Microstructured Reactors for Rapid Process Development and Scale-Up - Pharmaceutical Technology

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Microstructured Reactors for Rapid Process Development and Scale-Up
The authors discuss a continuous-flow reactor that avoids parallel channels and enables economic plant setup. This article is part of a special issue on API Development, Formulation, Synthesis and Manufacturing.

Pharmaceutical Technology
pp. s32-s36

Equipment design for single-channel microreactors

Lonza designed a small, compact plate device called the LabPlate reactor to visualize the flow inside the microstructured channel. The device enables personnel to design reactor channels and develop processes with low flow rates when reagent availability is limited. Process conditions are similar to those in capillary chemistry, as well as in larger reactor devices, with the advantage that the reaction zone can be inspected and viewed. Multiphase reactions can be observed with phase distribution, as can the precipitation of metastable intermediates.

Figure 1: (Left) A LabPlate reactor (Lonza, Basel) with microstructured channels and thermal fluid and reagent connections. (Top right) A typical mixing channel with nozzle-type contacting element and tangential mixing elements. (Bottom right) A single mixing channel during a gas–liquid test reaction in the LabPlate microreactor. (IMAGE IS COURTESY OF LONZA)
The fluid entering the microchannel within the reactor plate passes through the entrance, contacting element, and several mixing- and residence-channel elements, each with its own design (see Figure 1). The entire LabPlate reactor consists of a cooling block with cover plate, microstructured plate, view glass, and flange housing (see Figure 2). The fluids are sealed against the external environment by conventional O-rings; the reagents and heat-exchange medium are separated by metal walls. The modular setup allows the integration of several microstructured plates, as well as the integration of the reactor into other flow equipment. The entire device can be integrated into a modular microreactor system (MMRS, Ehrfeld Mikrotechnik BTS, Wendelsheim, Germany) (7).

Figure 2: A microreactor (LabPlate, Lonza, Basel) for development purposes, including a microstructured plate with heat-exchange block and connections for the heat-exchange medium (left) and a typical plate-stack reactor setup with A6 or A5 size (right). (IMAGE IS COURTESY OF LONZA)
Lonza developed a plate stack reactor for reactions that typically take minutes to complete (see Figure 2) (8). The reactor is based on the multiscale approach, which adapts plates of various sizes to the reaction needs. For example, operators may use a tiny channel at the start of the reaction, when heat generation is strong, and gradually increase the size of the plates to accommodate slower reaction rates (i.e., less heat evolution). This design optimizes heat transfer, minimizes pressure drop, and greatly increases volume (i.e., by as much as several mL). In addition, the reactor may be combined with conventional heat exchangers and tube equipment to gain several liters of volume and several minutes of residence time. Lonza manufactures and distributes the reactor in cooperation with Ehrfeld Mikrotechnik BTS (7).

The microstructured reactor plates are made from corrosion-resistant material and can perform various tasks in a modular setup. Plates are designed for mixing and heat exchange. Mixing plates include a mixing channel as well as wider channel elements to provide sufficient reactor volume for heat exchange and appropriate residence time. In an effort to standardize Lonza's proprietary MicroReactor design, the company chose production-plate sizes based on the European A4, A5, and A6 standard paper sizes. Each size features a plate area double that of the previous size, thus doubling the heat-exchange area and reactor volume. The sizes enable scale-up, which is related to the reaction's kinetics (9). Thus, for rapid reactions with typical reaction times of less than 1 s (i.e., mixing controlled, Type A), the aims are the following:

  • To ensure sufficient cooling between the reactor plates and mixing channel
  • To provide short mixing times in tiny, complex channels with a comparable high-pressure drop.

For rapid reactions with typical reaction time between several seconds and 10 min. (i.e., kinetically controlled, Type B), the aims are the following:

  • To maintain volume for sufficient residence time for the reaction and the same area-to-volume ratio for enhanced heat transfer
  • To optimize mixing quality by choosing a pressure drop as low as possible.


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