Exergetic life cycle analysis for the selection of chromatographic separation processes in the pharmaceutical industry: preparative HPLC versus preparative SFC

Abstract

Today, environmentally responsible chemistry is of huge importance in the wake of sustainable production. In the field of the fine chemical and pharmaceutical industry, preparative supercritical fluid chromatography (Prep-SFC) and preparative high performance liquid chromatography (Prep-HPLC) are widely used chiral separation techniques. Prep-SFC is often named as a green alternative for Prep-HPLC without having a thorough assessment of the greenness. However, if metrics are used for process selection with respect to green chemistry, they mainly show three shortcomings: (1) a narrow system boundary approach is used; (2) energy requirements are barely taken into account and (3) if energy requirements are considered, there is a differentiation in mass and energy inputs. Taking into account these shortcomings, Prep-HPLC and Prep-SFC are now compared and evaluated for their integral resource consumption. The evaluation is performed on a specific enantiomeric separation using exergetic life cycle analysis within enlarging system boundaries α, β and γ. Within the α system boundary (process level), Prep-HPLC requires 26.3% more resources quantified in exergy than the Prep-SFC separation due to its inherent higher use of organic solvents. Within the β system boundary (plant level), Prep-HPLC requires 29.1% more resources quantified in exergy than Prep-SFC. However, the Cumulative Exergy Extracted from the Natural Environment (CEENE) to deliver all mass and energy flows to the α and β system boundary via the overall industrial metabolism shows that Prep-SFC requires 34.3% more resources than Prep-HPLC. The poor score of Prep-SFC in the γ system boundary is attributed to the high CEENE value related to the production of liquid carbon dioxide and the use of electricity for heating and cooling. It can be concluded that for this case, the most sustainable process as for the integral resource consumption is Prep-HPLC, unlike the general perception that Prep-SFC outperforms Prep-HPLC.