Gamlen Tablet Press GTP1 World’s First Bench Top Tablet Press

1. 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)

2. Computer control • Can be linked to any laptop or PC. • Real time data recording. • Force displacement curves. • Ejection force. • Fracture load of 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.

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.

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.

9. 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.

10. 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.

11. Risk reduction in tableting using compressibility measurements Compressibility Compressibility Compressibility Compressibility Granulation Blending Lubricant blending Drug substance Excipients Tableting

12. GTP-1 scale –up to production press

13. Comparison for a DC product

14. DC product –solid fraction

15. WG product

16. Using the GTP-1 to scale up

17. Tablet design and process optimisation examples Drug substance studies Formulation studies

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. Example Applications • Replacement of wet granulation with direct compression • Capping prediction • API supplier evaluation • Sodium bicarbonate tablet formulation • Intrinsic dissolution testing • Formulation Development

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

21. Example application- replacing wet granulation with direct compression

22. Dissolution results comparing the formulations

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. 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? Supplier evaluation

31. Comparison of Supplier 1 batches to 400MPa

32. Comparison of supplier 1 batches full profile

33. Batch comparison – Supplier 2

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. 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. 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