This Presentation include tablet formulation methods & instruments

1. TABLET
S. B. Thoke
[M. pharm]

2. WHAT IS TABLET …..?

3. DEFINITION
 Tablets are solid preparations
 consisting of one or more active ingredient
 obtained by compressing uniform volumes of particles into
. various shapes and sizes.

4. THE INGREDIENT CLASSIFICATION USED
IS:
 Fillers- Lactose, Starch, Dextrose, Mannitol, Sorbitol, Maltodextrin,
Sucrose, Cellulose etc.
 Binders- acacia, gelatin, liquid glucose, sucrose syrup, starch paste,
methyl cellulose, CMC, PVP, EC, HPMC etc.
 Disintegrates
 Lubricants, Glidants, Anti-adherents
 Wetting agents
 Colors and flavors
 Preservatives

5. LIST OF DISINTEGRANTS
DISINTEGRANTS
CONC. IN
SPECIAL COMMENTS
GRANULES(%)
Starch USP
5-20
Higher amount is required,
poorly compressible
Starch 1500
5-15
Avicel®(PH 101, PH
102)
10-20
Lubricant properties and
directly compressible
Cross-linked starch
Explotab®
2-8
Sodium starch glycolate,
superdisintegrant.
Crosscarmellose sodium
AC-Di-Sol®
1-3
Direct compression

6. LUBRICANTS
In tablet manufacturing one faces the problem of flow of granules from the
hopper into the die cavity, sticking of material to the punches and die walls
and release free movement of the compressed tablets from the die cavity.
To overcome these difficulties
Lubricants- prevent adhesion of the tablet material to the surface of the
dies and punches, reduce interparticle friction, facilitate an easy ejection of
tablets from the die cavity and improves rate of flow of tablet granulation.
Eg. Talc, magnesium stearate, calcium stearate, stearic acid, hydrogenated
vegetable oil and PEG.
The quantity of lubricant significantly varies from 0.1 to 5%.

7. LIST OF LUBRICANTS
Lubricants
Conc.
Comments
Stearates(Magnesium Stearate,
0.25 -1
Calcium Stearate, Sodium stearate)
Reduce tablet strength; prolong
disintegration; widely used.
Talc
1 -2
Insoluble but not hydrophobic;
moderately effective.
Glyceryl behapate
(Compritol®888)
1-5
Both lubricant and binder;

8. GLIDANTS
Glidant Improves the flow characteristics of a powder mixture.
 Always added in the dry state just prior to compression.
Eg. colloidal silicon dioxide (Cabosil®, Cabot®) and asbestos free talc etc.
 They are used in concentration less than 1%.
 Talc is also used and may serve the dual purpose of lubricant/glidant.
Glidants
Range
Colloidal silica i.e. syloid, pyrogenic silica
0.25%
Hydrated sodium silioaluminate
0.75%

9. ANTIADHERENTS
 Some material have strong adhesive properties towards the metal of
punches and dies or the tablet formulation containing excessive moisture
which has tendency to result in picking and sticking problem.
 Antiadherent prevent sticking to punches and die walls.
Eg. Talc, magnesium stearate and corn starch etc.
Antiadherants
Range
Comments
Talc
1–5
Lubricant with excellent antiadherents properties
Cornstarch
3 –10
Lubricant with excellent antiadherents properties
Sodium lauryl sulfate
<1
Antiadherents with water soluble lubricant
Colloidal silica
0.1 – 0.5
Does not give satisfactory results due to small
surface area. Cab-O-Sil® and Syloid®
Stearates
<1
Antiadherents with water insoluble lubricant

10. COLORS
 Natural vegetable colors – limited availability & unstable
 FD&C and D&C approved dyes are used.
 Either added in dry granulation mix or in vehicle used for wet
granulation.
 Lake dyes ( dyes absorbed on alumina or aluminium hydroxide) are used
in dry granulation.
 Dyes tend to fade on standing and exposure to light leads to mottling.
 Eg. FD&C approved lakes and dyes – lake sunset yellow, brilliant blue,
ferric oxide.

