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Gamlen Tablet Press GTP1World’s First Bench Top Tablet
Press Unique dual mode-
used as both as a tablet press and tablet hardness tester.
Portable and lightweight (20kg)
Computer control
Can be linked to any laptop or PC.
Real time data recording.
Force displacement curves.
Ejection force. Fracture load of
compact.
Simple Features and Operation
Weigh powder into die.
Insert die in press. Start compression
cycle. Eject tablet. Quick changeover
of punch sizes and mode.
No special training required for set-up and operation.
Accurate control of tablet quality
Control compression force OR tablet thickness.
Compression force control :10N-5kN/ ±1%.
Displacement Control: 0.1-1mm/s.
Thickness±3µm.
V Shape Compression Profile
Completely reproducible.
Provides detailed and accurate information as strain applied at a constant rate.
Established as the most sensitive way of comparing materials.
Ideal R&D, Clinical Trial and QC instrument
Tablets 2-13mm diameter.
Micro and multilayer tablets.
Compress 2-400mg material.
100% yield.
Test product batches.
Pre-formulation samples.
Formulation comparison.
Preclinical materials and Phase 1 CTM.
The GTP is a unique instrument
able to measure material compressibilityMaterial
Compressibility is a Critical Quality Attribute which determines The force needed to
make the tablet. All tablet properties-
hardness, dissolution profile, friability.
Currently no measure of compressibility is taken before tablet operations.
Risk reduction in tableting using compressibility measurements
Com
pre
ssib
ili
ty
Drug substanceExcipients
Blending Granulatio
nLubricant blending Tableting
Com
pre
ssib
ili
ty
Com
pre
ssib
ili
ty
Com
pre
ssib
ilit
y
GTP-1 scale –up to production press
Major pharma compared results on a formulation with the GTP-1 and the Fette 2090 rotary press.
GTP-1 -100mg 6mm flat round tablets
Fette 2090- 800mg oval shaped tablets
Comparable results for tensile strength from both machines
Using the GTP-1 to scale up
Performing small scale compactions on the GTP-1 have been shown to yield comparable results at the production scaleUse GTP-1 to optimise tensile strength and use same compaction pressure and/ or solid fraction on scale up
Considerable saving of time, materials and money using such an approach
Increase speed of drug to market
Tablet design and process optimisation examplesDrug substance
studies
Drug salt selection for compressibility.
Drug morphic form changes on compaction.
Drug supplier compressibility assessments.
Preparation of compacts for intrinsic dissolution testing.
Formulation studiesFormulation comparison on the milligram scale (Ranking)
Multilayer tablet
Dissolution studies
Capping
Lubricant level optimisation -ejection force and compressibility
Stability studies
Heckel/ Kawakita Plots
Accurate measurement of punch displacement now enables assessment of material compressibilityGTL can help in generation of this data for your materials
Example Applications
1. Replacement of wet granulation with direct compression
2. Capping prediction3. API supplier evaluation4. Sodium bicarbonate tablet
formulation5. Intrinsic dissolution testing6. Formulation Development
Capping prediction
Capping is a serious production problem, and one of the hardest to solve.
Client problem – some batches of tablets cap, but you can only tell which ones by setting up a Production tablet machine
Evaluated 4 batches on PCT (more to follow) 2 batches which cap 2 batches do not cap
Tensile strength/compaction
pressure profile – batch 1J19
0
1
2
3
4
5
6
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Te
ns
ile s
tren
gth
(M
Pa
) J19
Tensile strength/compaction
pressure profile – batches 1 and 2
0
1
2
3
4
5
6
7
8
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
J20J19
Tensile strength/compaction
pressure profile – batches 1, 2, 3 and 4
0
1
2
3
4
5
6
7
8
0 100 200 300 400 500 600 700Compaction pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
G02J20J19g04
Capping problem - conclusions
Differences observed in compressibility between good and bad batches Capping batches have lower peak
hardness and flatter compression profiles Need larger data set to confirm
significance of results Data being generated
Supplier evaluation
There are 2 suppliers for the API amoxycillin.
Material from one supplier seems to be less compressible than the other
Material from the more compressible supplier seems more variable Can we develop a test to distinguish
between the suppliers, and see differences in compressibility?
