Integral resource management by exergy analysis for the selection of a separation process in the pharmaceutical industry

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Abstract
This paper reports a detailed analysis of the resource intake necessary for the separation of a mixture of diastereoisomers (2R,3R)-3-(3-methoxyphenyl)-N,N-2-trimethylpentanamine 6 and (2R,3S)-3-(3-methoxyphenyl)-N,N-2-trimethylpentanamine 7 in the production of an active pharmaceutical ingredient. The resource intake analysis is based on exergy calculations of both material (chemicals) and energy (utilities) requirements. For two separation processes, crystallisation and preparative chromatography, analysis is not only carried out at the process level (α level), but also at the plant level (β level) taking into account the 6 preceeding synthesis steps towards the diastereoisomers and the supporting processes, e.g. for delivering heating media from natural gas or treating waste gases. Finally, exergetic life cycle analysis allowed the inclusion of the overall industrial metabolism (γ level) that is required to deliver all energy and materials to the plant to carry out the separation. The results show that, in this example, the large scale chromatography process is not the most resource efficient option because of its high utilities requirement, despite its lower chemical requirement (180 MJ versus 122 MJ total requirement per mol of the RR stereoisomer (2R,3R)-3-(3-methoxyphenyl)-N,N-2-trimethylpentanamine monohydrochloride 8) (α level). Due to its higher efficiency, the plant only requires 4.6% more resources when it selects chromatography instead of crystallisation (434 versus 415 MJ total requirement per mol of the RR stereoisomer 8) (β level). Since the efficiencies of the overall industry depend on the type of materials and energy that it has to deliver to the plant, overall resource withdrawal from the environment differs by 4.2% for crystallisation and chromatography (883.7 and 920.6 MJ mol−1 stereoisomer 8). The study has also shown that resource efficiency gain can be achieved by recycling solvents on the plant. Moreover, it is clear that there is more potential for resource efficiency improvement for the crystallisation than for chromatography because of the different nature of the resources consumed: chemicals, including solvents, versus utilities.