(126a) Development of a Continuous Hydrogenation Process for Pharmaceuticals Using a Trickle Bed Reactor

Manjrekar, O., AbbVie
Sharma, K., Massachusetts Institute of Technology
Diwan, M., AbbVie
Kotecki, B., AbbVie
Harper, K., AbbVie
Verma, A. A., AbbVie Inc.
Franczyk, T., AbbVie
Chaaya, E., AbbVie
In past decade there has been significant interest in the development of continuous processes in the pharmaceutical industry. Key drivers for continuous processing is product quality improvement, yield and process robustness, footprint reduction of processing area and increased process safety. Hydrogenations are commonly used in synthesis of pharmaceutical intermediates and active pharmaceutical ingredients. In the present work we have demonstrated:

  • Application of a laboratory scale trickle bed reactor for development and scale-up of a continuous hydrogenation process.
  • Detailed description of catalyst packing procedures and startup of trickle bed reactors.
  • Nitro to amine reduction for a pharmaceutical intermediate using a trickle bed reactor.
  • The effect of operating parameters such as pressure, gas to liquid ratio, temperature catalyst loading and residence time of the substrate on product quality, is studied to develop a scalable and robust process.
  • Development of a reactor scale kinetic model to predict conversion in the nitro-amine reduction group.

‘Fit for purpose’ model developed was very effective to efficiently identify optimal reaction conditions, assess risk to product CQAs, and increase overall robustness. The evaluation of these parameters led to a multi-faceted model capable of efficiently identifying optimal reaction conditions, assess risk to product quality attributes and increase robustness of the process.


All authors are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.