Summary and discussion

148 Design and evaluation of the enantiomer production process

The calculations done in this section clearly show the potential of performing the advantageous production of S-enantiomer (component 1) of both anaesthetics by using higher pressures. This process could be successfully applied when no R-enantiomer is wanted and no high recovery is required. The possibility to collect the pure R-enantiomer would include the separate collection of the mixed fraction that leaves the column at the beginning of the desorption step and then the collection of the remaining pure enantiomer. The investigation of such a concept could be a part of the future work on this topic.

In order to improve the recovery of the products, process with two or more beds could be employed. In that way, while one column is in adsorption step, the others would be in different stages of desorption, pressurization or blowdown. This concept also provides great conservation of energy and separation work.

By comparing the overall performance of the here examined four-step PSA with the GC separation operated by repetitive injections and by taking into account that the PSA process is more complicated, the batch GC is selected as a more suitable process for enantioseparation of the anaesthetic gases.

Design and evaluation of the enantiomer production process 149

1. Process performance of a batch single-column process.

Separation in the batch mode is done by performing repetitive injections, where the end of one peak coincides with the start of the peak from the subsequent injection. The first step in the analysis was to perform volume-overloading tests in order to determine the conditions that would provide highest production of pure enantiomers. It is shown that the process is able to provide high purity (over 99 %) and high productivity of the single components. The recovery for the anaesthetics was in the range 50-70 %, while for bicalutamide the achieved values were over 90 %. The productivity and recovery could be further increased by allowing lower purity and higher flowrates.

2. Scale-up procedure for the batch separation.

To achieve the goal set in this thesis for the anaesthetics, which was to produce at least 1 g of both pure enantiomers in less than 24 h, larger separation columns were introduced.

When the bed length was kept constant, and the diameter was increased from 0.6 cm to 1.66 cm, the time needed for collecting 1 g was reduced from 166 h to 22 h for isoflurane and from 78 h to 11 h for desflurane. These findings served for planning further experiments of the SPP1570 Subproject II.

3. Product capture after the separation.

The production of pure substances cannot be considered complete without providing the way to separate them from the carrier gas (or the solvent for HPLC) and to store them properly. This thesis shows a new capture procedure for anaesthetics (done in collaboration with Subproject II) that directly follows the separation step. Dimensions of three capture columns (characterized by independently measured adsorption isotherms), required for collecting at least 1 g of each pure enantiomer and the mixed fraction, were roughly calculated for the case of desflurane. The obtained values can be used as good estimates for designing future experiments. The capture was described for the batch GC, but the same procedure can be applied for PSA separations.

4. Alternative separation using a PSA process.

In order to evaluate the potential of a continuous separation process of anaesthetic gases, simulation of a four-step one-column PSA was done. After parametric studies, the achieved optimal process performance was compared to the batch separation. It was concluded that this simple PSA configuration can provide higher production of S-enantiomer of both anaesthetics, when the adsorption-step pressure was higher than 605 kPa for isoflurane and 560 kPa for desflurane. However, the recovery values were much lower than in the batch mode. Therefore and due to its simplicity, the batch separation including consecutive injections was selected as more suitable process to separate enantiomers of isoflurane and desflurane.

When performing simulation studies, an important task is to provide experimental validation of the made predictions. By using the experimentally determined elution profiles of the anaesthetics from Subproject II, validation was done first by comparing the values of productivity and recovery resulting from the simulations to those estimated from the

150 Design and evaluation of the enantiomer production process

experimental peaks. The matching was found to be very good. Another validation step was done after implementing the scale-up procedure. According to the applied scale-up rule (eq.

(4.17)) the elution profiles from columns with the same length should be exactly the same.

The experimental peaks originating from three used columns (with the same length and different diameters) were compared and it was concluded that they were indeed very close to each other. These validation tests show not only that the assumptions taken for the scale-up calculations were correct, but also that the usage of the simple model for describing the gas-phase process was justified.

The calculations and experimental validation show that production of pure enantiomers of isoflurane and desflurane is feasible by using the investigated system and that it is possible to collect in just one week, using a laboratory unit, sufficient amounts of the enantiomers that medical doctors need for the first tests of the pharmacological effect of single components.

The further results of the investigation will be presented in the upcoming publications [109, 170].