11. FLAVORS
 Flavor's are usually limited to tablets intended to dissolve in the mouth.
 In generally water soluble
 Little acceptance in manufacturing due to poor stability.
 Do not affect any physical characteristics of the tablet granulation.
 Incorporated by spraying them on to the granules in the form of solutions
in some volatile organic solvent.
 Also can be incorporated with lubricants
 Proportion limited to 0.5 %
 Excess quantity will interfere with free flow of granules
e.g. Raspberry, Pineapple, Peppermint, Blackcurrant, Orange, Mango,
Strawberry etc.

12. SWEETENERS
 Use is primarily limited to tablets meant to dissolve in oral cavity
 Mannitol – 72% as sweet as sucrose
 Earlier saccharin was the only artificial sweetener used. It is 500 times
sweeter than sucrose but has a bitter aftertaste and also carcinogenic
properties.
 Aspartame is the new sweetener- disadvantage is its instability in the
presence of moisture.

13. Content uniformity

Uniform chemical composition.

Good mixing is essential, and segregation during the process
should be prevented.
Three main manufacturing methods are used to prepare the running
powder:
1. Wet granulation
2. Direct compression
3. Dry granulation or slugging

14. WET GRANULATION
Wet granulation is a process of dry mixing, wet mixing, and particle
size enlargement, and is a process of particle attachment
(agglomeration).
It consists of six steps:
1. Dry mixing
2. Wet mixing
3. Milling of the wetted mass
4. Drying
5. Milling of the dried mass
6. Final blending

15. Wet Granulation
Mix powders
Mill coarsely
Add binder
Dry
Compress or
fill into capsules
Mill
Blend & lubricate

16. ADVANTAGES OF WET GRANULATION
 Physical characteristics of the drug are usually not important.
 The coalescing of particles locks in blend uniformity.
 A wide variety of powder materials can be processed into a uniform
mix with improved flow.
 Optimum fill density can be achieved by adjusting the process to create
the optimum final particle size distribution.
 Compressibility and consolidation are improved via the choice of the
correct binder and the moisture content of the granules.

17.  Dissolution is modified through hydrophilization to improve wetting
or, with the choice of more insoluble binders, to obtain a modified
release pattern.
 Dust and segregation tendencies are reduced.

18. DISADVANTAGES OF WET GRANULATION
 Large number of process steps; each step requires qualification,
cleaning, and cleaning validation.
 Long process time, particularly for drying.
 High labor and manufacturing costs.
 Some material loss during processing.
 Problems associated with heat and solvent sensitive drugs.
 Capital requirements for extra building space and equipment.
 Upon aging, dissolution from granules can be slowed after tableting.

19.  Assay problems may occur for low dosage drugs due to incomplete
extraction if the active ingredient is complexed by the binder, or
adsorbed onto one of the other excipients.
 Still no exact way to determine granulation endpoint (torque, power
consumption, etc.).

20. SINGLE-STEP FLUID BED WET
GRANULATOR
Fluid-bed granulator
Binder solution spray
Warm air flow

21. DIRECT COMPRESSION
 This is, a two-step process involving screening and/or milling and final
mixing.
 An effective binder is needed and should have good compression and
consolidation properties as a dry additive, even at low concentrations
(< 30%) in the formulation.
 Good adhesive properties in the dry form are a combination of a rough
and porous surface combined with a van der Waal's and/or a hydrophilic
bonding mechanism to attach the active ingredient(s) to the excipient.
This feature is needed to assure good mixing of drug and excipients and
to prevent segregation.

22. ADVANTAGES OF DIRECT COMPRESSION
 Economy in labor, time, equipment, operational energy, and space.
 Problems due to heat and moisture eliminated.
 Greater physical stability provided; hardness and porosity changes
less with time when direct compression is broadly compared to wet
granulation systems.
 Extraction of the drug from the dosage form is not inhibited during
the assay procedure (polymer binding).
 Choice of ingredients allows the formulator to improve or retard
dissolution rate.

23. DISADVANTAGES OF DIRECT
COMPRESSION
 Critical nature of the raw materials; need for greater quality control in
purchasing to assure batch uniformity.
 Difficulty obtaining dense hard tablets for high-dose drugs.
 Non-homogenous distribution of low-dose drugs due to segregation after
blending (content uniformity).
 Sensitivity of direct compression 'running' blends to over lubrication.
 Limitations in color variations.
 Need for assisted feed and precompression for some high-dose drugs.
 Need for commensurate particle size or particle size distribution between
drug and excipients.

