Micromixers based process

A yield of 95% was obtained by a micromixer-based process (<10s, at —10°C), whereas the industrial batch process (6 m stirred vessel) had only 72% yield (5 h, at —20 °C) [68]. The lab-scale batch process (0.51 flask 0.5 h, at —40 °C) had 88% yield (see Table 9.4). Pilot-scale studies followed with a homebuilt minimixer for reasons of clogging, which was not decisive at the lab scale. With one minimixer at the pilot scale, a yield of 92% was obtained (<10s, at — 10°C). The validity of the numbering-up concept was proven by operating also five minimixers of the same type at a yield of 92% (< 10 s, at —10 °C). This was the central part of the actual production process, running for more than 3 years until the life cycle of the commercial product of the corresponding multistage process run out (see Figure 9.34). 

In contrast, solid lipid microparticles consisting of a tripalmitin matrix and cationic lipids prepared using the micromixer-based solvent extraction process as described by Emi et al. [50] were of monomodal size, showing a narrow size distribution in the submicrometer range (Table 8.1). 

In the chemical industry (on the mega- as well as the micro-scale) fine emulsions have many useful applications in, e.g., extraction processes or phase transfer catalysis. Additionally, they are of interest for the pharmaceutical and cosmetic industry for the preparation of creams and ointments. Micromixers based on the principle of multilamination have been found to be particularly suitable for the generation of emulsions with narrow size distributions [33]. Haverkamp et al. showed the use of micromixers for the production of fine emulsions with well-defined droplet diameters for dermal applications [38]. Bayer et al. [39] reported on a study of silicon oil and water emulsion in micromixers and compared the results with those obtained in a stirred tank. They found similar droplet size distributions for both systems. However, the specific energy required to achieve a certain Sauter mean diameter was 3-1 Ox larger for the macrotool at diameters exceeding 100 pm. In addition, the micromixer was able to produce distributions with a mean as low as 3 pm, whereas the turbine stirrer ended up with around 30 pm. Based on energy considerations, the intensification factor for the microstirrer appears to be 3-10. 

Improved properties of the azo pigment Yellow 12 were also achieved in a micromixer-based azo coupling process (Scheme 4.20), providing a smaller pigment size distribution [42]. Compared with the corresponding commercially available standard, the glossiness of Yellow 12 was increased by 73% and the transparency by 66% while maintaining the tinctorial power. 

The conventional scale-up criteria scale-up with constant stirrer speed , scale-up with constant tip speed and scale-up with constant specific energy input are all based on the assumption that only one mixing process is limiting. If, for example, the specific energy input is kept constant with scale-up, the same micromixing behaviour could be expected on different scales. The mesomixing time, however, will change with scale-up as a result, the kinetic rates and particle properties will be different and scale-up will fail. 

In order to account for both micromixing and mesomixing effects, a mixing model for precipitation based on the SFM has been developed and applied to continuous and semibatch precipitation. Establishing a network of ideally macromixed reactors if macromixing plays a dominant role can extend the model. The methodology of how to scale up a precipitation process is depicted in Figure 8.8. 

Process models based on the convective diffusion equation have an inherent level of micromixing. Examples of such models include laminar flow with or without radial diffusion and the axial dispersion model. The models can be used to predict a RTD. With that distribution comes a specific extent of micromixing, and the model contains no adjustable parameter to vary the extent of micromixing that does not also vary the RTD. Predictions from such models are used directly without explicit concern for micromixing. The RTD corresponding to the models could be associated with a range of micromixing, but this would be inconsistent with the physical model. 

Numerous micromixers have been designed based on the prindple of laminar static mixers, where the fluid undergoes a periodic process of splitting, rotation and recombining. These mixers are inspired by chaotic mixing, where the geometry of the system imposes spatial periodicity. 

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