1. Gamlen Tablet Press GTP1 World’s First Bench Top Tablet Press
Unique dual mode- used as both as a tablet press and tablet hardness tester.
Portable and lightweight (20kg)
Welcome to the GTP1 -the world’s first bench top computer controlled tablet press.
This unique instrument developed for pharmaceutical use acts both as a tablet press and also tablet hardness tester.
It is both portable and lightweight making the instrument ideal for many applications in tablet research development and manufacturing. It is very easy to use.

2. Can be linked to any laptop or PC. Real time data recording.
Computer control
Can be linked to any laptop or PC.
Real time data recording.
Force displacement curves.
Ejection force.
Fracture load of compact.
The instrument is fully computer controlled and can be linked to any computer running Microsoft Windows. It provides real time data recording of Force and punch displacement during material compaction. It also measures and records tablet ejection force. When used in tablet testing mode it records load and displacement during the fracture of the tablet or compact.

3. Force Displacement profile

4. Ejection force profile

5. Fracture profile

6. 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.
The press is extremely easy to use
Simply weigh out powder directly into the die- in this example a powder pipette is used for accurate dispensing
Insert die into the press
Start compression cycle
The instrument will display the F-D data in real time including max load and subsequent ejection force readings.
4. Eject the tablet once formed
The simple features of the press will allow quick changeover of punch sizes and also mode change from tablet press to hardness tester.
No special training is required for set up and operation making it suitable for use by all levels of staff.

7. 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.
The Gamlen Tablet Press provides extremely accurate control of tablet quality.
It will control either compression force applied or resulting tablet/ compact thickness
It can control compression force in the range of 10N-5kN with force reproducibility of 1% or better.
The punch speed is controlled between 0.1mm/s– 1mm/second. This is the same speed as a single punch tablet press. Compressing a tablet takes around 40 seconds.
The final tablet/ compact thickness is controlled to 3 micrometers or better.

8. 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.
The Gamlen Tablet Press uses a V shape compression profile that has been shown to be the best way to generate comparative data on different materials. This test provides data which are easy to understand because the profile is fully reproducible and the strain rate is constant.

9. Ideal R&D, Clinical Trial and QC instrument
Test product batches.
Pre-formulation samples.
Formulation comparison.
Preclinical materials and Phase 1 CTM.
Tablets 2-13mm diameter.
Micro and multilayer tablets.
Compress 2-400mg material.
100% yield.
The advanced features of the GTP make it an ideal R&D, clinical trial and QC instrument.
Its capable of making tablets between 1 and 13mm in diameter. It will compress a minimum of 2 and maximum of 400mg material with practically 100% yield saving valuable materials.
Different shapes and sizes can also be accommodated including micro tablets. The photo shows an example of a microtablet made by the GTP.
It can also be used to make multilayer tablets. This approach is used to keep materials separate in the tablets, and for developing extended release products.

10. The force needed to make the tablet.
The GTP is a unique instrument able to measure material compressibility
Material 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.
The important aspect of the GTP is its capability to measure the compressibility of pharmaceutical materials. Why is this important ? Material Compressibility is a Critical Quality Attribute which determines the force needed to make a tablet from any particular material. It controls all tablet properties- hardness, dissolution profile, friability.

11. Risk reduction in tableting using compressibility measurements
Drug substance
Excipients
Blending
Granulation
Lubricant blending
Tableting
As such the GTP is ideal for reducing risk in the tablet development and manufacturing process by using compressibility to measure;
RM and DS quality control
Post blend material quality
Post granulation material quality
Final blend quality prior to tableting
This is because measurements taken on compacts are directly relevant to the final product and will anticipate risk of batch failure, waste of materials and expensive disposal costs.

12. 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 mg 6mm flat round tablets
Fette mg oval shaped tablets
Comparable results for tensile strength from both machines

13. Comparison for a DC product

14. DC product –solid fraction

15. WG product

16. 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 scale
Use 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

17. Tablet design and process optimisation examples
Drug substance studies
Formulation studies
Drug salt selection for compressibility.
Drug morphic form changes on compaction.
Drug supplier compressibility assessments.
Preparation of compacts for intrinsic dissolution testing.
Formulation comparison on the milligram scale (Ranking)
Multilayer tablet
Dissolution studies
Capping
Lubricant level optimisation -ejection force and compressibility
Stability studies
There are various examples where the GTP has already been used in tablet dosage form design and process optimisation. These include;
Drug salt selection for compressibility.
Drug morphic form changes on compaction.
Drug supplier compressibility assessments.
Formulation comparison on the milligram scale.
Preparation of compacts for intrinsic dissolution testing.
Lubricant level optimisation -ejection force and compressibility.

