dh 29 development of analytical methods dh 30 analysis of eu market products dh 33 development of...
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DH 29 DH 29 Development of analytical methods Development of analytical methods
DH 30 DH 30 Analysis of EU market products Analysis of EU market products
DH 33 DH 33 Development of a novel tablet Development of a novel tablet
DH 36 DH 36 Preparation of study medication Preparation of study medication
DH 31,32,34,35 DH 31,32,34,35 Publication/Patents (Dissemination) Publication/Patents (Dissemination)
G&H Meeting Jan 20 - 21, 2003G&H Meeting Jan 20 - 21, 2003Leiden, The NetherlandsLeiden, The Netherlands
WP 7 Pharmaceutics (Lichtwer Pharma)WP 7 Pharmaceutics (Lichtwer Pharma)
Objectives…Objectives…
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Overall analytical method for garlicOverall analytical method for garlic
0 10 20 30 40 50 60min
1 234
5
6
7
1 Alliin2 g-Glutamyl-S-allylcysteine3 g-Glutamyl-S-trans-1-propenylcysteine4 g-Glutamyl phenylalanine5 Allicin6 Dithiines7 Sulfides
Garlic under enzyme inhibiting conditionsGarlic under enzyme inhibiting conditions
0.1
0.3
0.5
0.7
0.9
0 2 4 6 8 10 12 14 16 18 20 22 24
Retention time [min]
Ab
sorp
tio
n (
AU
)
1 Alliin2 unknown (Allylcysteine)3 g-Glutamyl-S-allylcysteine4 g-Glutamyl-S-trans-1-propenylcysteine5 g-Glutamyl phenylalanine
1
2
34
5
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Garlic under aqueous conditionsGarlic under aqueous conditions
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
0.1
0.3
0.5
0.7
0.9
0 2 4 6 8 10 12 14 16 18 20 22 24
Retention time [min]
Ab
sorp
tio
n (
AU
)
1
2
3 4
51 unknown (Allylcysteine)2 g-Glutamyl-S-allylcysteine3 g-Glutamyl-S-trans-1-propenylcysteine4 g-Glutamyl phenylalanine5 Allicin
0
0,5
1
1,5
2
2,5
3
Alliin Allicin Peptides
Co
nte
nt
[%]
AUT 1
AUT 2
GER 1
ITA 1
ITA 2
NL 1
NL 2
SWE 1
SWE 2
SWE 3
UK 1
Quality of EU garlic productsQuality of EU garlic products
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Stability of EU garlic productsStability of EU garlic products
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
0
20
40
60
80
100
Re
fere
nc
e
AU
T 1
AU
T 2
GE
R 1
ITA
1
ITA
2
NL
1
NL
2
SW
E 1
SW
E 2
SW
E 3
UK
1
AlliinAllicinPeptides
% o
f s
tart
ing
va
lue
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Garlic of the future!
Jungleof the market
Details on Stability StudiesDetails on Stability Studies
Organic film basedOrganic film based Full compliance to ICH-guidelinesFull compliance to ICH-guidelines Up to seven different packaging materialsUp to seven different packaging materials Two different dosage formsTwo different dosage forms
Aqueous film basedAqueous film based Reformulation of tablet coreReformulation of tablet core Formulation of coatingFormulation of coating Establishing aqueous coating procedureEstablishing aqueous coating procedure
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Commercial Products (Dragees)100mg and 300mg
0
10
20
30
40
50
60
70
80
90
100
0 6 12 18 24 30 36Months
rel.
Act
ivit
y (%
)
100mg Tablets; Standard Polymer Blister; 25°/60%
100mg Tablets; Standard Polymer Blister; 40°/75%
300mg Tablets; Standard Polymer Blister; 25°/60%
300mg Tablets; Standard Polymer Blister; 40°/75%
Tolerance
100 mg Tablets - 25°C / 60% Long Term Condition; Climatic Zone IV
40
50
60
70
80
90
100
0 6 12 18 24 30 36Months
rel.
Act
ivit
y (%
)
PVDC 60 Polymer/Alu Blisterpure Alu/Alu Blister Alu/Alu Polymer Composite Blister PE Bottles Glass Bottles
Tolerance
OrganicOrganic Film Tablets (100 mg) Film Tablets (100 mg)
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
300 mg Tablets 25°C / 60%Long Term Condition; Climatic Zone II
30
40
50
60
70
80
90
100
110
0 6 12 18 24 30 36Months
rel.
Act
ivit
y (%
)
PVDC 60 Polymer/Alu Blisterpure Alu/Alu Blister Alu/Alu Polymer Composite Blister PE Bottles Glass Bottles
Tolerance
OrganicOrganic Film Tablets (300 mg) Film Tablets (300 mg)
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
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)Conclusion Novel Tablet (Stability)
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
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 Outlook Dissemination Novel Tablet (Aqueous Coating)(Aqueous Coating)
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
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
Study Medication for the Study Medication for the Human Intervention Study - Human Intervention Study - RésuméRésumé ……
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Publication (Dissemination)Publication (Dissemination)
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
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
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
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Many thanks toMany thanks to
Marie-Hélène, Verena, Angelika, Marie-Hélène, Verena, Angelika,
Ingrid, Anne-Marie, Jacques, and Ingrid, Anne-Marie, Jacques, and
Hans-PeterHans-Peter… …
……for covering my for covering my Achilles heelAchilles heel – –
the publication work!the publication work!
Who is a Who is a Cesar Cesar without his… without his…
A A NobodyNobody ! !
Wolfgang LüdekeWolfgang Lüdeke José Galan-SousaJosé Galan-SousaSilvia StrieglSilvia StrieglAnke Wermann
& Anja Müller
Anke Wermann &
Anja Müller
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Bianca BeutkeStability
Coordination
Bianca BeutkeStability
Coordination
Cleopatra?!
Cleopatra?!
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
Thank you Thank you very much!very much!
I will miss you!I will miss you!
G&H Meeting,G&H Meeting, Leiden 2004Leiden 2004
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