Scale-up methods

When choosing the scale-up method, changes in other flow/power parameters and their impact on the process result must be considered. Figure 11 shows changes in important parameters for different scale-up bases. For example, scale-up based on same tip speed maintains the T / Ubut decreases P/ Uby 80%. T / Uis almost always increased on scale-up. Scale-up based on the same P/ Umeans a reduction in mixer speed by 66%, which also... 

Tipnis, S. K., Penny, W. R., and Fasano, J. B., An experimental investigation to determine a scale-up method for fast competitive parallel reactions in agitated vessels, AIChE Annual Meeting, St. Louis, November 1993. 

Johnstone, R.E. and Thring, M.W., 1957. Pilot Plants, Models and Scale-up Methods in Chemical Engineering. New York McGraw Hill. 

These scale-up methods will necessarily at times include fundamental concepts, dimensional analysis, empirical correlations, test data, and experience [32]. 

Fauske and Associates, Inc., Flashing Viscous Flow of Polystyrene Mixtures Test Data and Scale-Up Methods, FAI/ 89-26, April 1989. 

Due to the complexity of the problem, it is generally accepted that we will not reach the optimal reactor design and ojjerating variables, but still we would like to design and operate the reactor safely and near the optimum. Further in this section, we will give a general discussion of. scale-up methods for chemical processes, in particular with respect to chemical reactors suitable for the manufacture of fine chemicals. Next, we will discuss how to obtain reasonable quantitative relationships necessary for optimal and safe scale-up according to the art. The reader can find an extensive treatment of scale-up problems in the book of Bisio and Kabel(1985). 

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. 

Lord, D.L. "Turbulent Flow of Stimulation Fluids An Evaluation of Friction Loss Scale Up Methods," SPE paper 16889, 1987 SPE Annual Technical Conference and Exhibition, Dallas, September 27 30. 

Choudhury, S., and L. Utiger, "Warmetransport in Ruhrkesseln Scale-up Methoden" ("Heat Transfer in Stirred Tanks Scale-up Methods"), Chem. Ing. Tech., 62,154-155 (1990). 

All of the principles and ideas covered in the previous section may be translated directly to the use of microorganisms as tools in the production of compounds of plant biosynthetic or biodegradative importance. Just as one finds microbial systems to be of value in preparing metabolites in mammalian systems, it may be possible to use microbial transformations to prepare derivatives of alkaloids that might be found rarely or only in very small quantities in plants. In this way, abundant prototype alkaloids may be used as microbial transformation substrates to provide a range of metabolites. As in the mammalian case, metabolism studies using plant tissues, tissue cultures, or cell-free extracts may be conducted in parallel with microbial metabolic systems. Metabolites common to both would be prepared in quantity by relatively simple fermentation scale-up methods. 

The first scale-up method was developed by Carley and McKelvey [1] in 1953. In this original work, the rate and power consumption at a fixed speed and for a geometrically similar extruder was simply a ratio of the extruder diameters as follows ... 

A new method for the preparation of soy sauce has been developed. The new scaled-up method divides the moromi process into two processes autolysis and fermentation. Because of the utilization of high temperatures, the new process permits the production of a NaCl free autolyzate from koji. Division of the fermentation process into two separated processes permit better control of lactic acid fermentation and alcohol fermentation processed which used to require great skill. The new scale-up procedure for soy sauce production yields a product in half the time required by the traditional (conventional) method and still produces a soy sauce with high levels of the desirable Bavor component, glutamic acid. Utilization of this protocol by the soy sauce producing industry should have significant economic impact to bo producers and consumers. 

Igor Gorsky, Richard K. Nielsen. Scale-up methods used in liquid pharmaceutical manufacturing. Pharm Technol 1992 16(9) 112-120. 

When planning an industrial-scale bioprocess, the main requirement is to scale up each of the process steps. As the principles of the unit operations used in these downstream processes have been outlined in previous chapters, at this point we discuss only examples of practical applications and scaling-up methods of two unit operations that are frequently used in downstream processes (i) cell separation by filtration and microfiltration and (ii) chromatography for fine purification of the target products. 

It was demonstrated that dimensional analysis of the tableting process can produce a scientifically reliable way of predicting tablet properties across the range of materials and with diverse compaction mechanisms. A theoretically sound scale-up method is thus readily available for tableting equipment of different capacity. The method can be readily expanded to include other materials and tablet presses and other target quantities, such as tablet stability (disintegration) and bioavailability (dissolution). 

The nonideal behavior also depends on reactor dimensions thus scale-up methods are sketched, in order to face the problems deriving from the industrial scale of those reactors. 

Rase [5] has presented several case studies of different scale-up methods involving industrially important reactions. Murthy [11] has provided a general guideline for the scale-up of slurry hydrogenation reactors, and other scale-up processes are illustrated elsewhere [12],... 

In general, the university graduate has not at all been adequately trained to deal with such problems. On the one hand, treatises on dimensional analysis, the theory of similarity and scale-up methods included in common, run of the mill textbooks on chemical engineering are out of date. In addition, they are only seldomly written in such a manner that would popularize these methods. On the other hand, there is no motivation for this type of research at universities since, as a rule, they are not confronted with scale-up tasks and are therefore not equipped with the necessary apparatus on the bench-scale. 

Such approaches underpin the current popularity of RP-HPLC procedures for the purification of synthetic or recombinant polypeptides at the production scale, or analogous approaches employed in the HP-IEX of commercially valuable proteins. However, in some cases when linear scale-up methods are applied to higher molecular weight polypeptides or proteins, their biological activity may be lost due to unfavorable column residency effects and sorbent surface area dependencies. It is thus mandatory that the design and selection of preparative separation system specifically address the issues of recovery of bioactivity. Often some key parameters can be easily controlled, i.e., by operating the preparative separation at lower temperatures such a 4°C, or by minimizing column residency times. 

When accurate data are not available in the literature or when past experience does not give an adequate design basis, pilot-plant tests may be necessary in order to design effective plant equipment. The results of these tests must be scaled up to the plant capacity. A chemical engineer, therefore, should be acquainted with the limitations of scale-up methods and should know how to select the essential design variables. 

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