Scale-up and pilot plants

Engineering Aspects of Process Scale-Up and Pilot Plant Design... 

The development model presented here may differ from some formulation research programs in that biostudies may not be performed on small-scale batches. The major advantage of early biostudies is the potential for early IVIVC and subsequent surrogate use of dissolution testing in further work. Scale-up and pilot-plant roles in formulation changes, while not covered thoroughly here, are reviewed by Racz. ... 

Chemical reaction hazard identification involves consideration of several points during the process scale-up and pilot plant stages ... 

Oldshue [57] reviewed the basic principles of fluid mixing of cosmetic formulations, presenting the General Mixing Theory, the applications to liquid-liquid, liquid-solid, and gas-liquid systems, scale-up, and pilot planting considerations. 

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

In this chapter, we consider nonideal flow, as distinct from ideal flow (Chapter 13), of which BMF, PF, and LF are examples. By its nature, nonideal flow cannot be described exactly, but the statistical methods introduced in Chapter 13, particularly for residence time distribution (RTD), provide useful approximations both to characterize the flow and ultimately to help assess the performance of a reactor. We focus on the former here, and defer the latter to Chapter 20. However, even at this stage, it is important to realize that ignorance of the details of nonideal flow and inability to predict accurately its effect on reactor performance are major reasons for having to do physical scale-up (bench —> pilot plant - semi-works -> commercial scale) in the design of a new reactor. This is in contrast to most other types of process equipment. 

Experience in solvent extraction processes has shown that such processes can be scaled up from pilot plant—or even bench-scale—data quite reliably. This is particularly evident in processes employing mixer-settlers. However, scale-up will only be as reliable as the data on which it is based, and time spent in obtaining the correct and relevant data will always pay dividends. 

As a reason for not using h.v.t. it is often stated that its use leads to experimental results that cannot be reproduced on an industrial scale. This is untrue. A closed system, such as an all-glass vacuum line, has more in common with an industrial plant than the typical apparatus used at the laboratory bench. Furthermore, because of the considerably more favourable surface to volume ratios in a large plant, the typical concentrations of those impurities which originate from surfaces are more accurately reproduced by h.v.t. experiments than by the typical bench experiment. This is often reflected in the problems encountered during development work when bench experiments are being scaled up to pilot plant and beyond. 

The process has been successfully scaled-up to pilot plant level and the product characteristics are yield > 98%, purity 95-99% and particle size 40-60 pm. At the same time, this process reduces the environmental impact of TATB production as compared with the traditional TCB Route [52]. 

Laboratory units can be divided into bench-scale, research-, and pilot-scale. Bench-scale units, available in sizes of 20 to 500 ml (up to 400 bar) are used for screening tests, because one can obtain a relatively fast overview of the influence of the diverse major parameters, and only small quantities of raw material are necessary. Optimization duties require research units in sizes of 2 to 10 1, and are available in the pressure range between 325 and 700 (1000) bar. Such units enable quantity- and quality analyses. An illustration of one commercially available unit is shown in Fig. 8.1-1. For scale-up purposes, pilot plants ranging from 20 to 100 1, with design pressures up to 550 (700) bar, are recommendable for use with new products. 

Description of the logic behind all pertinent activities that occurred during scale-up, from pilot plant production to phase 3 clinical production. Discuss problems, failures, and so on. Justify the absence of equivalency concerns despite differences in process parameters, equipment, facilities, and systems. Description of the logic behind all pertinent activities that occurred during technology transfer from phase 3 clinical... 

Other work has been mainly concerned with the scale-up to pilot plant or full-scale installations. For example, Beltran et al. [225] studied the scale-up of the ozonation of industrial wastewaters from alcohol distilleries and tomato-processing plants. They used kinetic data obtained in small laboratory bubble columns to predict the COD reduction that could be reached during ozonation in a geometrically similar pilot bubble column. In the kinetic model, assumptions were made about the flow characteristics of the gas phase through the column. From the solution of mass balance equations of the main species in the process (ozone in gas and water and pollution characterized by COD) calculated results of COD and ozone concentrations were determined and compared to the corresponding experimental values. 

In some practical kinds of dryers, the flow patterns of gas and solid are so complex that the kind of rate equation discussed in this section cannot be applied readily. The sizing of such equipment is essentially a scale-up of pilot plant tests in similar equipment. Some manufacturers make such test equipment available. The tests may establish the residence time and the terminal conditions of the gas and solid. 

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