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20 August / September 2016


first 10 injections at 2 seconds, followed by 5 injections at 10 seconds and a further 5 at 20 seconds duration. The early eluting components diminished in concentration within the first 4 to 8 injections whereas the more retained (and presumably more polar) constituents maintained an appreciable concentration in the extracts even after 20 injections. This presumably follows the


Figure 9. Production chromatogram 10 injections. 2 second injection, 3 minutes re-equilibration between injections, detection at 250 nm. Other conditions as experimental


solubility of these components in pure CO2 and perhaps a low diffusion rate of these components from the matrix. This is in contrast to the rapid elution of the warfarin components, perhaps because these were coated in an approximately monomolecular layer on the surface of the support (calculated from the relative surface areas of the support and the warfarin molecule and its concentration) rather than located within a complex organic matrix.


While the peak areas of the major component (eugenol) are difficult to measure due to the high mass overload, it is clear that this component, despite a good solubility in the supercritical CO2


, is not


rapidly extracted but appears to follow the normal Overall Extraction Curve format for extraction with a rapid initial extraction rate falling to a diffusion-controlled process as the extraction continues. It is possible that the rather large particle size of the ground cloves contributed to the slow reduction in concentrations of the less-soluble components and further experiments using smaller particle sizes and extraction solvents containing a polar co-solvent to enhance the solubility are planned.


Figure 10. Minor component area at 230 nm vs injection #. Runs 1 – 10: 2 second injection time; runs 11 – 15: 10 seconds, 16 – 20: 20 seconds. See key for peak retention times.


Figure 8 show the differences in the results. Additional material was extracted at the higher pressure as would be expected. While integration of the overloaded and overlapped peaks is not accurate, it is possible to estimate the increase in quantity extracted from several of the minor components that are a little better resolved than the others. On this basis, one can estimate a 1.85-fold increase in extracted material resulting from the 50 bar increase in pressure. At the same time, the increase in operating pressure also changed the selectivity of the separation with a decrease in retention and some loss in resolution between several of the components.


A production experiment, making multiple injections to follow the trajectory of minor component concentrations was carried out


under the same conditions with a 2 second injection period and 100 bar back pressure. In contrast to the experiment with warfarin, the injection volume here was less than the extractor volume of around 6 ml. Since in the case of warfarin the minor components were eluted in the first two injections, it would be expected that between three and six injections would be necessary here to achieve the same result. The chromatogram (at 250 nm) of the first ten injections is shown in Figure 9. While some early eluting components diminished in concentration over the first 4 or 5 injections, concentrations of many of the later eluting components were reduced by a much smaller factor. A plot of minor component peak areas (at 230 nm) against injection number is shown in Figure 10. This includes data taken for the


The products from this experiment and another using 10.7 g of ground cloves in an extractor 50 x 21.2 mm were collected. Analysis of one of the products is shown in Figure 11. No impurities could be detected in the product fractions from these and from an experiment using conventional injection of 68 mg of commercial clove oil under the same separation conditions. The recovery of eugenol from the clove oil was calculated to be 92%; the content of eugenol in the cloves used in the two extraction experiments was calculated to be 7.22% and 7.75% respectively for the two extractions.


Conclusions


The results of the work described in this paper show that extraction-injection techniques in preparative SFC can allow a very rapid isolation and purification of impurities in a sample by selectively extracting them into a purification column. Rather than spending a long time in injecting a solution of the product


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