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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.

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Presentation on theme: "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."— Presentation transcript:

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)

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 Drug substance Excipients BlendingGranulation Lubricant blending Tableting Compressibility

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-1 -100mg 6mm flat round tabletsFette 2090- 800mg 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 Drug salt selection for compressibility. Drug morphic form changes on compaction. Drug supplier compressibility assessments. Preparation of compacts for intrinsic dissolution testing. Formulation studies Formulation comparison on the milligram scale (Ranking) Multilayer tabletDissolution studiesCapping Lubricant level optimisation -ejection force and compressibility Stability 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 1.Replacement of wet granulation with direct compression 2.Capping prediction 3.API supplier evaluation 4.Sodium bicarbonate tablet formulation 5.Intrinsic dissolution testing 6.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) o 2 batches which cap o 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 o Capping batches have lower peak hardness and flatter compression profiles  Need larger data set to confirm significance of results o Data being generated

29 Supplier evaluation Example application 3

30 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

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 o 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 o But lubrication still inadequate – ejection forces excessive  Conclusion o Evaluate higher levels of lubricant o 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 o Up to 1 scan per second (? To be confirmed) o Small volumes o Can look at multiple materials o No need for specific analytical method

49 Dissolution results 64 117 191 376

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 o Lactose o Mannitol o Avicel o Range of binders  Needed to assess the most desirable formulation o 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

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 o Preferred formulation was wet granulation with no external ingredients o Less preferred – significant amount of external Avicel PH102

58 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.

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: +44 7712 632735 Fax: +44 115 912 4278 Email: dip@pharmdservices.com http://www.gamlen.co.uk http://www.gamlen.co.uk


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