DH 29  Development of analytical methods DH 30  Analysis of EU market products

1. G&H Meeting Jan 20 - 21, 2003 Leiden, The Netherlands WP 7 Pharmaceutics (Lichtwer Pharma) • Objectives… DH 29  Development of analytical methods DH 30  Analysis of EU market products DH 33  Development of a novel tablet DH 36  Preparation of study medication DH 31,32,34,35  Publication/Patents (Dissemination)

2. G&H Meeting,Leiden 2004 • Overall analytical method for garlic

3. 1 1 Alliin 2 unknown (Allylcysteine) 3 -Glutamyl-S-allylcysteine 4 -Glutamyl-S-trans-1-propenylcysteine 5 -Glutamyl phenylalanine 0.9 3 5 4 0.7 2 0.5 Absorption (AU) 0.3 0.1 0 2 4 6 8 10 12 14 16 18 20 22 24 Retention time [min] G&H Meeting,Leiden 2004 • Garlic under enzyme inhibiting conditions

4. 0.9 1 unknown (Allylcysteine) 2 -Glutamyl-S-allylcysteine 3 -Glutamyl-S-trans-1-propenylcysteine 4 -Glutamyl phenylalanine 5 Allicin 5 0.7 2 0.5 3 4 Absorption (AU) 1 0.3 0.1 0 2 4 6 8 10 12 14 16 18 20 22 24 Retention time [min] G&H Meeting,Leiden 2004 • Garlic under aqueous conditions

5. G&H Meeting,Leiden 2004 • Quality of EU garlic products a bumpy road!

6. G&H Meeting,Leiden 2004 • Stability of EU garlic products

7. Garlic of the future! G&H Meeting,Leiden 2004 Jungle of the market

8. G&H Meeting,Leiden 2004 Details on Stability Studies now 30 - 36 months stability Organic film based • Full compliance to ICH-guidelines • Up to seven different packaging materials • Two different dosage forms Aqueous film based • Reformulation of tablet core • Formulation of coating • Establishing aqueous coating procedure now 1 - 5 months stability

9. G&H Meeting,Leiden 2004 Organic Film Tablets (100 mg)

10. G&H Meeting,Leiden 2004 Organic Film Tablets (300 mg)

11. G&H Meeting,Leiden 2004 • Conclusion Novel Tablet (Stability) • For the organic coated tablets real time stability according EU guidelines are available for 30 – 36 months (4 time improvement!) • For aqueous coated tablets real time stability according EU guidelines are available for 1 – 5 months (ongoing studies!) a story of success!

12. G&H Meeting,Leiden 2004 • Outlook Dissemination Novel Tablet (Aqueous Coating) • A EU drug application procedure will be done when 6 months of real time stability data for the 300 mg tablets are available (3rd quarter of 2004) • A 100 mg tablet will be developed within the next 6 months according to the 300 mg one

13. G&H Meeting,Leiden 2004 • Study Medication for the Human Intervention Study - Résumé… • Tabletting Minor difficulties with the flowability and compressibility of the EU garlic powder • Coating Everything went fine… • Sugar Coating Everything went fine… • Release Full compliance with specifications! • GCP Minor deviations

14. G&H Meeting,Leiden 2004 • Publication (Dissemination) • Auger J and Haffner T et al. Congress for Hyphenated Technologies in Chromatography, February 6-8 2002, Bruges, Belgium) • Keiss H-P, Dirsch V, Hartung T, Haffner T, Truemann L, Auger J, Kahane R. and Vollmar A M. J. Nutrition 133(7), 2171-5 (2003) • Arnault, I, Christidès, J P, Mandon, N, Haffner, T, Kahane, R and AugerJournal of Chromatography A, 2003 Mar 28;991(1):69-75 • Siess M-H, Haffner T et al.. J Agric Food Chem 51, 7617-23 (2003) • Le Bon A-M, Vernevaut M.-F., Vernevaut L G., Kahane R., Auger, J., Haffner T., Siess, M.-H.. SSubmitted for publication

15. G&H Meeting,Leiden 2004 Many thanks to Marie-Hélène, Verena, Angelika, Ingrid, Anne-Marie, Jacques, and Hans-Peter… …for covering my Achilles heel – the publication work!

16. G&H Meeting,Leiden 2004 Who is a Cesar without his… A Nobody ! Silvia Striegl Wolfgang Lüdeke José Galan-Sousa Anke Wermann & Anja Müller

17. Bianca Beutke Stability Coordination G&H Meeting,Leiden 2004 Cleopatra?!

18. G&H Meeting,Leiden 2004 Thank you very much! I will miss you!