18. Heckel/ Kawakita Plots
Accurate measurement of punch displacement now enables assessment of material compressibility
GTL can help in generation of this data for your materials

19. Replacement of wet granulation with direct compression
Example Applications
Replacement of wet granulation with direct compression
Capping prediction
API supplier evaluation
Sodium bicarbonate tablet formulation
Intrinsic dissolution testing
Formulation Development
The following are examples where the Gamlen Tablet Press has been used to troubleshoot, or optimise various tableting issues.

20. Replacement of wet granulation with direct compression
Example application 1
A manufacturer of a blood pressure medicine requested that we assist in replacing the wet granulation stage with direct compression formulations. This would have considerable impact on improving the overall efficiency of the manufacturing process by saving time material costs and labour.

21. Example application- replacing wet granulation with direct compression
This is an example of the Gamlen Tablet Press in action. In this study we measured the tensile strength of tablets containing an API for blood pressure control prepared at different compaction pressures using a granule made by wet granulation and blends of the same powders but prepared for direct compression.
From the graph you can see that the direct compression formulations were more compressible than the wet granulated formulations, showing that the development of a direct compression tablet may be possible. This work was done on only about 10 grams of material.

22. Dissolution results comparing the formulations
Two direct compression formulations gave similar dissolution profiles compared to the wet granulation product.
Simple regulatory change as the excipient is not changed.
Data gathered in days with milligram quantities of material saving time cost and material.
Promising technique to improve productivity of tablet manufacturing.
Manufacturer is now considering replacing the wet granulation stage based on this data.

23. Capping prediction
Example application 2

24. 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

25. Tensile strength/compaction pressure profile – batch 1

26. Tensile strength/compaction pressure profile – batches 1 and 2

27. Tensile strength/compaction pressure profile – batches 1, 2, 3 and 4

28. 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

29. Supplier evaluation
Example application 3

30. There are 2 suppliers for the API amoxycillin.
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?

31. Comparison of Supplier 1 batches to 400MPa
Client A asked us to evaluate two raw material suppliers in respect of compressibility and batch to batch variability. Samples of two batches of Supplier 1 material were compressed (without any processing or the addition of lubricant). Compressibility of the two batches was very similar in the pressure range up to 500MPa which is the normal maximum used during tableting.

32. Comparison of supplier 1 batches full profile
To assess the capping tendency of the different sources of material, the compaction pressure range was extended to up to 700MPa. This was possible because we were using a special 3mm punch and die set which can withstand very high pressures. The strength of the tablets made from Supplier 1 material decreased rapidly at compaction pressures above the normal range.

33. Batch comparison – Supplier 2
Two batches of Supplier 2 material were compressed. Their compressibility was substantially different.
When Supplier 2 material was compressed above the normal range, the capping profile observed was different for the two batches.

34. Compressibility comparison
Supplier 1 v Supplier 2

35. 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

36. Sodium bicarbonate tablet formulation
Example application 4

37. 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

38. Effect of compaction pressure on sodium bicarbonate tablet strength

39. Effect of lubricant on the strength of sodium bicarbonate tablets

40. Effect of compaction pressure on tensile strength of formulated sodium bicarbonate tablets

41. Effect of lubricant on the strength of lubricated sodium bicarbonate tablets

42. Effect of lubrication on ejection force of formulated sodium bicarbonate tablets

43. 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

44. Intrinsic dissolution testing using the Microtest Dissolution apparatus
Example application 5

45. 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

46. Prepare small “blind” dies 3mm diameter in aluminium
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

47. MicroDiss apparatus
Dissolution vessel

48. Online UV scanning at rapid rate
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

49. Dissolution results 64
117
376
191

50. 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

51. Formulation development
Example application 6

52. 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

53. How to select the best tablet formulation?
Some desirable tablet properties go together:
Better hardness=better friability=better film coating ability
Others compete with one another:
Better (increased) hardness = worse (slower) dissolution
The 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.

54. Typical compaction force/tensile strength profile

55. All compaction force/tensile strength profiles

56. All compaction force/tensile strength profiles

57. 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

58. World’s first portable bench top tablet press/ material tester.
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.
In summary the Gamlen Tablet Press provides a unique capability in pharmaceutical material compressibility assessment and small scale tablet production.
It features advanced data capture capability together with a unique measure of material compressibility.
Use of the Gamlen Tablet Press reduces the risk of tablet problems and ultimately speeds your drug product to market.

59. Contact Gamlen Tableting Ltd.
For further details, applications and price contact: Dr Dipankar Dey Gamlen Tableting Ltd. Biocity Nottingham Nottingham NG1 1GF UK Tel: Fax:
For further information please contact Dipankar Dey or see our website