Scale Up

The supply of oxygen by aeration-agitation conditions are closely related to the following parameters  

Based on these three parameters, the four scale-up methods have been investigated keeping each parameter constant from laboratory to industrial scale. The parameters for scale-up are the following  

Even for the simple stirred, aerated fermenter, there is no one single solution for the scale-up of aeration-agitation which can be applied with high probability of success for all fermentation processes. Scale-up methods based on aeration efficiency (kio) or power consumption/unit volume have become the standard practice in the fermentation field. 

The ORP value Ef, in a non-biological system at a constant temperature is given in the following equation  

= the potential vs hydrogen electrode In microbial culture systems, the ORP value E can be expressed as follows  

Sizing of full scale equipment on the basis of small scale tests requires a consideration of possible ranges of at least the following variables  

operating conditions, particularly pressure and high initial ratcs  

Safety factors for scale up from laboratory leaf tests are difficult to generalize. On the basis of pilot plant work, adjustments of 11-21% are made to plate-and-frame filter areas or rates, and 14-20% to continuous rotary filters, according to Table 1.4. 

The performance of solid-liquid separation equipment is difficult to predict by the engineer without some specific experience in this area. Unfortunately, it must be again recommended that the 

Equipment for solid-liquid separation is available commercially from many sources. About 150 names and addresses of suppliers in the United States and abroad are listed by Purchas (1981). Classifications of vendors with respect to the kind of equipment are given, for instance, in Chemical Engineering Catalog (Reinhold, New York, annual) and in Chemical Engineering Equipment Buyers Guide (McGraw-Hill, New York, annual). 

We have stated that dimensional analysis results in an appropriate set of groups that can be used to describe the behavior of a system, but it does not tell how these groups are related. In fact, dimensional analysis does not result in any numbers related to the groups (except for exponents on the variables). The relationship between the groups that represents the system behavior must be determined by either theoretical analysis or experimentation. Even when theoretical results are possible, however, it is often necessary to obtain data to evaluate or confirm the adequacy of the theory. Because relationships between dimensionless variables are independent of 

This is valid for any Newtonian fluid in any (circular) pipe of any size (scale) under given dynamic conditions (e.g., laminar or turbulent). Thus, if the values of jV3 (i.e., the Reynolds number 7VRe) and /V, (e/D) for an experimental model are identical to the values for a full-scale system, it follows that the value of N6 (the friction factor) must also be the same in the two systems. In such a case the model is said to be dynamically similar to the full-scale (field) system, and measurements of the variables in N6 can be translated (scaled) directly from the model to the field system. In other words, the equality between the groups /V3 (7VRc) and N (e/D) in the model and in the field is a necessary condition for the dynamic similarity of the two systems. 

Because this is the only variable that is needed to describe this system, it follows that the value of this group must be the same, i.e., a constant, for the 

As an example of the application of dimensional analysis to experimental design and scale-up, consider the following example. 

Example 2-3 Scale-Up of Pipe Flow. We would like to know the total pressure driving force (AP) required to pump oil (/z = 30 cP, p = 0.85 g/cm3) through a horizontal pipeline with a diameter (D) of 48 in. and a length (L) of 700 mi, at a flow rate (Q) of 1 million barrels per day. The pipe is to be of commercial steel, which has an equivalent roughness (e) of 0.0018 in. To get this information, we want to design a laboratory experiment in which the laboratory model (m) and the full-scale field pipeline (f) are operating under dynamically similar conditions so that measurements of AP in the model can be scaled up directly to find AP in the field. The necessary conditions for dynamic similarity for this system are 

The chiral screen uses columns of 10 cm length, high flow rates, and fast gradients [3, 4, 13], An initial assessment with methanol as the modifier and the four columns is run serially, followed by screens using ethanol and isopropanol. One racemate can be analyzed in 80 min, making it possible to screen several samples overnight, to isolate rapidly small amounts on the analytical system and to scale up to the preprative system on the next day. The authors report a success rate of 90%. 

