3. TABLETS
Tablets are solid preparations
Consisting of one or more active ingredient
Obtained by compressing uniform volumes
of particles into various size and shape.
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4. THE ADVANTAGES OF THE TABLET
• They are unit dosage
• Greatest dose precision and the least content
variability.
• Cost is lowest of all oral dosage form.
• Lighter and compact.
• Easiest and cheapest to package.
• Easy to swallowing .
• Special release product is possible by enteric coating
or delayed release product.
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5. • odour and bitter taste can be masked by coating
technique.
• Suitable for large scale production.
• Greatest chemical ,mechanical and microbial
stability over all oral dosage form.
• Product identification is easy and cheapest.
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6. DISADVANTAGES OF TABLET
• Difficult to swallow in case of children and unconscious
patients.
• Some drugs resist compression into dense compacts.
• Drugs with poor wetting, slow dissolution properties, is
difficult to formulate.
• Bitter testing drugs, drugs with an objectionable odor or
drugs that are sensitive to oxygen may require
encapsulation or coating.
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7. DIFFERENT TYPES OF TABLETS
(A) Tablets ingested orally:
1. Compressed tablet. e.g. Paracetamol tablet
2. Multiple compressed tablet.
• layered tablet.
• Compression coated tablets.
4. Delayed release tablet. e.g. Enteric coated Bisacodyl
5. Sugar coated tablet. e.g Multivitamin tablet
6. Film coated tablet. e.g. Metronidazole tablet
7. Chewable tablet. e.g. Antacid tablet
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8. Tablets used in oral cavity
1. Buccal tablet e.g. Vitamin-c tablet
2. Sublingual tablet e.g. Vicks Menthol tablet
3. Troches or lozenges
4. Dental cone
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9. (c) Tablets administered by other route:
1. Implantation tablet
2. Vaginal tablet, e.g. Clotrimazole tablet
(D) Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet (Aspirin)
2. Dispensing tablet, e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet
4. Tablet triturates e.g. Enzyme tablet (Digiplex)
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10. TABLET GRANULATION
Granulation: The process in which the primary powders
particles are made adhere to form larger Multi particle entities
called granulation.
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11. Powders intended for compression into tablets must possess
two essential properties.
Powder fluidity or flowability
• Powder flow can be improved mechanically by the use of
vibrators, glidant.
Powder compressibility
• The property of forming a stable, intact compact mass
when pressure is applied is called powder
compressibility.
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11
12. ADVANTAGES OF GRANNULATION
• To avoid powder segregation.
• To enhance the flow of powder.
• To produce uniform mixtures.
• To produce dust free formulations.
• To eliminate poor content uniformity.
• To improve compaction characteristics
of mix.
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13. Manufacturing of granules
Dry granulation method wet granulation method
Direct compression
compression
granulation.
Wet granulation.
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16. Direct compression
Some Crystalline substances can compress directly.
Directly compressible diluent is an
Inert
Compactable
Maintain compression capacity even after adding disintegrates and
other ingredients.
Direct compression materials should posses
Good flow and compressibility
Inert
Tasteless
Reworkable
Inexpensive
Able to disintegrate.
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19. COMPRESSION GRANNULATION
Dose of a drug is too high for its compression.
Drug sensitive to heat and moisture.
Aspirin, multi vitamins.
Compaction of components of tablets by means of
tablet press or machine.
Milling and screening prior to fluid compression.
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20. Roller compactor
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On a large scale compression
granulation can also be performed on a
roller compactor.
Granulation by dry compaction can also
be achieved by passing powders between
two rollers that compact the material at
pressure of up to 10 tons per linear inch.
21. It requires drugs or excipients with cohesive properties.
Large particles must be used → (acceptable flowability and
bulk density)
If the drug powder has low compatability, it is difficult to
form into tablets.
Needs directly compressible filler that is usually expensive, e.g.
microcrystalline cellulose (Avicel), spray dried lactose.
LIMITATIONS OF DRY GRANULATION21
22. WET GRANULATION
It involves massing of a mix of dry Primary powder
particles using a Granulating fluid.
The fluid contain a solvent that must be Volatile and
non-toxic eg water, Ethanol.
