This document discusses chiral drug technology and its importance in the pharmaceutical industry. It begins by introducing resolution methods like chromatography and kinetic resolution used to separate chiral compounds. It then discusses resolving agents and how they demonstrate stereoselectivity. Examples are given of major drug products that were originally racemates but are now only marketed as single enantiomers. Chiral drug sales have grown significantly in therapeutic areas like cardiovascular and cancer. The document concludes by stating that chiral technology represents a large commercial opportunity and that consideration of chirality is important in drug research and development due to regulatory guidelines.

1. Presented by
Ch.Vamsi Anil Krishna(10AB1R0026)
Adderss:
Dept of Pharmaceutical Chemistry
Vignan Pharmacy College,Vadlamudi,
Guntur, Andhra Pradesh, India.

2.  Introduction
 Resolution Methods
 Resolving agents
 Stereoselectivity of action
 Chiral drug sales
 Chiral BIOCKBUSTER DRUGS
 Conclusion

6. Chromatography
Widely used in development laboratories
Applicable to >99% of small molecules at analytical scale
Used in manufacturing scale

7. Methods for Preparing Chiral Compounds
Chromatography

8. A small scale
separation of the
chiral compounds in
labs.

9. Handling of chromatography

10. Kinetic Resolution
 Evalution of an historical process(> 100 years)
 Based upon different reaction rates of the isomers
 Theoretically 100% yield
Technology applied on limited scale to date

11. Diastereomer Crystallisation
Most widely used technique in industry
Widely used in development
Cheap additives
Only one isomer recovered per stage

12. Resolving Agents

13. Stereoselectivity of action
S
Dextro
(+)
R
Levo
(-)

15.  Out 100 drugs sold
in 1994:
 Pure enantiomer
20%
 Racemate
21%
 No chiral
33%
 Out 100 drugs sold
in 1997:
 Pure enantiomer
30%
 Racemate
9%
 No chiral
57%

16. Racemic Mixture Single-enantiomer
Amphetamine(Benzedrine) Dextroamphetamine(Dexedrine)
Bupivacaine(Marcain) Levobupivacaine (Chirocaine)
Cetirizine(Zyrtec/ Reactine) Levocetirizine(Xyzal)
Citalopram(Celexa/ Cipramil) Escitalopram(Lexapro/ Cipralex)
Methylphinidate(Ritalin) Dexmethylphenidate(Focalin)

17. Racemic Mixture Single-enantiomer
Modafinil(Provigil) Armodafinil(Nuvigil)
Ofloxacin(Floxin) Levofloxacin(Levaquin)
Omeprazole(Prilosec) Esomeprazole(Nexium)
Salbutamol(Ventolin) Levalbuterol(Xopenex)
Zopiclone(Imovane) Eszopliclone(Lunesta)

18. $ MILLIONS 1998 1999 2000
Cardio vascular $21,906 $24,805 $26,012
Antibiotics 19,756 20,907 23,265
Cancer 8,006 9,420 13,360
Central Nervous System 7,027 8,592 13,720
Antiviral 6,131 7,540 13,446
Gastrointestinal 1,718 2,998 5,355
TOTAL $6,45,44 $74,262 $95,198

19. Chiral technology is a rapidly
developing area
Chiral technology represents a huge
commercial business opportunity
that has yet to be fully realised

21. MARKET OF CHIRAL DRUGS
Single–enantiomer drug sales show a continuous growth worldwide
and many of the top selling drugs are marketed as single enantiomers
 Annual sales of chiral drugs:
$133billion(2000), $172billion(2005)

22.  It is necessary to consider the chiral nature of a com-pound in
drug Research.
 Enantiomers of all chiral bioactive molecules must be separated
and tested.
 The FDA and regulatory authorities in Europe, China, and
Japan have provided guidelines indicating that only the active
enantiomer of a chiral drug should be brought to market.

23. Chiral drug separation
Bingyun LiDonald T. Haynie Engineering and Physics, Bionano
systems Engineering Labo Biomedical ratory, Center for Applied
Physics Studies, Louisiana Tech University, Ruston, Louisiana, U.S.A
The impact of chiral technology on the pharmaceutical industry
ANDY RICHARDS & RAY McCAGUE

24. This work was supported by
A.VISWANATH M.pharm (Ph.D)
Dept of Pharamaceutical chemisrty.
My beloved PRINCIPAL
Dr.P.SRINIVASA BABU

26. Thank you