Scale-up Concerns

Reductions often pose scale-up concerns. The primary difficulty is that hydrogen is used or generated, which requires additional considerations and equipment for safe handling. At the end of a reaction, safely quenching any residual reducing capability is a concern on scale. Work-up can be tedious, especially if colloidal salts are formed. Disposing of metal salt by-products can be costly, and environmental concerns arise. Considerable attention to details is necessary to develop a reliable reduction for scale-up. In spite of these potential drawbacks, once the process has been developed and the appropriate equipment has been commissioned, reductions can be extremely reliable. 

Commercialization of new CFB processes for the production of chemicals— specialty or commodity—has been hindered due to scale-up concerns and operational complexity. In particular, the effect of diameter, high solids mass flux, and high pressure on gas hydrodynamics are undocumented in the open literature. Innovative research aimed at the design of new solids feeding devices and gas-solids separation techniques may reduce operational complexities. However, studies on small scale equipment must be performed prudently and documented concisely to be useful for scale-up. Scale effects at the entrance region are considerable, and sufficient attention has not been devoted to this region. 

There are scale-up concerns which are related to operations. In the laboratory, it is easy to observe what is happening. This makes extractions and phase separations a normal operation. We can charge materials and observe frothing or foaming. When die reaction is complete, it is very easy to evaporate solvents on a rotary evaporator. Those same operations are not as easy on large scale in closed vessels where the operator depends on charts, graphs, meters, and instruments. 

A client may choose to develop a toller who is qualified, but will need additional or improved equipment and technology to meet the eventual production levels required later in the life of the toll contract. The client may require the toller to make changes or modifications at their plant in order to effectively manufacture a particular product in increasing quantity. Some areas of concern applicable to scale up were listed in Various Points to Consider, Section 3.1. Additional considerations to address in the contract may include ... 

A toller may be operating the first scale-up of a process that has previously only been produced in pilot quantities. This pre-startup situation benefits when special concerns related to a scale-up are monitored. 

As far as industrial applications are concerned, the easy scale-up of two-phase catalysis can be illustrated by the first oxo aqeous biphasic commercial unit with an initial annual capacity of 100,000 tons extrapolated by a factor of 1 24,000 (batch-wise laboratory development production reactor) after a development period of 2 years [4]. 

The Br is a measure of the extent to which viscous heating is important relative to an impressed temperature difference. This can be of some concern in the scale-up design, v usually increasing, with other properties remaining constant. A comparison of the Br for a pilot scale (0.05-m screw) and an industrial (0.15-m screw) unit yields values of ca. 0.65, and 5.73, respectively, for the Br with A = 0.5 w/m K and rj = 500 Pa.s at 60 rpm. The numbers suggest that viscous dissipation will be important and will be much more pronounced in the case of an industrial unit. 

The scope to increase resource efficiency during scale up was shown to be large in the case studies assessed here. Therefore, efforts to implement methods such as mass balancing or LCA would pay off soon, since this would help to fully tap optimization potentials concerning ecology and economy. 

An important problem in emulsified organic-aqueous systems is that of scale-up, which is concerned with the realization of stable emulsions and the separation of phases after the reaction. The use of biphasic membrane systems that contain the enzyme and keep the two phases separated is likely to solve this problem. In the case of 5-naproxen an ee of 92% has been demonstrated without any decay in activity over a period of two weeks of continuous operation. A number of examples of biocatalytic membrane reactors have been provided by Giorno and Drioli (2000) and include the conversion of fumaric acid to L-aspartic acid, L-aspartic acid to L-alanine, and cortexolone to hydrocortisone and prednisolone. 

The consequence of all these (conscious and unconscious) simplifications and eliminations might be that some information not present in the process will be included in the model. Conversely, some phenomena occurring in reality are not accounted for in the model. The adjustable parameters in such simplified models will compensate for inadequacy of the model and will not be the true physical coefficients. Accordingly, the usefulness of the model will be limited and risk at scale-up will not be completely eliminated. In general, in mathematical modelling of chemical processes two principles should always be kept in mind. The first was formulated by G.E.P. Box of Wisconsin All models are wrong, some of them are useful . As far as the choice of the best of wrong models is concerned, words of S.M. Wheeler of New York are worthwhile to keep in mind The best model is the simplest one that works . This is usually the model that fits the experimental data well in the statistical sense and contains the smallest number of parameters. The problem at scale-up, however, is that we do not know which of the models works in a full-scale unit until a plant is on stream. 

Below, physical principles of basic separation and purification techniques are given and guidelines concerning collection of data that are needed or useful for scale-up of these unit operations. 

Distillation is a well-known process and scale-up methods have been well established. Many computer programs for the simulation of continuous distillation columns that are operated at steady state are available. In fine chemicals manufacture, this concerns separations of products in the production of bulk fine chemicals and for solvent recovery/purification. In the past decade, software for modelling of distillation columns operated at non-steady state, including batch distillation, has been developed. In the fine chemicals business, usually batch distillation is applied. 

Process Evaluation and Improvement. As homogeneous asymmetric hydrogenation processes are scaled up, one major concern is cost because the catalyst is usually expensive. Hence, several criteria for a commercially viable process (2), including selectively, conversion, catalyst loading (S/C, the molar ratio of substrate to catalyst), reaction time, and TOF (turnover frequency, the ratio of catalyst loading to reaction time), should be considered to evaluate the process and provide a guide for improvement. 

The facilities comprise a long list of equipment for lyophilization and vacuum-drying, formulation, filling, and packing. Projects may concern product or process development, scaling up or direct manufacturing (pilot or commercial scale). 

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