Physics of tablet compression

This presentation is about the force distribution in tablet compression, energy involved in compression,compression mechanism and evaluation of the tablet formulations.

1. PHYSICS OF TABLET COMPRESSION Mr. Sagar N Firke Dept of Pharmaceutics Nanded Pharmacy College Nanded

2. Basic terminologies before proceeding…….. Compression : Is a reduction in bulk volume as a result of applied load. Consolidation: is a phenomenon of increase in mechanical strength of the consolidated mass. Deformation: Change in a geometry due to applied forces, Strain: The relative amount of deformation produced by force called as strain. Stress: The ratio of force(F) to cause this strain at area (A) called stress.

3. COMPRESSION When external forces are applied to a powder mass, there is a reduction in its bulk volume because of following reasons. Closure repacking of the particles & Particle deformation at there point of contact. Deformation may be plastic(irreversible) or elastic (spontaneously reversible)

4. Schematic illustration of particle deformation, elastic and plastic, during compression. Fig: Particle Deformation

5. CONSOLIDATION It is defined as increase in mechanical strength of the consolidated mass. When two particles approach each other closely enough (e.g, at separation less than 50 nm) their surface free energies result in strong attractive force, a process known as Cold Welding.

6. When applied load is transmitted through the particle contacts; results in generation of considerable frictional heat. If this heat is not dissipated, it causes local rise in temperature which is sufficient to cause melting of low melting point substances.

7. FORCE DISTRIBUTION Effects of friction 1. Interparticulate Friction 2. Die wall Friction Interparticulate Friction: This arises at the particle/particle contacts & expressed as coefficient of Interparticulate friction. Expressed as µ i . Die Wall Friction: This is due to material being pressed against the die wall & moved down it. Expressed as µw.

8. FORCE DISTRIBUTION F A = F L + F D Where, F A = Is the force applied to the upper punch. F L = Proportion of applied force transmitted to lower punch. F D = Is the reaction at the die wall. F R = Radial force. FA + FL FM = ----------- 2 FM= Mean compaction force Fig:02 Force distribution

9. Development of Radial Force When the compressive stress is applied in one direction results in a decrease ( Δ H) in the height. In the case of unconfined solid body would be accompanied by expansion in the horizontal direction ( Δ D) The ratio of two dimensional changes is known as Poisson ratio λ λ = Δ D/ Δ H Consequently radial die wall force (F R ) perpendicular to the die wall surface.

10. According to classic friction theory axial frictional force F D is related to F R by the expression. FD = µw x F R Where, µw is coefficient of die wall friction Degree of lubrication can be compare by the ratio of F L to F A i.e., Coefficient of lubricant efficiency. Expressed as R value. R = F L / F A The ratio near to unity indicate perfect lubrication (0.98) & value less than 0.8 indicate poorly lubrication.

11. Ejection FORCES Radial die wall forces & die-wall friction affects the ease of tablet ejection from the die. Ejection forces follows three stages. Stage1- Peak force required to initiate ejection by breaking tablet/die-wall adhesion. Stage-02- Smaller force is required to push the tablet up the die. Stage03- Final stage is marked by declining force of ejection as tablet emerges from the die.

12. ENERGY INVOLVED IN COMPACTION Work is required , To overcome particulate friction. To Overcome friction between particle & machine . To induce elastic or plastic deformation. To operate various machine parts. Compression Process Energy Expended (Joules) Un-lubricated Lubricated Compression 6.28 6.28 Overcome die wall friction 3.35 Negligible Upper Punch withdrawal 5.02 Negligible Tablet Ejection 21.35 2.09 Total Energy 36.00 8.37

13. TABLET COMPRESSION MACHINE Tablets are made by compressing a formulation containing a drug with excipients on stamping machine called as ‘presses’ The components of tablet machine are: Fig: Hopper Fig: Set of Die & Punch Fig: Feed Frame

14. Hopper: For holding of the granules Dies: Define the size and shape of the tablet Punches: For the compressing the granules within the dies Cam tracks for guiding the movement of the punches. Feeding mechanism: distribution of granules from the hopper into the dies. Fig: Cam-Tracks

