of 7 % to 29 %. This is unparalleled for the underlying aerated and non-Newtonian fermentation broths. Several existing correlation equations are discussed to be dissatisfying (up to 130 % deviation), and might be sufficiently valid only within scale or for small scaling factors. The introduced approach predicts adequately accurate over three orders of magnitude. Based on these encouraging results, we identified the Galilei number and the power concept as the central elements in combination with the consequent dimensional analysis for an efficient scaling betweeen pilot and industrial scale.

scholarly journals Lean Six sigma Integration to Reduce Waste in Tablet coating Production with DMAIC and VSM Approach in Production Lines of Manufacturing Companies

2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Muhammad Kholil ◽  
Jakfat Haekal ◽  
Adizty Suparno ◽  
Dhita Savira Oktaandhini ◽  
Tri Widodo
Keyword(s):  
Six Sigma ◽  
Scale Up ◽  
Pilot Scale ◽  
Lean Six Sigma ◽  
Manufacturing Companies ◽  
Production Lines ◽  
Tablet Coating ◽  
Production Scale ◽  
Product Profile ◽  
Quality Target Product Profile

PT. Medica Indonesia was founded in 1969 and is one of the most significant ethical pharmaceutical companies in Indonesia. PT. Medica Indonesia, located in Cikarang, has a Pilot Plant Department that acts as a scale-up facility after lab scale to ensure that QTPP (Quality Target Product Profile) is consistently achieved on a pilot scale and a production scale. The high reject rate of 3.6% of the reject target of 0.5% for Tablet coating A products is a threat to the company because it can reduce productivity at PT. Medica Indonesia. Moreover, the Tablet coating A product is a mainstay product. In improving and improving the production line, it is necessary to identify the causes of waste. The integration of Lean Six Sigma using the DMAIC, VSM and VALSAT methods is an effective way to determine waste and the causes of waste. The analysis stage was carried out using the WRM and WAQ tools and determining recommendations for improvement using FMEA.

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.

Scale-Up of Wet Precipitation Calcium Phosphate Synthesis

2014 ◽  
Vol 604 ◽  
pp. 216-219 ◽  
Author(s):  
Marina Sokolova ◽  
Andris Putnins ◽  
Imants Kreicbergs ◽  
Janis Locs
Keyword(s):  
Calcium Phosphates ◽  
Scale Up ◽  
Chemical Precipitation ◽  
Pilot Scale ◽  
Precipitation Method ◽  
Technological Parameters ◽  
Wet Chemical ◽  
Pilot Scale Reactor ◽  
Scale Reactor ◽  
Wet Chemical Precipitation

Within current research calcium phosphates were synthesized by wet chemical precipitation method in laboratory and pilot scale reactor. The aim of this work was to study the influence of main technological parameters of wet chemical precipitation synthesis and scale-up of laboratory synthesis. The results showed that it is possible to obtain calcium phosphates with different and reproducible phase compositions such as hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP) and biphasic calcium phosphates (HAp/β-TCP) in pilot scale reactor. Using the method developed it was possible to increase the product yield more than 30 times compared to formerly used laboratory scale method.

scholarly journals Scale-Up of Decanter Centrifuges for the Particle Separation and Mechanical Dewatering in the Minerals Processing Industry by Means of a Numerical Process Model

Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 229
Author(s):  
Philipp Menesklou ◽  
Tabea Sinn ◽  
Hermann Nirschl ◽  
Marco Gleiss
Keyword(s):  
Process Model ◽  
Numerical Models ◽  
Scale Up ◽  
Mining Industry ◽  
Industrial Process ◽  
Numerical Approach ◽  
Pilot Scale ◽  
Numerical Process ◽  
Minerals Processing ◽  
Decanter Centrifuge

Decanter centrifuges are frequently used for thickening, dewatering, classification, or degritting in the mining industry and various other sectors. Their use in an industrial process chain requires a sufficiently accurate prediction of the product and the machine behaviour. For this purpose, experiments on a smaller pilot-scale are carried out for scale-up of a decanter centrifuge, which is usually a major challenge. Predicting the process behaviour of decanter centrifuges from laboratory tests is rather difficult. Basically, there are two common ways of scale-up: First, via analytical methods and the law of similarity, which often requires an enormous experimental effort. Second, using numerical models, which demands a mathematically and physically precise description of the multiple processes running simultaneously in such machines. This article provides an overview of both methods for scale-up of a decanter centrifuge. The concept of a previous developed numerical approach is introduced. Pros and cons of both scale-up methods are compared and further discussed. Experiments on lab-scale, pilot-scale, and industrial-scale decanter centrifuges with two different finely dispersed calcium carbonate water suspensions were carried out and simulations were done to investigate and prove the scale-up capability and transferability of the numerical approach.

