Gamlen Tablet Press GTP1 World’s First Bench Top Tablet Press Unique dual mode- used as both as a...

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.

Force Displacement profile

Ejection force profile

Fracture profile

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

Comparison for a DC product

DC product –solid fraction

WG product

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

Replacement of wet granulation with direct compression

Example application 1

Example application- replacing wet granulation with direct

compression

Dissolution results comparing the formulations

Capping prediction


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


pressure profile – batches 1 and 2

0

1

2

3

4

5

6

7

8

0 100 200 300 400 500 600 700


Ten

sile

str

eng

th (

MP

a)

J20J19


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


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

Compressibility comparison Supplier 1 v Supplier 2

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


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


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


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


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


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

Intrinsic dissolution testing using the Microtest Dissolution apparatus


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 apparatus

Dissolution vessel

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

Dissolution results

64117

191

376

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

Formulation development


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


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


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

http://www.compressibility.com/

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