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 , 2003 Leiden, The Netherlands WP 7 Pharmaceutics (Lichtwer Pharma)  Objectives…

 Overall analytical method for garlic

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

 Garlic under aqueous conditions

 Quality of EU garlic products

 Stability of EU garlic products

Garlic of the future! Jungle of the market

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

Organic Film Tablets (100 mg)

Organic Film Tablets (300 mg)

 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)

 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)

 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 …

 Publication (Dissemination)  Auger J and Haffner T et al. Congress for Hyphenated Technologies in Chromatography, February , 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), (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, (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 , 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), (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, (2003)  Le Bon A-M, Vernevaut M.-F., Vernevaut L G., Kahane R., Auger, J., Haffner T., Siess, M.-H.. S Submitted for publication

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

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

Bianca Beutke Stability Coordination Bianca Beutke Stability Coordination Cleopatra?!

Thank you very much! I will miss you!