In situations where larger amounts, low concentration impurities or dilute feed need to be processed, a more detailed assessment and chromatography process development is advisable. Time frequently is the most stringent driver in addition to the constraints mentioned above. The purpose of the process development is to maximize throughput while maintaining acceptable robustness. Two limiting 

A simple spreadsheet tool can be used to capture the results of the fraction analyses, provide data visualization, integrate the responses, and thereby establish starting points for the fraction collection window(s), estimation of target purity and amount recovered. This data is useful for extrapolating the number of 

Developing an isolation approach is an activity that is frequently overlooked or addressed as an afterthought. However, solubility and stability data may dictate the development of a chromatographic method that requires the elaboration of the isolation, that is, it is more complicated than a simple evaporation of the mobile phase. The development of the chromatographic process should be linked to and interactively codeveloped with the isolation. Ideally, the isolated impurity sample should not contain other compounds or artifacts, such as solvents, mobile-phase additives or particulate matter from the preparative chromatography, as they may interfere with the structure elucidation effort or adversely affect the stability of the impurity during the isolation process. Therefore, it is preferable to avoid or minimize the use of mobile-phase additives. However, should this prove to be impossible, the additive used should be easy to remove. The judicious choice of mobile phase in the HPLC process increases the ability to recover the compound of interest without or with minimum degradation. The most common 

Polyethylene The first commercial fluidized-bed polyethylene plant was constructed by Union Carbide in 1968. Modern units operate at a temperature of approximately 100°C and a pressure of 

The ESD data in a stirred vessel has hardly been reported, and therefore, it must be clarified. Further, whether the new ESD defined by Eq. (4.7) can apply to the measured results must also be clarified. 

Fluid ion exchange water and 10wt% aqueous glycerin solution (involves 0.5 mole/1 KC1, 3 x 10-3 mole/1 K4Fe(CN)6 and K3Fe(CN)6). 

After it is confirmed that the flow in the vessel has attained a steady state under a fixed Re, the velocity fluctuations are measured at the fixed impeller discharge flow region by using an electrode reaction velocity meter. The measured ESD is fitted by the new ESD defined by Eq. (4.7). 

Challenge 4.3. Reliability of traditional scale-up rule of a stirred vessel n 13-18 19 

If the calculated degassing performance on the laboratory machine differs from the 

The applied vacuum levels and temperatures along the process section in the laboratory machine and the production machine should be identical. This can be scaled up with a sufficient degree of precision using computation programs or empirical values. 

Now conies a critical stage learning to make large amounts of product. You need these for testing, both by yourself and by customers or potential customers. 

Design and Development of Biological, Chemieal, Food and Pharmaceutieal Products S. Kiil and M.E. Vigild 2007 John Wiley Sons, Ltd 

A tabletting machine makes hundreds of thousands of tablets per hour. The time available for filling the tablet cylinder is only a few microseconds, so the flow properties of the binder powder are important. In addition the tablet piston has to be lubricated, and the lubricant can 

We can avoid sticking problems by keeping the particles cool and dry. However, the particles must be large enough, both in the small and the large experiments. 

You want to use a small machine for development, and a large machine for production. The small machine should be as small as practical to allow quick and flexible experimentation. The size of the large machine is dictated by the required throughput unless (as here) it already exists. We shall see that this requires a different approach to the design of the atomizers. As 

Moving from batch experiments to continuous reactors, one major problem is to ensure a good flow of the material inside the reactor (mechanical aspect). The efficiency of the global process depends not only on the material transport in the reactor, but also on the heat transfer to and inside the material. The feed preparation is then essential as well as the characterization of the eventual side material (water, metals, minerals, pollutants, etc.). 

The different pyrolysis and gasification technologies, selected in relation to the waste input, generate different kinds of products that will have to be upgraded into substitution fuels. The solid fuel could be upgraded by mechanical separation of metals and minerals in order to produce a cheap feedstock to a classical gasifier. Moreover, selected additions during pyrolysis could entrap pollutants such as chlorine and heavy metals [2,3,63,64]. 

Interactions during pyrolysis of waste containing plastics in the presence of wood contaminated by chlorine and heavy metals have been studied at laboratory scale. The chlorine capture and the inhibition the chlorination of heavy metals has been validated at pilot scale [1]. 

The quality of the gases and oils has to be certified by analytical tests in order to be accepted for valorization as substitutions fuels [5]. 

one must decide whether a radial or axial flow impeller, or some combination, is needed. 

Axial flow impellers produce less radial flow, and much more axial flow for similar power input (as the name suggests). They therefore produce much more vertical mixing when so oriented. They also do a much better job mixing between the region above and below the impeller. 

