1. 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) G&H Meeting Jan 20 - 21, 2003 Leiden, The Netherlands WP 7 Pharmaceutics (Lichtwer Pharma)  Objectives…

2.  Overall analytical method for garlic

3.  Garlic under enzyme inhibiting conditions 0.1 0.3 0.5 0.7 0.9 024681012141618202224 Retention time [min] Absorption (AU) 1 Alliin 2 unknown (Allylcysteine) 3  -Glutamyl-S-allylcysteine 4  -Glutamyl-S-trans-1-propenylcysteine 5  -Glutamyl phenylalanine 1 2 3 4 5

4.  Garlic under aqueous conditions

5.  Quality of EU garlic products

6.  Stability of EU garlic products

7. Garlic of the future! Jungle of the market

8. Details on Stability Studies 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

9. Organic Film Tablets (100 mg)

10. Organic Film Tablets (300 mg)

11.  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!)  Conclusion Novel Tablet (Stability)

12.  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  Outlook Dissemination Novel Tablet (Aqueous Coating)

13.  TablettingMinor difficulties with the flowability and compressibility of the EU garlic powder  CoatingEverything went fine…  Sugar CoatingEverything went fine…  Release Full compliance with specifications!  GCP Minor deviations  Study Medication for the Human Intervention Study - Résumé …

14.  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 Auger Journal 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.. S Submitted for publication  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 Auger Journal 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.. S Submitted for publication

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

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

17. Bianca Beutke Stability Coordination Bianca Beutke Stability Coordination Cleopatra?!

18. Thank you very much! I will miss you!