24. DRY GRANULATION
Roller Compactor
It consists of five steps:
1. Mixing
2. Roller compaction
3. Milling
4. Screening
5. Final blending

25. Roller compactor
"Chilsonator”
Compact
Size reduction of
compacts into
granules
Powder to be
compacted

29. FINAL BLENDING
Final blending is usually done in a cone or V-type blender,
To obtain the final blend, it is necessary to consider the objectives of the
mixing steps:
1. To achieve drug content uniformity
2. To obtain uniformity of flow and bulk density
3. To effect distribution of lubricant, color, and surface active agents
4. To reduce or eliminate segregation

30. FINAL BLENDING
Compress or
fill into capsules
Mill
Blend & lubricate

31. EQUIPMENT'S USED FOR MIXING,
BLENDING AND LUBRICATION
 High share mixers
 Tumbling mixers
 Y-cone
 Rotating cube
 Double cone
 Fluidized bed
 Agitator mixers
 Ribbon blender

32. TUMBLE
BLENDERS

33. DRY MIXING EQUIPMENT'S
Sigma blade mixer
Planetary mixer

34. Littleford Lodige mixers

35. GRANULATOR MIXER
Diosna mixer
RMG

36. EQUIPMENT'S USED IN SIEVING

37. COMPRESSION
Tableting procedure
 Filling
 Compression
 Ejection
Tablet compression machines
 Hopper for holding and feeding granulation to be compressed
 Dies that define the size and shape of the tablet
 Punches for compressing the granulation within the dies
 Cam tracks for guiding the movement of the punches
 Feeding mechanisms for moving granulation from the hopper into the
dies

38. SINGLE PUNCH MACHINE
 The compression is applied by the upper punch
 Stamping press

39. Upper and
Lower Collar
Collar locker

40. Common stages occurring
during compression
 Stage 1: Top punch is
withdrawn from the die by the
upper cam. Bottom punch is
low in the die so powder falls
in through the hole and fills
the die
 Stage 2: Bottom punch moves
up to adjust the powder
weight-it raises and expels
some powder
 Stage 3: Top punch is driven
into the die by upper cam.
Bottom punch is raised by
lower cam. Both punch heads
pass between heavy rollers to
compress the powder
 Stage 4: Top punch is
withdraw by the upper cam.
Lower punch is pushed up and
expels the tablet. Tablet is
removed from the die surface
by surface plate
 Stage 5: Return to stage 1

41. MULTI-STATION ROTARY PRESSES
 The head of the tablet machine that holds the upper punches, dies
and lower punches in place rotates.
 As the head rotates, the punches are guided up and down by fixed
cam tracks, which control the sequence of filling, compression and
ejection.
 The portions of the head that hold the upper and lower punches are
called the upper and lower turrets.
 The portion holding the dies is called the die table.

42. DIES & PUNCHES
Lower punch
Upper punch
Dies

44. COMPRESSION CYCLE
 Granules from hopper empty in the feed frame (A) containing several
interconnected compartments.
 These compartments spread the granulation over a wide area to
provide time for the dies (B) to fill.
 The pull down cam (C) guides the lower punches to the bottom,
allowing the dies to overfill
 The punches then pass over a weight-control cam (E), which reduces
the fill in the dies to the desired amount

46.  A swipe off blade (D) at the end of the feed frame removes the excess
granulation and directs it around the turret and back into the front of the
feed frame
 The lower punches travel over the lower compression roll (F) while
simultaneously the upper punches ride beneath the upper compression
roll (G)
 The upper punches enter a fixed distance into the dies, while the lower
punches are raised to squeeze and compact the granulation within the
dies
 After the moment of compression, the upper punches are withdrawn as
they follow the upper punch raising cam (H)
 The lower punches ride up the cam (I) which brings the tablets flush
with or slightly above the surface of the dies

47.  The tablets strike a sweep off blade affixed to the front of the feed
frame (A) and slide down a chute into a receptacle
 At the same time, the lower punches re-enter the pull down cam (C)
and the cycle is repeated

48. HIGH SPEED ROTARY
MACHINE
MULTI ROTARY MACHINE

49. 49
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25-02-2013