Page 231 - Chiral Separation Techniques

8.4 Operating Aspects of Nonchromatographic Separation Systems 209

umn, selective for the S enantiomer. The eluate (strip solution) from this column is
rich in S (80 % S,20% R). The relatively concentrated eluate is either changed in
pH or solvent diluted to become similar to the pH and/or solvent of the original feed
and then passed through ChiraLig™ R-1 and R-2 columns for further purification
and enantiomer removal. The resulting stream from the third stage contains 98.46 %
S enantiomer. A subsequent concentration and purification step is performed (if
needed) at this stage by using a ChiraLig™-S column for extra purity or a different
nonselective concentration column. The resulting eluted product is both optically
(98.46 or 99.7 % depending on whether an extra concentration stage is included and
whether ChiraLig™ is used) and chemically pure. The overall separation is efficient,
minimizes the use of solvent, and is capable of producing a high-purity chiral prod-
uct.
The raffinate from the ChiraLig™-S-1 column is rich in R, but still contains some
(20 %) S enantiomer. This serves as the feed into the ChiraLig™-S-2 column fol-
lowed by the ChiraLig™-S-3 column for final raffinate containing 98.46 % R. The
eluents from the S-2 and S-3 columns are solvent or pH adjusted for recycle back
into the system, so that an overall loss of S isomer of only ≈ 1.5 % occurs. The sep-
arations process uses the molecular recognition matrix to achieve 98.5 % purity of
the S isomer in three stages. It also allows for potential isomerization of the 98.5 %
R-isomer for recycle and ultimate conversion to the S-isomer. Increased α values
above 4, as assumed of the 98.5 % R-isomer in this illustration, lead to higher puri-
ties and/or reduced separation stage requirements as described earlier.

8.4 Operating Aspects of Nonchromatographic Separation
Systems

For an industrial-scale separation, operating and capital costs for a separations tech-
nology are critical parameters, and can make the difference between acceptance or
ultimate rejection of a technology. These considerations are especially important in
the pharmaceutical industry, where production costs must be minimized over the
lifetime of the patent. When the drug comes off patent, production costs are even
more important because the drug company must compete with other producers, and
the drug price point drops. A gain in production efficiency from a superior separa-
tions process represents an additional source of competitive advantage to the drug
company.
When investigating the suitability of a particular resin-bound separations process,
the following factors are often important: (i) resin consumption; (ii) solvent usage;
(iii) productivity–chemical, optical and volume yields; (iv) total number of separa-
tions steps; and (v) capital costs. For any particular process, these factors differ in
their relative importance. However, when evaluating a new separations method it is
useful to examine each of these factors. The nonchromatographic separation method