Scale-up of procedure

A scale-up " of procedure II for plant prepn, according to Ref 8, is as follows ... 

The scale-up of filtration centrifuges is usually done on an area basis, based on small-scale tests. Buchner funnel-type tests are not of much value here because the driving force for filtration is not only due to the static head but also due to the centrifugal forces on the Hquid in the cake. A test procedure has been described with a specially designed filter beaker to measure the intrinsic permeabiHty of the cake (7). The best test is, of course, with a small-scale model, using the actual suspension. Many manufacturers offer small laboratory models for such tests. The scale-up is most reHable if the basket diameter does not increase by a factor of more than 2.5 from the small scale. 

A few excellent books are also available on reaction engineering in the widest sense and from a fundamental point of view. These books treat the subject with mathematical rigor, yet are too inclusive to have any space left for details on experimental procedures. Here, the reader can find more insight and practical examples on the development and scale-up of... 

The usual procedure for scale-up of a fermenter based on concepts is well known. The following criteria are translated between two scales of operation. They are selected as a procedure for scale-up. 

The main role of pilot plant is in the scale-up of polymer formulations from laboratory to full scale production and the development of new processes and techniques, including trials of new equipment. The laboratory is normally where the chemistry of new products and processes is investigated and established. When scale-up is contemplated, the use of commercial quality materials will normally be investigated, test procedures established and certain processing tolerances examined. An experienced chemist can frequently learn much on the laboratory scale that will indicate likely scale-up behaviour, but it is always prudent to then go through the pilot stage before embarking on full scale production. 

Ultrasound can thus be used to enhance kinetics, flow, and mass and heat transfer. The overall results are that organic synthetic reactions show increased rate (sometimes even from hours to minutes, up to 25 times faster), and/or increased yield (tens of percentages, sometimes even starting from 0% yield in nonsonicated conditions). In multiphase systems, gas-liquid and solid-liquid mass transfer has been observed to increase by 5- and 20-fold, respectively [35]. Membrane fluxes have been enhanced by up to a factor of 8 [56]. Despite these results, use of acoustics, and ultrasound in particular, in chemical industry is mainly limited to the fields of cleaning and decontamination [55]. One of the main barriers to industrial application of sonochemical processes is control and scale-up of ultrasound concepts into operable processes. Therefore, a better understanding is required of the relation between a cavitation coUapse and chemical reactivity, as weU as a better understanding and reproducibility of the influence of various design and operational parameters on the cavitation process. Also, rehable mathematical models and scale-up procedures need to be developed [35, 54, 55]. 

The solution of these problems is based on a simple idea the developed laboratory-scale process is used for manufacturing of a chemical product by parallelization of many small units. Although promising great advantages over scale-up, this procedure, denoted numbering-up , is not trivial by far. It cannot be carried out in a simple way due to the tremendous technological effort necessary a chemical plant with hundreds or even thousands of small-scaled vessels, stirrers, heaters, pumps. 

Process development with particular attention to process profitability and safety and minimization of the environmental impact is presented in Chapter 5. A brief description of the present practice in scale-up, development, and production planning is given and the most promising trends and achievements are presented. Recommendations are given how to achieve success in the scale-up of a process a successful scale-up can be defined as the procedure that allows the same yields and product distribution in a full-scale plant as on a small scale. 

Until about the second World War chemical processes were developed in an evolutionary way by building plants of increasing size and capacity. The capacity of the next plant in the series was determined by a scale-up factor that depended mainly upon experience gained from scale-ups of similar plants. Due to a lack of predictive models for chemical processes and operations, processes had to be scaled up in many small steps. This procedure was very expensive and the results unreliable. Therefore, large safety margins were incorporated in scale-up procedures, which often resulted in a significant unintended overcapacity of the designed plant. 

In preparation for scale-up of the strigol synthesis described by Sih (8), efforts were made to improve the yield of some of the seven steps involved in the scheme. Of these steps, nine are satisfactory from the standpoint of yield and experimental conditions. For three of the steps, we have improved the yield and/or experimental conditions such that the yield of (+ )-strigol would be raised to 2.85% overall from citral rather than 1.53% based on Sih s procedure and reported yields. Improvements were developed preparation of a-cyclocitral (III), the oxidation of the hydroxyaldehyde (V) to the ketoacid (VII), and for the preparation of the hydroxybutenolide (XVII). For the remaining five steps, our attempts to change experimental conditions have failed to improve, and in most cases to even obtain, the yields reported in the literature (8). We have considered the preparation of strigol analogs and determined the conditions and limitations for the preparation of a series of alkoxybutenolides (XVI) and a butenolide dimer (XVIII). Modification of the literature procedure (11) to eliminate the use of the mesylate (XX) and the use of polar aprotic solvents gave better yields of the 2-RAS (XXI). 

A mixture of sodamide, bromoanisole, and l-methoxy-2-methyl-l-(trimethylsilyl-oxy)-l-butene were reacted at room temperature at a 50 millimolar scale. After some two horns, with slight emission of ammonia, the reaction suddenly became exothermic, with violent gas emission and on one occasion a fire. This was a modest scale-up of a literature procedure for synthesis of 2-alky lbenzoic acids, via a benzyne intermediate. It is advised that this reaction be employed only on smaller scale, with safety precautions. The reaction must pass through a benzocyclobutane intermediate, this, or another, high energy species might accumulate and then decompose. 

The initial synthesis and resolution of 88 was performed as a one-step procedure with the resolving agent added to the reaction mixture after addition of PCI5 <1997AGE608>. An improved two-step procedure enabled the scale-up of the reaction from a 100mg scale to a 40g scale <1998TL4825, 2004JOC8521>. 

In scaling up this procedure, the biggest improvement in the overall yield was achieved by omitting the crystallization of the intermediate diol. The trans-2-phenylcyclohexanol, which forms relatively large crystals, is easier to handle lhan the diol, which is a very fluffy powder. Analysis of the final product was carried out by both CSP-HPLC and CSP-SFC methods. 

Scale-up of spin-filters has been often studied in the recent years, and simple scale-up procedures have been proposed by Yabannavar et al. [81] and Deo et al. [13]. Yabannavar et al. [81] suggested a procedure based on keeping the ratio of permeation drag to lift force constant for the different production scales, in... 

Rapid production scale-up procedures. If these procedures are established before they are needed, they can be implemented immediately in an attack. Although investigation into scale-up of all stages of production should occur, the scale-up of separation and purification is a specific challenge. 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen (55), referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and... 

When a process is dominated by a mixing operation, another gambit for the effective scale-up of geometrically similar systems involves the interrelationships that have been established for impeller-based systems. Tatterson (58) describes a number of elementary scale-up procedures for agitated tank systems that depend upon operational similarity. Thus, when scaling up from levels 1 to 2,... 

Experimental work has not validated the scaling procedure above with respect to scale-up of blending processes. Since this approach also relies on empirical work, this model should not be favored over other approaches currently in use, though it may provide additional insights. 

Scale-up is generally defined as the process of increasing batch size. Scale-up of a process can also be viewed as a procedure for applying the same process to different output volumes. There is a subtle difference between these two definitions batch size enlargement does not always translate into a size increase of the processing volume. 

Although the scale-up of agitated vessels is mainly based on geometrical similarity, there are various cases where this target is difficult to achieve. Furthermore, the application of geometrical similarity does not ensure the similarity of dynamic and kinematic phenomena. Experience and intuition have to be employed in the scale-up procedure (McCabe et al., 1983). 

---