Scale‐Up of Chemical Reactions

Stitt, E. Hugh; Simmons, Mark

doi:10.1002/9783527637140.ch6

Cited by 7 publications

(15 citation statements)

References 33 publications

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“…For example, reactions such as lithiations are typically carried out at −78 °C (the sublimation point of dry ice), but on industrial scale, the increased viscosity and low solubility of such a solution can lead to inhomogeneity and possibly impurity formation. In the downstream process, problems include large-scale liquid–liquid extraction (formation of emulsions) and the need to tightly control the crystallization process (polymorphism and solvate formation) of every batch (Laird, 2010; Stitt and Simmons, 2011). Moreover, the very nature of the step-by-step process requires many manual operations.…”

Section: Approaches For Resupply Of Pharmacologically Active Plantmentioning

confidence: 99%

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Atanasov

Waltenberger

Pferschy‐Wenzig

et al. 2015

Biotechnology Advances

2,217

1,385

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Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis.While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

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Section: Approaches For Resupply Of Pharmacologically Active Plantmentioning

confidence: 99%

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Atanasov

Waltenberger

Pferschy‐Wenzig

et al. 2015

Biotechnology Advances

2,217

1,385

View full text Add to dashboard Cite

show abstract

“…The Kolmogoroff microscale of turbulence ( λ k ) is dependent on energy dissipated in the fermenter and liquid kinematic viscosity ( µ k ), which can be indicative of mechanical damage to microbial cells (Stitt and Simmons 2011 ) and was calculated using (Eq. 7 ): …”

Section: Methodsmentioning

confidence: 99%

“…10 . The P o value (5) for turbulent flow was determined from R e vs P o power correlation graph (Stitt and Simmons 2011 ). Consequently, the mixing power consumption (P) for 300 m 3 fermentation was calculated using Eq.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, six different impeller types were selected combining five different agitation speed to design a suitable impeller type and speed for an industrial scale fermenter. The selected impeller types (Rushton turbine blade (RTB), Lightnin A310 three blade hydrofoil (LA310), Lightnin A315 four-blade hydrofoil (LA315), concave blade turbine (CBT), pitched blade turbine (PBT) and Marine propeller (MP)) are widely employed for mixing the fermentation liquids (Markopoulos and Pantuflas 2001 ; Stitt and Simmons 2011 ; Petříček et al 2018 ). The selected agitation speeds (0.83, 1.33.…”

Section: Methodsmentioning

confidence: 99%

“…The background data for electricity production were obtained from the Sustainable Energy Authority of Ireland (SEAI 2020 ) and Ecoinvent database (v3.1) considering geographic location as Ireland. In standard large scale fermenter operations, the working volume remains around 70–80% of the total fermenter volume (Stitt and Simmons 2011 ), which dictates the number of impellers to be used and subsequently the energy consumed. In other words, the reduction in Z values could reduce the number of impellers employed (Eq.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Upscale fermenter design for lactic acid production from cheese whey permeate focusing on impeller selection and energy optimization

et al. 2021

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This study focusses on the design and scale-up of industrial lactic acid production by fermentation of dairy cheese whey permeate based on standard methodological parameters. The aim was to address the shortcomings of standard scale-up methodologies and provide a framework for fermenter scale-up that enables the accurate estimation of energy consumption by suitable selection of turbine and speed for industrial deployment. Moreover, life cycle assessment (LCA) was carried out to identify the potential impacts and possibilities to reduce the operation associated emissions at an early stage. The findings showed that a 3000 times scale-up strategy assuming constant geometric dimensions and specific energy consumption (P/Vw) resulted in lower impeller speed and energy demand. The Rushton turbine blade (RTB) and LightninA315 four-blade hydrofoil (LA315) were found to have the highest and lowest torque output, respectively, at a similar P/Vw of 2.8 kWm−3, with agitation speeds of 1.33 and 2.5 s−1, respectively. RTB demonstrating lower shear damage towards cells (up to 1.33 s−1) was selected because it permits high torque, low-power and acceptable turbulence. The LCA results showed a strong relation between the number of impellers installed and associated emissions suggesting a trade-off between mixing performance and environmental impacts.

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Statistical optimization, kinetic modeling, and techno-economic analysis for the production of high molecular mass dextran using sugarcane industrial waste-molasses

Rahman,

Pasupathi,

Karuppiah

2024

Bioresource Technology Reports

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Scale‐Up of Chemical Reactions

Cited by 7 publications

References 33 publications

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Discovery and resupply of pharmacologically active plant-derived natural products: A review

Upscale fermenter design for lactic acid production from cheese whey permeate focusing on impeller selection and energy optimization

Statistical optimization, kinetic modeling, and techno-economic analysis for the production of high molecular mass dextran using sugarcane industrial waste-molasses

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