Since radial flow impellers generally produce a higher turbulence zone and axial flow impellers produce more vertical vessel flow, a good combination in applications where two or more impellers are used is to use a radial flow impeller near the bottom where the feed is introduced, and one or more axial flow impellers on the same shaft above it to provide vertical mixing and induce flow through the otherwise partially segregated region under the radial flow impeller. 

It should be noted, however, all the energy input to an impeller or system of impellers is dissipated by the flow in the vessel, regardless of the type of impeller(s). What does change with the type impeller(s), of course, is the overall flow field in the vessel and the spatial dissipation of the energy dissipation. Turbulent energy is dissipated, as noted above, by the smallest scales of turbulence, so of course the spatial distribution of dissipation and turbulence intensity are closely related. 

Industrial crystallization has the (at least partially deserved) reputation of being difficult to scale-up. If one considers that, as stated at the outset of this chapter, individual crystals respond only to their micro-environment and that mixing determines how the micro- and macroenvironments in the crystallizer interact as well as their spatial and temporal homogeneity, it is clearly mixing that determines the ease or difficulty of scaling this process. 

In the end as co-crystalline materials move further into development and become viable options as marketed products, scalable co-crystal processes must be evaluated and optimized. 

Furthermore, as for single-component systems, determining the thermodynamic relationship between polymorphs of co-crystals is very important, because, as it has been stated previously, changes in crystal form can lead to dilferences in physical and chemical properties. So conducting a thorough polymorph screen of a particular co-crystal of interest is highly valuable, just as it is for a single-component crystalline material. 

No doubt, polymorph screening of co-crystals will continue to attract more attention as these materials continue to gain momentum as another solid form choice in the development of new pharmaceuticals. As with salts, co-crystal polymorphs offer additional options to alter properties, increase patent protection, and improve marketed formulations. 

This chapter has outlined the role of co-crystals within the pharmaceutical development continuum. It can clearly be seen that co-crystals have their rightful place as useful solid forms within the industry. Major solid-state 

---

Remer, D. S., and Chai, L. H., Design Cost Factors for Scaling-up Engineering Equipment, Chem. Engg. Progr., 86 Aug. 77, 1990. 

TATTERSON Fluid Mixing and Gas Dispersion in Agitated Tanks TATTERSON Scale-up of Industrial Mixing Processes VVILLIG Environmental TQM... 

First she lists the equipment, next the reagents.. Also, noted are the book s quantity and her dream of a 5x scale up ... 

The above dream was scaled up in exact portions, as it was her first Her next dream had some variations to weights and measures, plus a longer reaction time... 

The above synthesis, although performed on a small scale, is easily scaled up to industrial size (French Pat. 2,669,922, CA 118 P6734U). It is a general procedure for substituting aryl-Br with -OMe or -OEt, giving us the possibility to produce other compounds from already known substances, e.g bromination of MDA yields 6-Br-MDA. This is converted by the above procedure to MMDA-2, 133, active at 25-50mg, 8-12 hrs. 

All of this careful addition is to keep the reaction from starting before the bomb is sealed. It is also important to note that the chemist must scale up or scale down the amount of reactants so that the total amount of all the ingredients consumes no less than 90 of the volume space of her particular pipe bomb. Too much head space with its atmospheric air will lower the yield. The bomb is heated in an oil bath or oven at 105-115°C for 18-24 hours and the contents are then distilled with the 1,3 benzodioxole coming over at about 170-175°C with no vacuum, Alternatively, the chemist can only distill off the methanol, wash with dilute NaOH solution and extract with ether, etc. 

As a result of a variable liquid-junction potential, the measured pH may be expected to differ seriously from the determined from cells without a liquid junction in solutions of high acidity or high alkalinity. Merely to affirm the proper functioning of the glass electrode at the extreme ends of the pH scale, two secondary standards are included in Table 8.14. In addition, values for a 0.1 m solution of HCl are given to extend the pH scale up to 275°C [see R. S. Greeley, Anal. Chem. 32 1717 (I960)] ... 

The change in interaction energy per 1,2 pair is thus h. Aw. Next we must consider how this scales up for a large array of molecules, and particularly how to describe the concentration dependence of the result. 

S. M. Wheelwright, Protein Purification Design and Scale-up of Downstream Processing, Hanser PubHshers, Munich, Germany, 1991, pp. 1—9, 61, 213—217. 