Comparison of Supplier 1 batches
to 400MPa
0
0.5
1
1.5
2
2.5
3
0 100 200 300 400 500
Compaction Pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
8601451
Comparison of supplier 1 batches
full profile
0
0.5
1
1.5
2
2.5
3
0 100 200 300 400 500 600 700
Compaction Pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
8601451
Batch comparison – Supplier 2
0
1
2
3
4
5
6
7
0 100 200 300 400 500 600 700Compaction Pressure (MPa)
Te
ns
ile
str
en
gth
(M
Pa
) 3004 E4206
Conclusions – supplier evaluation
Supplier 1 – batches consistent Supplier 2 – substantial differences in
compressibility Supplier 2 batches were more
compressible than supplier 1 Further data needed to support
definitive conclusions
Sodium bicarbonate tablet formulation
My client required a sodium bicarbonate tablet formulation with a water soluble lubricant Hard to compress, hard to lubricate
Preliminary evaluation of a proprietary compression mixture was performed
3% PEG was not found to give adequate lubrication
Each strength profile used less than 500mg of material
Effect of compaction pressure on
sodium bicarbonate tablet strength
0
0.5
1
1.5
2
2.5
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Te
ns
ile s
tren
gth
(M
Pa
)
Sodium Bicarbonate
Effect of lubricant on the strength of
sodium bicarbonate tablets
0
0.5
1
1.5
2
2.5
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Te
ns
ile s
tre
ng
th (
MP
a)
Sodi Bic
Sodi Bic + 3% macrogol 4000
Effect of compaction pressure on tensile strength of formulated
sodium bicarbonate tablets
0
1
2
3
4
5
6
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Te
ns
ile s
tre
ng
th (
MP
a)
BP
Effect of lubricant on the strength of
lubricated sodium bicarbonate tablets
0
1
2
3
4
5
6
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Te
ns
ile s
tre
ng
th (
MP
a) BP BP + 3% macrogol 4000
Effect of lubrication on ejection force of
formulated sodium bicarbonate tablets
0
100
200
300
400
500
600
700
800
0 100 200 300 400 500 600 700Compaction Pressure (MPa)
Eje
ctio
n F
orc
e (N
)
Sodium Bicarbonate
Sodium Bicarbonate + 3% PEG
Sodium bicarbonate tablet formulation conclusion
Compressibility of test formulation good No adverse effect of lubricant on hardness
profile But lubrication still inadequate – ejection forces
excessive Conclusion
Evaluate higher levels of lubricant Evaluate alternative lubricants
Measurement of intrinsic dissolution rate using small
amounts of material
Intrinsic dissolution rates are an important material property used in salt selection
However methods for measurement on small scale are not currently available
We are developing a test which will make this possible
Tablet manufacture
Prepare small “blind” dies 3mm diameter in aluminium
Compress powder samples in the dies to fixed location Powder surface
just below the die surface
Microdiss test system
Online UV scanning at rapid rate Up to 1 scan per second (? To be
confirmed) Small volumes Can look at multiple materials No need for specific analytical method
Intrinsic dissolution rate conclusion
Dissolution rate is affected by compression force
Higher compression force=lower dissolution rate
Some work needs to be done on reproducibility
Promising technique
Case study– tablet formulation
Client was preparing wet granulated from a wide range of formulation types Lactose Mannitol Avicel Range of binders
Needed to assess the most desirable formulation Evaluated 10 formulations using compaction
force/tensile strength profile
How to select the best tablet formulation?
Some desirable tablet properties go together: Better hardness=better friability=better film coating
abilityOthers compete with one another: Better (increased) hardness = worse (slower)
dissolutionThe competition between tablet hardness and
dissolution properties is often a problem.
Better compressibility is always desirable Better compressibility=lower compaction force for a
given property (hardness/dissolution/friability) so the most compressible formulation normally the best
The only exception to this would be if the process used to make it was itself undesirable.
Typical compaction force/tensile strength
profileFormulation no 13
0
1
2
3
4
5
6
7
8
9
0 100 200 300 400 500 600 700
Compaction Force (MPa)
Te
nsi
le S
tre
ng
th (
MP
a)
Mean
All compaction force/tensile strength
profilesMeans - all formulations
0
1
2
3
4
5
6
7
8
9
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
13151617181920A20
All compaction force/tensile strength
profilesMeans - all formulations and DS
0
1
2
3
4
5
6
7
8
9
0 100 200 300 400 500 600 700
Compaction pressure (MPa)
Ten
sile
str
eng
th (
MP
a)
13
1516
1718
1920A
20DS
Formulation development - conclusion
Formulation improves compressibility in all cases
Some formulations/processes substantially better than others
Picked 2 of the best formulations for further evaluation Preferred formulation was wet granulation with
no external ingredients Less preferred – significant amount of external
Avicel PH102
Gamlen Tablet Press
World’s first portable bench top tablet press/ material tester.
Advanced data capture capability.
Unique measurement of material compressibility.
Scaleable data to rotary press
Reduces risk of failure in tablet design, development and manufacture.
Contact Gamlen Tableting Ltd.
For further details, applications and price contact:Dr Dipankar DeyGamlen Tableting Ltd.Biocity Nottingham Nottingham NG1 1GFUKTel: +44 7712 632735Fax: +44 115 912 4278Email: [email protected] http://www.gamlen.co.uk