The Gamlen Tablet Press (GTP)

1. The Gamlen Tablet Press (GTP) Michael Gamlen Gamlen Tableting Ltd

2. Gamlen Tablet Press GTP1World’s First Bench Top Tablet Press • Computer control of compaction force and compaction speed • Can be used as both as a tablet press and tablet hardness tester. • Portable and lightweight (20kg) • Simple to use

3. Computer control Can be linked to any laptop or PC. The system records: • Real time compression and punch position • Force-displacement curves • Ejection force • Able to perform multiplecompactions • Easy to make layeredtablets or test precompression

4. Accurate control of tablet quality • Control compression force, maximum 5kN ±1%. • Displacement rate:0.1-1mm/s. • Can be used to control thickness±3µm. • Data capture rate 10-2000Hz

5. Operation of the press is simple and easy to learn

6. Weigh the powder into the die using a balance

7. Place the die in the press

8. Select the compression parameters • Compression parameters are set for each compaction using the computer display • Values are carried forward to the next compaction ready for editing

10. Data display area

11. Machine display

12. Data input area

13. SelectcompressionmodeCan also use Tablet Thickness or Fracture modes

14. Select compression speed1-60 mm/min

15. Select maximum compression force5-500 kg

16. Die diameter and Die HeightEnter values for the die in use. Dies available 2-10mmNormal size 5 or 6 mm

17. Number of compactions1 or more as required

18. EjectionIf selected, the machine will eject the tablet. If not selected, the die must be removed for ejectionUsed for rapid ejection.

19. Data capture rate200Hz recommended for most purposes

20. Click on the Test button and Enter a reference for the tablet • The reference will be stored and written to the Excel data capture file • The tablet will then be compressed

21. Typical compression display Force (kg) Displacement (mm)

22. Slide the die to the ejection position

23. Eject the tablet Ejection – Polyplasdone XL

24. Eject the tablet Ejection – Avicel PH102

25. Slide the die slide back and remove the tablet from the die slide

26. Applications of the Gamlen Tablet Press

27. Ideal R&D, Clinical Trial and QC instrument • Testing product batches • Manufacture samples for compatibility tesing • Comparison of Formulations • Manufacture of preclinical materials and Phase 1 CTM • Comparison of API suppliers Formulation

28. Testing product batches

29. Comparison of GTP and Production tablet press, direct compression product Tablet strength Tablet density

30. Comparison of GTP and Production tablet press, wet granulated product Tablet strength Tablet density

31. Using the GTP-1 to scale up

32. Example Applications • Replacement of wet granulation with direct compression • API supplier evaluation • Lubrication studies • Formulation Development

33. Replacement of wet granulation with direct compression Example application 1

34. Replacing wet granulation by direct compression without changing formula Compressibility Tablet strength Compaction pressure

35. Replacing wet granulation by direct compression without changing formula Pass specification % Dissolved Fail specification Time

36. Supplier evaluation Example application 2

37. Amoxycillin supplier evaluation Evaluation of 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?

38. Comparison of Supplier 1 batches to 400MPa

39. Comparison of two batches from supplier 1

40. Batch comparison – Supplier 2

41. Compressibility comparison Supplier 1 v Supplier 2

42. 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

43. Ejection studies – sodium bicarbonate tablet formulation Example application 3

44. Sodium bicarbonate tablet formulationSummary • 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

45. Effect of compaction pressure on sodium bicarbonate tablet strength

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

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

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

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

50. 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