Little is known of the market for acetyl chloride. The production and sales are beUeved to be small, but may have potential for very large scale-up. The total U.S. market may amount to only 500 t annually. Acetyl chloride must be shipped in polyethylene-lined dmms having capacities of only 220 L it must be labeled as a corrosive substance. Acetyl chloride generated captively from purchased raw materials probably has a unit value of no more than 0.92—0.95/kg. Shipping costs and other factors set the price at about 3/kg for the commercial trade. 

After development of a new process scheme at laboratory scale, constmction and operation of pilot-plant faciUties to confirm scale-up information often require two or three years. An additional two to three years is commonly required for final design, fabrication of special equipment, and constmction of the plant. Thus, projections of raw material costs and availabiUty five to ten years into the future become important in adopting any new process significantly different from the current technology. 

Eor design of a large-scale commercial extractor, the pilot-scale extractor should be of the same type as that to be used on the large scale. Reflable scale-up for industrial-scale extractors still depends on correlations based on extensive performance data collected from both pilot-scale and large-scale extractors covering a wide range of Hquid systems. Only limited data for a few types of large commercial extractors are available in the Hterature. 

Scale-up and performance of a 1.47-m Scheibel column have been reported (98,154,155), as have detailed description and design criteria for the Scheibel column (156) and scale-up procedures (157). The same stage efficiency can be maintained on scale-up, and total throughput can be increased by three and one-half times at the expense of higher HETS. As of this writing, Scheibel columns up to 2.75 m in diameter are in service. 

The rotating-disk contactor (RDC), developed in the Netherlands (158) in 1951, uses the shearing action of a rapidly rotating disk to interdisperse the phases (Eig. 15b). These contactors have been used widely throughout the world, particularly in the petrochemical industry for furfural [98-01-1] and SO2 extraction, propane deasphalting, sulfolane [126-33-0] extraction for separation of aromatics, and caprolactam (qv) [105-60-2] purification. Columns up to 4.27 m in diameter are in service. An extensive study (159) has provided an excellent theoretical framework for scale-up. A design manual has also been compiled (160). Detailed descriptions and design criteria for the RDC may also be found (161). 

The Oldshue-Rushton column (Eig. 15d) was developed (162) in the early 1950s and has been widely used in the chemical industry. It consists essentially of a number of compartments separated by horizontal stator-ring baffles, each fitted with vertical baffles and a turbine-type impeller mounted on a central shaft. Columns up to 2.74 m in diameter have been reported in service (162—167). Scale-up is reported to be reliably predictable (168) although only limited performance data are available (169). A detailed description and review of design criteria are available (170). 

B. F. Warner, joint symposium. The Scaling-Up of Chemical Plant and Processes, London, 1957, p. 44. 

Scale-Up Proceduresfor a Scheibel Extraction Column, NTIS Report No. DE3-013576, National Technical Information Service, U.S. Department of Commerce, Washington, D.C., 1983. 

One of the areas critical to the MCVD process was understanding the chemistry of the oxidation reactions. It was necessary to control the incorporation of Ge02 while minimizing OH formation. Additionally, understanding the mechanism of particle formation and deposition was critical to further scale-up of the process. 

Although this first route was simple in concept, it proved slow in operation, difficult to scale up safely, and relatively uneconomical compared with the other routes. Denitration of the fibers, necessary to allow safe use wherever the fabrics may risk ignition, spoiled their strength and appearance. Nevertheless, Chardoimet earned and truly deserved his reputation as the Eather of Rayon. His process was operated commercially until 1949 when the last factory, bought from the Tubize Co. in the United States in 1934 by a Bra2iUan company, burned down. 

The scale-up of conventional cake filtration uses the basic filtration equation (eq. 4). Solutions of this equation exist for any kind of operation, eg, constant pressure, constant rate, variable pressure—variable rate operations (2). The problems encountered with scale-up in cake filtration are in estabHshing the effective values of the medium resistance and the specific cake resistance. 

The axial filter (Oak Ridge National Laboratory) (30) is remarkably similar to the dynamic filter in that both the rotating filter element and the outer shell are also cylindrical. An ultrafiltration module based on the same principle has also been described (31). Unlike the disk-type European dynamic filters described above, the cylindrical element models are not so suitable for scale-up because they utilize the space inside the pressure vessel poorly. 

---