The granulating solvent may contain a Binding agent
to ensure particle Adhesion after drying.
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23. 23
• End point is tested by pressing a portion of the mass in
the palm, if it crumbles (passed) under moderate
pressure then, the mixture is ready for wet screening.
24. Advantages of wet granulation
prevent segregation of the constituents of
the powder blend.
Improved cohesiveness and
compressibility.
To improve homogeneity .
Uniform distribution of contents and
colour .
The dissolution rate of hydrophobic drugs
may be improved by wet granulation
method.
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25. Limitations of wet granulation:
• Multiple separate steps are involved.
• Not suitable for heat and moisture sensitive drugs
• It is an expensive process-
• Cannot be used for moisture sensitive drugs.
• The use of soluble dyes often lead to migration of
dyes during drying stage.
Equipments
Traditionally, dry mixing in wet granulation
process has been carried out using,
Sigma blade mixer,
Heavy-duty planetary mixer.
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26. Granulation mechanism
To form grannules,bond must be formed between
powder particles
So they adhere
Bond should be strong to prevent break down.
5 bonding mechanism
Adhesion and cohesion
Interfacial forces
Mechanical interlocking
Attractive forces between soild particles
Formation of solid bridges after solvent
evaporation.
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27. Mechanism of granule formation
Divided into 3
Nucleation
Transition
Ball growth
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29. 29
Single pot granulation
The granulation is done in a normal
high shear processor and dried in same
equipment.
e.g. Single Pot Processor /
One-Pot Processor
32. High shear mixture granulation32
Dry Powder mixing (Approx 2-5 mins)
Liquid binder addition (Approx 1-2 mins)
Wet massing
Wet sieving of granules
Drying
Dry sieving of granules
33. 33
Short processing time.
Lesser amount of liquid
binders required .
Highly cohesive material
can be granulated.
Increase in
temperature may cause
chemical degradation
of thermolabile
material.
Over wetting of
granules can lead to large
size lumps formation.
ADVANTAGES DISADVANTAGES
34. Fluid bed granulator34
Fluidization is the operation by which fine
solids are transformed into a fluid like state
through contact with a gas.
Granulating and drying can be completed in one
step inside the machine.
36. Advantages
Reduces dust formation during
processing
reduces product loss.
Improves worker safety.
process suitable to:
Potent compounds
Minimizing product/operator
Exposure
Minimizing cross contamination.
Reduced process time
Reduced equipment and floor
space requirements.
DISADVANTAGES
The Fluid Bed cleaning is
labor-intensive and time
consuming.
Difficulty of assuring
reproducibility.
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38. The common
types of tablet’s
excipients are
described in the
figure.
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Diluents
Binders $
adhesives
Disintegrants
Colours,
sweeteners
$ flavors
39. Diluent or filler
Bulking agent.
Increase size of the tablet.
Suitable for handling.
Most common fillers in tablets:
1. Lactose.
2. Sugar or sugar alcohol (glucose,sucrose, sorbitol and
mannitol).
3. Cellulose and microcrystalline cellulose.
4. diCalcium phosphate dihydrate.
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40. Requirements for a good diluent
Chemically inert, biocompatible, cheap.
Non-hygroscopic.
Good biopharmaceutical properties.
water soluble or hydrophilic.
compatibility
Have an acceptable taste.
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41. Disintegrants
To ensure that the tablet, when in contact with a
liquid,
breaks up into small fragments,
which promotes rapid drug dissolution.
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42. Steps of the disintegration process
First: The liquid wets the solid
and penetrates the pores of the
tablet.
tablet breaks into smaller
fragments
(aggregates of primary
particles).
Second: The aggregates will
deaggregate into their primary
powder particles.
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43. The Method of Disintegrant Addition
Mixed with other ingredients prior to granulation &
thus incorporated within the granules
(INTRAGRANULAR ADDITION).
Mixed with the dry granules.(EXTRA GRANULAR
ADDITION).
Incorporated as both an intragranular and an extra
granular portion.
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44. Commonly Used Disintegrants
1. Starch.
2.Cellulose (e.g. sodium carboxymethyl cellulose).
