Materials and methods

2.1 Eco-efficiency measuring methods (EEMMs)

For the evaluation of the eco-efficiency of both pharmaceutical production processes (batch vs. continuous), different EEMMs will be used. It is the purpose to calculate the eco-efficiency by using a wide range of different EEMMs and evaluate these results. Using this set of EEMMs will allow better understanding of the principles and possibilities of the EEMMs under consideration. This will contribute to the EEMM inventory to be made during the Eco2chem project and finally resulting in the Eco2chem EEMM decision tool. The specific EEMMs used for this comparison (batch vs. continuous pharmaceutical production step) will be the E-factor, ETH's Finechem tool, exergy analysis at the process and the plant level, Cumulative Exergy Extracted from the Natural Environment (CEENE) method, carbon footprint (IPCC 2007 - GWP), Eco-indicator '99, ecological footprint and the cumulative energy demand (CED) [2-4, 7-10]. More information on EEMMs can be found in the references.

2.2 Pharmaceutical production processes: batch versus continuous production

The case supplied by Janssen Pharmaceutica is the comparison of two alternatives for the sixth production step in the galantamine (anti-Alzheimer medication) production route. This sixth production step originally is a batch based production step, but can be replaced by a continuous production step using a micro reactor. In Figs. 1 and 2, an overview is given of the eight steps required

The case supplied by Janssen Pharmaceutica is the comparison of two alternatives for the sixth production step in the galantamine (anti-Alzheimer medication) production route. This sixth production step originally is a batch based production step, but can be replaced by a continuous production step using a micro reactor. In Figs. 1 and 2, an overview is given of the eight steps required

Figure 1:

Synthesis route for the production of 1 mol intermediate H using the batch process in step 6.

Figure 1:

Synthesis route for the production of 1 mol intermediate H using the batch process in step 6.

chktrabenizene

Step 1

m

Brominatlcn

yield - 87 5%

Step 2 Qemethylatlon HjSOj [n water yield = 32%

9.6 muí Start product

Step 2 Qemethylatlon HjSOj [n water yield = 32%

w

Step 3

Inline formation,

reduction

H lid fumiylation

yield b 59.5 %

Ring cEnsnrn in chtoro-benzene yield - 45 %

7.6 mol Amine

Ring cEnsnrn in chtoro-benzene yield - 45 %

Step 5 chlorot>enzene reuytdlny and crystal Illation yield - 85 %

Step 8 enantle-sepai aiion yield = A4,5%

Step 7 debrominalion yield - 75 %

Step 5 CÜN1INUOUS meïhylalion yield = BB%

Figure 2:

Synthesis route for the production of 1 mol intermediate H using the continuous process (micro reactor technology) in step 6.

for the production of 1 mol of the galantamine intermediate H. The evaluation by the different EEMMs is not limited to production step 6 but also shows the impact of taking into account the other steps of a pharmaceutical synthesis route. In Figs. 1 and 2, the improvement of the yield and its impact on the other production steps is illustrated.

The total data inventory required for the calculation of the used EEMMs, including all the mass and energy balances of all eight production steps is not given due to confidentiality issues and the overload of information.

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