15. SINGLE PUNCH TABLET PUNCHING MACHINE Die Filling: Accomplished by gravitational flow. Tablet Formation: Upper punch enters the die & powder is compressed. Tablet Ejection: Lower punch rises until its tip reaches the level of top of the die. Fig: Sequence of tablet compression events

16. COMPRESSION CYLCLE OF ROTARY TABLET PRESS

17. COMPRESSION CYCLE Granules stored in hopper empties into feed frame (A). Pull down cam (C) guides the lower punch to the bottom & dies are allowed to overfill. Punches then pass over the weight adjustment cam(E). Wipe-off blade (D) at the end of feed frame removes the excess granules. Lower punch travel over the lower compression roll (F). Upper punch rides below the upper compression roll(G). During decompression upper punch follows raising cam(H). The lower punch ride up the cam (I).

18. EVALUATION OF TABLETS GENERAL APPEARANCE Tablet Size: Can be determine by Calliper Shape: Defined by the die shape Color : Micro reflectance Photometer Presence or absence of odour : Manual Taste: Taste Panels

19. HARDNESS “ Hardness of tablet has been defined as the force required to break a tablet in a diametric compression test” Monsanto Hardness Tester 1. It consist of barrel containing a compressible spring held between two plungers. 2 . The lower Plunger placed in a contact with tablet and zero reading is taken. 3. The upper plunger is then forced against the spring by turning threaded bolt until the tablet fractures.

20. PFIZERTESTER 1. It Consist of pairs of Pliers , as the pliers handles are squeezed, the tablet is compressed between a holding anvil and piston connected to pressure gauge. 2. The dial indicator remains at the at the reading where the tablet breaks and it can be returned to zero pressing reset button. Fig: Monsanto Hardness Tester Fig: Pfizer Tester

21. FRIABILITYTEST 1 . Tablets are subjected to combined effect of abrasion and shock 2. Apparatus consist of plastic chamber that revolves at 25 RPM dropping the tablets from the distance of 6 inches with each revolution. 3. Pre-weighed sample is placed in a friabilator which is then operated for 100 revolutions.

22. 4. Tablets are then dusted and reweighed. 5 . Material loss less than 0.5 to 1 % is acceptable. Fig: Roche Friabilator

23. WEIGHT VARIATION USP tablet weight variation test is run by weighing 20 tablets individually Calculate the average weight Compare the individual weight with average weight. The tablets meet the USP test if no more than two tablets are outside the given % limit & no tablet differs by more than two times the given % limit. Average Weight (mg) Max % difference allowed 130 mg or less 10 130-324 mg 7.5 More than324 mg 5 Table: Weight variation tolerance for uncoated tablets

24. CONTENT UNIFORMITY In this test 30 tablets are randomly selected. At least 10 of them are individually assayed. Nine of the 10 tablets must contain not less than 85 % or more than 115 % of the labled drug content. The 10 th tablet may contain less than 75 % or more than 125 % of the labeled content. If these requirements are not met, the tablets remaining from 30 must be assayed & none may fall outside the given percentage limit.

25. DISINTEGRATION TEST: Def: Disintegration It is a process in which tablet is breakdown into smaller particles known as disintegration. Instrument: The USP device consist of a basket having 6 glass tubes. Tubes are open at the top and held against 10 mesh screen at bottom. Each tablet is placed in the tube and basket rack is positioned in 1 L beaker of water, simulated gastric fluid at 37± 2 O C. A basket assembly moves up and down 5 to 6 cm at a frequency of 28 to 32 cycles/min.

26. Perforated plastic discs may be placed on top of the tablets, there are useful in low density tablets. To be compliance with the USP standards, the tablet must pass through the 10 mesh screen in the specified time. Fig: USP Disintegration test apparatus

27. DISSOLUTION STUDY Testing & interpretation can be continued through three stages if necessary. Six tablets are tested & are acceptable if all of the tablets are not less than the monograph tolerance limit(Q) + 5%. If tablet fails S1, an additional six tablets are tested(S2). The tablets are acceptable if the average of 12 tablets is greater than or equal to Q & no unit is less than Q-15%. If the tablet still fails , an additional 12 tablets are tested. Tablets are acceptable if the average of all 24 tablets is greater than or equal to Q& if not more than 2 tablets are less than Q-15.

28. THANK YOU!