(189j) Temperature Mapping of Pharmaceutical Trickle Bed Reactor for Continuous Hydrogenation

Authors: 
Sheng, H., Pfizer
Pfisterer, D., Pfizer
Ljubicic, T., Pfizer
Hawkins, J. M., Pfizer Inc.
Mustakis, J., Pfizer Inc.
Diaz, A., Pfizer
Temperature Mapping of Pharmaceutical Trickle Bed Reactor for Continuous Hydrogenation

Huibo Sheng, Tomislav A. Ljubicic, Angel R. Diaz, David Pfisterer, Joel M. Hawkins and Jason Mustakis, Pfizer Global Research & Development, Pfizer Inc., Groton, CT

Trickle bed reactors (TBRs) are fixed bed reactors that widely used in chemical and petroleum industries for gas-liquid-solid three-phase reactions1 and they have been extensively studied under the conditions for these industrial applications on large scale.2 Pharmaceutical applications are on a much smaller scale, and the general flow dynamics together with the multiphase interactions can be very different. Therefore, an online monitoring method is highly desired in the development of pharmaceutical TBRs for continuous processes. Axial temperature distribution of trickle bed reactors is of great interest as it directly indicates the status of many pharmaceutical reactions such as hydrogenation of active pharmaceutical ingredients (APIs). The profile is also of great importance to a safe operation of trickle bed reactors to prevent the formation of local hot-spot that may lead to catalyst deactivation or reaction failure.3

Traditionally, a set of thermocouples are typically used to measure the axial temperature along the reactor.4 This method, however, can only provide with very limited and location dependant temperature data. Recently, NMR imaging technique has been developed for temperature mapping of lab-scale fixed-bed reactor.5, 6 However, this technique requires calibrating the chemical shifting at different temperatures. Thus, it is by nature chemical compound dependent as any catalyst or chemical change will require a re-evaluation of whether it is still applicable or a re-correlation of chemical shifting-temperature relationship. In this work, an optic fiber temperature sensor is employed to measure the axial temperature distribution of benzyl alcohol hydrogenation as a model reaction. Along with the different temperature profiles, the TBR operation associated catalyst activation, deactivation, and regeneration are also discussed. This advanced technology enables real time axial temperature profile monitoring of trickle bed reactors from lab to large-scale and can be applied to any reaction systems.

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