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May 5, 2003
Volume 81, Number 18
CENEAR 81 18
ISSN 0009-2347
CONSTANT

Chiral separations are enduring items in the toolbox

Predictions that resolutions of racemates will fade away in favor of asymmetric syntheses may take a long time to be fulfilled, if at all. Chiral chromatography as a route to single-enantiomer drugs will stay in the chiral toolbox as long as processes and materials continue to meet the pharmaceutical industry's demands for high productivity at low cost and short development times.

"Chromatography is the fastest, most expedient method to obtain the pure enantiomers of a racemate," says Thomas B. Lewis, president and chief executive officer of Chiral Technologies, a supplier of chiral chromatographic separation products. Chiral chromatography using a simulated moving-bed system (SMB), for example, is rapidly becoming a workhorse in drug development.

Units have been installed at Bayer, Carbogen, Chiral Technologies, GlaxoSmithKline, Merck, Novartis, Novasep, Pfizer, and Pharmacia. Commercial-scale systems are operating at Aerojet, Finorga, H. Lundbeck, Honeywell, UCB Pharma, and Chiral Technologies' parent, Daicel Chemical. The largest units are processing up to 200 metric tons of material per year.

SMB takes only months to develop compared with two to five years for asymmetric methods, which in turn cost two to five times to develop compared with SMB. "We expect chiral chromatographies to evolve and grow parallel to the growth of single-enantiomer, small-molecule drugs," Lewis says. Constant improvement is key. More efficient stationary phases and better commercial-scale processes will ensure that "chromatography as a process technology is viewed on equal footing as other chiral technologies," he adds.

Integrated chiral chromatographic systems are becoming mandatory tools in chemical process R&D departments, says Jean Blehaut, CEO of NovaSep. Coupled with direct crystallization, chiral chromatography can be very powerful.

In 90% of cases, the phase diagram of a compound allows a high optical purity to be reached by simple direct crystallization of an enantiomer that has been preenriched by chromatography. "You can kill several birds with one stone," Blehaut says. "Improve throughput and ruggedness by designing the chromatography for a lower optical purity; reach the desired chemical and enantiomeric purities in one crystallization step; and if the separation occurs at the level of the active ingredient, control the polymorph through the crystallization."

SMB, which is a continuous process, also aligns with the slowly growing trend to use continuous processes in pharmaceutical manufacturing. Blehaut notes the approval by the Food & Drug Administration last August of Lexapro (escitalopram), the S-enantiomer of the antidepressant Celexa (citalopram), as the first for a single-enantiomer drug produced by SMB technology. NovaSep developed and scaled up the process to the ton scale and then engineered and commissioned complete systems at the production sites of the drugmaker, H. Lundbeck. "The approval was a big deal because it cleared some concerns regarding the "validatability" of continuous chromatographic processes," Blehaut tells C&EN. "That issue is now behind us."

Blehaut estimates that the total installed continuous-chromatography separation capacity in the pharmaceutical industry is 1,200 metric tons per year. "One does not scale up a new technology to such a level if it is not significantly cheaper than traditional technologies," he says. And given the increasing workload of R&D and engineering teams at Novasep, he adds, "I believe that the share of chromatographic processes among chiral technologies will continue to grow in the years to come."


COVER STORY
CHIRAL BUSINESS
Fine chemicals companies are jockeying for position to deliver the increasingly complicated chiral small molecules of the future

CONTEST
Vying For Chiral Hydroformylation Advantage

NICHE PLAYER
Chiral Quest Sees Advantages In Independence

STEADY SHARE
Worldwide sales of single-enantiomer pharmaceutical products approach $160 billion

BLOCKBUSTERS
Top 10 single-enantiomer products belong to billion-dollar club

CHIRALITY AT WORK
Drug developers can learn much from recent successful and failed chiral switches

REALITY CHECK
When Chemistry Bows To Economics

HARVEST
Research in Chiral Fine Chemicals Reaps Recognition

CONSTANT
Chiral separations are enduring items in the toolbox

CASE HISTORIES
History and choice shape portfolios

CALENDAR
Events Of Interest






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Chemical & Engineering News
Copyright © 2003 American Chemical Society



 
Visit SGI
COVER STORY
CHIRAL BUSINESS
Fine chemicals companies are jockeying for position to deliver the increasingly complicated chiral small molecules of the future

CONTEST
Vying For Chiral Hydroformylation Advantage

NICHE PLAYER
Chiral Quest Sees Advantages In Independence

STEADY SHARE
Worldwide sales of single-enantiomer pharmaceutical products approach $160 billion

BLOCKBUSTERS
Top 10 single-enantiomer products belong to billion-dollar club

CHIRALITY AT WORK
Drug developers can learn much from recent successful and failed chiral switches

REALITY CHECK
When Chemistry Bows To Economics

HARVEST
Research in Chiral Fine Chemicals Reaps Recognition

CONSTANT
Chiral separations are enduring items in the toolbox

CASE HISTORIES
History and choice shape portfolios

CALENDAR
Events Of Interest


Related Stories
Custom Chemicals
[C&EN, Feb. 17, 2003]

Pharma Business
[C&EN, Jan. 27, 2003]

Fine Chemicals
[C&EN, July 22, 2002]

Chiral Chemistry
[C&EN, Jun. 10, 2002]

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