New Scale-Up Technologies for Hydrogenation Reactions in Multipurpose Pharmaceutical Production Plants

Abstract

The classical scale-up approach for hydrogenation reaction processes usually includes numerous laboratory- and pilot-scale experiments. With a novel scale-up strategy, a significant number of these experiments may be replaced by modern computational simulations in combination with scale-down experiments. With only a few laboratory-scale experiments and information about the production-scale reactor, a chemical process model is developed. This computational model can be used to simulate the production-scale process with a range of different process parameters. Those simulations are then validated by only a few experiments in an advanced scale-down reactor. The scale-down reactor has to be geometrically identical to the corresponding production-scale reactor and should show a similar mass transfer behaviour. Closest similarity in terms of heat transfer behaviour is ensured by a sophisticated 3D-printed heating/cooling finger, offering the same heat exchange area per volume and overall heat-transfer coefficient as in production-scale. The proposed scale-up strategy and the custom-designed scale-down reactor will be tested by proof of concept with model reactions. Those results will be described in a future publication. This project is an excellent example of a collaboration between academia and industry, which was funded by the Aargau Research Fund. The interest of academia is to study and understand all physical and chemical processes involved, whereas industry is interested in generating a robust and simple to use tool to improve scale-up and make reliable predictions.

New Scale-Up Technologies for Multipurpose Pharmaceutical Production Plants: Use Case of a Heterogeneous Hydrogenation Process

“…The detailed design of the SDR is described in a previous article. 1 The final installation is shown in Figure 2. The SDR has a working volume of 1.4 L, resulting in a scale-down factor of approximately 1/2850.…”

“…As an alternative approach, the parameters of the six equations from the literature were optimized to fit the experimental data, similarly to how it was done for the heat transfer model of this vessel. 1 Even with optimized parameters, the equations were not able to describe the measurements with sufficient accuracy. Hence, a new equation that is able to model the mass transfer behavior of our specific vessel was developed.…”

“…To achieve a similar mass transfer, the geometry of the agitator, baffles, and the base were kept similar to the geometry of the production vessel. The detailed design of the SDR is described in a previous article . The final installation is shown in Figure .…”

“…The final dynamic process model includes a heat transfer model and a mass transfer model (Chapter 3.2) of the 4000 L reactor and a kinetic model describing the chemical reactions occurring during the process (Chapter 3.1). These subsections of the model were combined within the scope of a customized Dynochem model, which also takes into account the temperature-dependent physical properties of the liquid phase of the reaction mixture dynamically.…”

“…Modeling, digitalization, and automation have become fundamental tools for process chemists and are now integral components of quality by design strategies, which aim to ensure product quality by designing and controlling manufacturing processes based on an understanding of the product and the process. 1 Experimental techniques combined with mechanistic mathematical models have been effective for homogeneous reactions but have limitations in their application for heterogeneous processes. The first step in overcoming these limitations is to conduct laboratory experiments that closely mimic the large-scale environment of the chemical process.…”