Charline Berguerand

Life cycle analysis within pharmaceutical process optimization and intensification: case study of active pharmaceutical ingredient production.

As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities.

Intensification of slow reversible chemical transformation: carboxylation of resorcinol as a case study

Abstract Conjugated kinetic and thermodynamic modeling is suggested as a suitable approach to identify a novel process window (NPW) for the intensification of slow reversible reactions. The aqueous Kolbe-Schmitt synthesis of β-resorcylic acid is taken as a model. The potential of operating at high pressure (P) and temperature (T) is evaluated in order to reduce the characteristic reaction time (tr) and increase the specific productivity. For the first time, a reliable kinetic model for this reaction is derived from batch experiments. Based on this model, an NPW of P=10 bars, T=453 K is determined for a continuous reactor operated at a residence time of 28 s. It is predicted that the specific productivity can be increased by a factor of 100 with a 4.2 times less concentrated KHCO3 solution, as compared to a conventional batch process, if the reaction is kinetically controlled. The model prediction is experimentally validated with a continuously operated milli-reactor equipped by SMXS mixer elements (Sulzer Chemtech, Switzerland) ensuring a fast mixing (characteristic mixing time ~4.10-2 s). The milli-reactor renders exclusively β-resorcylic acid (selectivity 100%) and confirms process intensification (PI) of two orders of magnitude as compared to conventional batch operation.