Upscaling of foam forming technology for pilot scale

TAPPI Journal ◽  
2019 ◽  
Vol 18 (8) ◽  
Author(s):  
JANI LEHMONEN ◽  
TIMO RANTANEN ◽  
KARITA KINNUNEN-RAUDASKOSKI
Keyword(s):  
Production Efficiency ◽  
Strength Loss ◽  
Pilot Scale ◽  
Foam Density ◽  
Forming Process ◽  
Production Scale ◽  
Forming Technology ◽  
Wet Pressing ◽  
Foam Forming ◽  
Board Industry

The need for production cost savings and changes in the global paper and board industry during recent years have been constants. Changes in the global paper and board industry during past years have increased the need for more cost-efficient processes and production technologies. It is known that in paper and board production, foam typically leads to problems in the process rather than improvements in production efficiency. Foam forming technology, where foam is used as a carrier phase and a flowing medium, exploits the properties of dispersive foam. In this study, the possibility of applying foam forming technology to paper applications was investigated using a pilot scale paper forming environment modified for foam forming from conventional water forming. According to the results, the shape of jet-to-wire ratios was the same in both forming methods, but in the case of foam forming, the achieved scale of jet-to-wire ratio and MD/CD-ratio were wider and not behaving sensitively to shear changes in the forming section as a water forming process would. This kind of behavior would be beneficial when upscaling foam technology to the production scale. The dryness results after the forming section indicated the improvement in dewatering, especially when foam density was at the lowest level (i.e., air content was at the highest level). In addition, the dryness results after the pressing section indicated a faster increase in the dryness level as a function of foam density, with all density levels compared to the corresponding water formed sheets. According to the study, the bonding level of water- and foam-laid structures were at the same level when the highest wet pressing value was applied. The results of the study show that the strength loss often associated with foam forming can be compensated for successfully through wet pressing.

SAMPL6 Challenge Results from pKa Predictions Based on a General Gaussian Process Model

2018 ◽  
Author(s):  
Caitlin C. Bannan ◽  
David Mobley ◽  
A. Geoff Skillman
Keyword(s):  
Gaussian Process ◽  
Process Model ◽  
Molecular Graph ◽  
Gaussian Process Regression ◽  
Ionization State ◽  
Training Set ◽  
Physiochemical Properties ◽  
Quantile Plots ◽  
Physical And Chemical ◽  
Good Agreement

<div>A variety of fields would benefit from accurate pK<sub>a</sub> predictions, especially drug design due to the affect a change in ionization state can have on a molecules physiochemical properties.</div><div>Participants in the recent SAMPL6 blind challenge were asked to submit predictions for microscopic and macroscopic pK<sub>a</sub>s of 24 drug like small molecules.</div><div>We recently built a general model for predicting pK<sub>a</sub>s using a Gaussian process regression trained using physical and chemical features of each ionizable group.</div><div>Our pipeline takes a molecular graph and uses the OpenEye Toolkits to calculate features describing the removal of a proton.</div><div>These features are fed into a Scikit-learn Gaussian process to predict microscopic pK<sub>a</sub>s which are then used to analytically determine macroscopic pK<sub>a</sub>s.</div><div>Our Gaussian process is trained on a set of 2,700 macroscopic pK<sub>a</sub>s from monoprotic and select diprotic molecules.</div><div>Here, we share our results for microscopic and macroscopic predictions in the SAMPL6 challenge.</div><div>Overall, we ranked in the middle of the pack compared to other participants, but our fairly good agreement with experiment is still promising considering the challenge molecules are chemically diverse and often polyprotic while our training set is predominately monoprotic.</div><div>Of particular importance to us when building this model was to include an uncertainty estimate based on the chemistry of the molecule that would reflect the likely accuracy of our prediction. </div><div>Our model reports large uncertainties for the molecules that appear to have chemistry outside our domain of applicability, along with good agreement in quantile-quantile plots, indicating it can predict its own accuracy.</div><div>The challenge highlighted a variety of means to improve our model, including adding more polyprotic molecules to our training set and more carefully considering what functional groups we do or do not identify as ionizable. </div>

Catalytic asymmetric hydrogenation reaction by in situ formed ultra-fine metal nanoparticles in live thermophilic hydrogen-producing bacteria

Nanoscale ◽  
2021 ◽  
Author(s):  
Wei Bing ◽  
Faming Wang ◽  
Yuhuan Sun ◽  
Jinsong Ren ◽  
Xiaogang Qu
Keyword(s):  
Metal Nanoparticles ◽  
Catalytic Hydrogenation ◽  
Asymmetric Hydrogenation ◽  
Environmentally Friendly ◽  
Hydrogenation Reaction ◽  
Highly Efficient ◽  
Hydrogenation Reactions ◽  
Live Bacteria ◽  
Catalytic Asymmetric Hydrogenation

An environmentally friendly biomimetic strategy has been presented and validated for the catalytic hydrogenation reaction in live bacteria. In situ formed ultra-fine metal nanoparticles can realize highly efficient asymmetric hydrogenation reactions.

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