**1.1 Highlights**


• Validation of these reactors using well know reaction system and listing out advantages of flow over batch processes.

Continuous production techniques have been used by the chemical industry for a long time, but it is only recently that flow equipment has become available for the use of the laboratory scale, especially in the pharmaceutical industry. This means that flow processes established in the lab could be readily transferred to the production facilities and scaled for commercial use, without substantially altering the reaction conditions [1– 3]. The flow processes are gaining high visibility across pharmaceutical industries for varied reasons [4]. One reason could be predominately the economics of running the batch processes verses the flow process. At the onset, the flow processes are well established in the manufacturing of commodity chemicals, meanwhile, the batch processes are highly acquainted in the pharmaceutical industries. In the advent, the flow processes offer wide advantages such as effective heat and mass transfer, superior inherent safety, flexibility, reproducibility, energy efficiency, high reactor throughput, fast and effective mixing, low footprint, in-line automation, and low operating cost [5].

Flow processing has demonstrated chemical production safer, more reproducible, and scalable while offering reduced cost and low environmental impact. Flow processes are more energy-efficient, with precise control over reaction conditions leading to less waste and environmental impact and serving green chemistry principles [6].

By way of example, for every kilogram of a fine chemical produced by the pharmaceutical industry, 5–100 times that amount of chemical waste is being generated [7]. This unacceptable inefficiency with the present state-of-the-art, large scale batch production of chemicals is driving the adoption of resource-efficient flow chemistry alternatives as innovative solutions for chemical manufacturing.

Developments are at a high pace in transforming the batch chemistries to flow processes at the academic level and there is a quite demand building up across industries. In recent years, flow chemistry has become a viable alternative to traditional batch chemistry, with a six-fold increase [6] in the publications featuring micro and meso reactors. The literature which supports the transformations was more in running the experiments without the engineering concepts being discussed such as kinetics, mixing, dispersion, and residence time distributions. On the other side, there have been numerous companies launching flow process development skids for quick and easy development strategies without insight on the reaction or its suitability. An effort towards understanding these concepts become decisive.

Flow reactors for continuous flow processing are typically tubular, packed bed, or microfluidic chip-based systems, where reagents are introduced at different points into the tube in a continuous stream [8]. Because of the small dimension of the tubes and built-in automation, well-defined temperature, pressure, and reaction times are achieved thereby achieving desired product profiles. Initial capital outlay is reduced, compared to traditional batch reactors, and scale-ups could be achieved by running identical parallel channels, making flow chemistry a viable manufacturing approach for small and niche manufacturers.

The characterization of the reactor such as flow patterns becomes essential to decide the performance of these reactor types. There are specific methods available in the literature to characterize the flow reactors, whether it is plug flow, CSTR (Continuous stirred tank reactors), fluidized bed reactor, or packed bed reactor [9–11]. Generally, there is two class of reactors, which are completely mixed or completely plug flow reactors. The residence time distribution (RTD) studies [12–15] were performed to characterize [16–19] the reactor types and to estimate the deviation

from the ideal behavior of the reactor under the flow conditions. All the real reactors fall, somewhere between mixed and plug flow [12, 20], the reason could be due to stagnation, recycling of the fluid, channeling of fluid, the difference in the temperature, inadequate mixing with the reactant streams and axial dispersion patterns [13].

As a first approximation, one could establish a model around each reactor to prove the performance using the characteristic information defined in the literature [21]. In the real scenario, we could realize the ineffective contacting, mixing, and lowering in the performance than the ideal case [18, 22]. The RTD is characteristic information to estimate the degree of mixing and opportunities to improve the same through the design of the reactor [12]. Nevertheless, the RTD studies provide significant information around the gaps and opportunities to improve the process from an equipment perspective [22–24]. In general, the shortfalls could be around the channeling, recycling of the fluid, stagnation, and dead zones within the reactor [9].

Various dimensionless parameters were discussed in the literature to support the studies and to develop correlation to understand the performance behavior of these reactors [22, 25–27].

In the present study, customized plug flow and packed bed reactors were designed and fabricated on an appropriate scale. The reactors were characterized through detailed RTD studies. The characteristic plots are used to estimate the behavior of the flow reactor. Well-studied saponification of ethyl acetate in the presence of sodium hydroxide was considered for validating these reactors and demonstrating the advantages of flow processes over the batch process. The hydrolysis of ethyl acetate was essentially an irreversible second-order reaction, in which the sodium acetate and ethyl alcohol were formed as products. In the literature, the emphasis was given to reaction kinetics and mechanism of the reaction than process intensification using various reactor types and their importance. The information around detailed process intensification studies is very nominal and not available in the open literature to the best of authors' knowledge.
