Page 238 - Chiral Separation Techniques

216 8 Nonchromatographic Solid-Phase Purification of Enantiomers

each cyclic use, and the corresponding expected high enantiomer throughout can
thus be obtained.

8.6 Areas of Potential Industrial and Analytical Interest for
Nonchromatographic Chiral Separations

Due to the benefits achieved, there are a significant number of applications areas for
the chiral separations technology. Applications in the pharmaceutical industry the in
three main areas: (i) analysis; (ii) drug development; and (iii) commercial produc-
tion. In this industry, the need for chiral separations is to aid in each phase of the
development process from discovery through preclinical and clinical development,
and product launch. In the drug discovery process, the ultimate goal is the identifi-
cation of a single compound for development. During this stage, extensive screening
of available compounds is performed, along with animal testing. Small quantities of
optically pure drug are needed at this stage for preliminary and advanced testing.
Rapid turnaround time is required in order to screen candidate compounds quickly.
The chiral separations phase should be readily synthesized and be relatively versa-
tile in its ability to separate compounds from a class of drugs. For analysis of enan-
tiomers, matrix versatility and rapid throughput are essential. The nonchromato-
graphic matrices were shown to be very versatile and capable of separating a variety
of chiral analytes in a wide range of solvents.
During the preclinical and clinical development stages, the requirements for opti-
cally pure drug quantity increases dramatically, from several grams to 10–100 kg.
The drug is needed for animal studies (pharmacokinetics, metabolism, tissue distri-
bution, and safety), and for human clinical studies in Phases I, II and III. Time is crit-
ical during this stage, and adequate supply of the separations resin must be available
for production of the drug. During this phase, the purifications technology should
exhibit high productivity, as kilogram quantities need to be produced in a short time
period.
During product launch and steady-state production, the purifications goal is to
treat large amounts of racemate (> 25 tons per year) with total process costs well
under the targeted kg drug product price. Moreover, the purifications process must
be robust and easy to operate.
The use of nonchromatographic ChiraLig™ separations technology provides flex-
ibility for rapid separation and throughput of the small quantities of drug (10–100
kg) needed for the early phases of drug development. This technology also provides
for highly efficient, low-cost large-scale racemate separations (> 100 kg) needed for
the later stages of the drug commercialization process.
The availability of a new class of efficient separations technology for chiral drugs
can have an impact on other business issues now at the forefront of the pharmaceu-
tical industry. For example, the strategy of better drug life cycle management can be