Continuous pharmaceutical production

The aims of this research field are to support the substitution of existing batch production lines in pharmaceutical companies with small continuous mini-reactors and unit operations.

Traditionally, production of active pharmaceutical ingredients (APIs) has been conducted in batch reactors. Advantages of this production form are relatively easy upscaling from laboratory to full-scale reactors, flexible process equipment, controlled batch numbering of the chemical product, and minimal automated process control. However, disadvantages are that the reactors are energetically inefficient (large reactor volumes), pose a larger safety threat due to the reactor size, are labor intensive, and may cause more byproduct to be produced because reaction conditions are hard to control in a large volume.

In recent years, continuous production of APIs has received more interest. Advantages of continuous production are higher yields, utility reduction because heating/cooling and reflux streams are handled more efficiently, more homogeneous reaction conditions, reduced costs of equipment and implementation, fewer safety issues (smaller reactors, lower hold up), easy cleaning, and reduction in labor costs and physical space savings. 

Research

Converting a batch production into a continuous operation mode requires a detailed quantitative understanding of the chemical reactions involved. The choice of reactors and separation equipment to use in a given case depends on the number and type of side reactions taking place, the phases involved, reactant and product solubilities, and the rates of the chemical reactions. The aim is to use mini (liter size) reactors as opposed to large (m3 size) batch reactors so that the production can simply go on during normal working hours, be safe, and take up little space. Novel reactor designs must be developed, not for every single reaction, but for each type of reaction, ideally to reach a state of “plug-and-play”, where standard continuous equipment is selected when a new synthesis route is to be established.

Our philosophy is to work on all relevant reactor and unit operation designs and we have carried out fundamental and applied research on, for example, the following topics: 

  • Design and operation of a mini filter reactor for continuous production of a selected pharmaceutical intermediate
  • Upscaling and implementing a mini filter reactor in a pharmaceutical company
  • Design and development of continuous unit operations

We are presently active with:

  • Continuous crystallization equipment

  • Continuous reactors for Grignard reactions in general

  • Continuous reactors for slow organic chemical reactions

Contact

Kim Dam-Johansen
Professor, Head of Department
DTU Chemical Engineering
+4545 25 28 45

Contact

Søren Kiil
Associate Professor
DTU Chemical Engineering
+4545 25 28 27