Typical concentration of 1-5% by weight
3. High swelling disintegrants
(Modified Starch or Modified cellulose, in concentration
of 1-2%
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45. Binder45
Ensure that granules and tablets can be formed with
the required mechanical strength ( glue that holds
powders together to form granules ).
Eg- starch paste
Glucose
Gelatin solution
Acacia
Sucrose
46. Incorporation of binder
1. Dry Powder
As dry powder mixed with other ingredient before wet
granulation
As a dry powder in dry granulation (roller compaction,
slugging)
2. Solution binder
As a solution in wet granulation.
Binder can be added either dry with other excipients for
granulation or
Already dissolved in the granulating fluid;
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47. Typical binder concentration is 2 – 10% by
weight
Binders can be:
Insoluble in water, e.g. starch
Soluble in water e.g. HPMC
Soluble in water and ethanol e.g.Povidone
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48. LUBRICANT
Lubricants prevent adherence of
granule/powder to die wall and to
promote smooth ejection from the die
after compaction.
Mechanisms of Action :
1. Fluid lubrication.
2. Boundary lubrication.
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49. 1. Fluid lubrication
A layer of fluid is located between the moving surfaces
separating them from each other & thus reduces the friction,
e.g. liquid paraffin.
2. Boundary lubrication:
The sliding surfaces are separated by only a very thin film of
lubricant.
So, the nature of the solid surfaces will therefore affect
friction.
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50. Disadvantages of lubricants
1. Lubricants tend to be hydrophobic.
Under-lubricated blends tend to flow poorly and show
compression sticking problems
Over-lubricated blends can adversely affect tablet hardness
and dissolution rate, as well as tablet strength.
Eg:
Magnesium Stearate
Calcium Stearate , Talc
Stearic Acid
Sodium Lauryl Sulfate, liquid Paraffin, propylene glycol, (PG)
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51. Glidant or flow aid
Improve flowability of the powder
added during direct compaction and to granulation
before tableting ( they reducing interparticulate
friction).
Common Glidants are
1. Talc ( at concentration 1-2 % ).
2. Colloidal silica ( 0.2 %
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52. Antiadherent
Reduce adhesion between the powder and the
punch faces & thus prevent particles sticking to
the punches; due to excess moisture or
engraved and/or embossed punch face.
Many lubricants, such as magnesium stearate,
have also antiadherent properties.
Also talc and starch can act as antiadherents.
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53. Sorbent
Are substances that are capable of
sorbing some quantities of fluids in an
apparently dry state.
Thus, oils or oil-drug solutions can be
incorporated into a powder mixture
which is granulated & compacted into
tablets.
e.g. Microcrystalline cellulose & silica.
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54. Flavor
Give the tablet a more pleasant taste or to
mask an unpleasant one.
Flavoring agents are often thermolabile and
so cannot be added prior to an operation
involving heat.
They are often mixed with the granules as
an alcohol solution.
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55. Colourent
It is added to tablets to aid identification and
patient compliance.
added during coating.
It can also be added prior to compaction. ( can
be added as an insoluble powder or dissolved in
the granulation liquid. )
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56. Sweeteners
They are used in chewable tablet to exclude
or limit the use of sugar in the tablets.
Mannitol, 72% as sweet as sucrose.
Saccharin, 500 times sweeter than sucrose.
Disadvantage
has a bitter taste after some time and
carcinogenic.
Aspartame, Largely replace saccharin.
Disadv.: Lack of stability in the presence of
moisture.
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58. Tablet Compression Machine
Hopper for holding and feeding granules or
powder to be compressed.
Dies that define the size and shape of the tablet.
Punches for compressing the granules within
the dies.
A feeding mechanism for moving granules
from the hopper into the dies.
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61. Stages of Tablet Formation
(Compaction Cycle)
Gravitational flow of the powder from hopper via the die table
into the die .
(the die is closed at its lower end by the lower punch).
Tablet formation
The upper punch descends , enters the die ,the powder is
Compressed until a tablet is formed.
After maximum applied force is reached,the upper punch
leaves the powder.
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62. Tablet ejection
The lower punch rises until its tip reaches
the level of the top of the die.
The tablet is subsequently removed from the
die and die table by a pushing device.
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64. Single Punch press (Eccentric Press):
Bench-top models that make one
tablet
At a time (single-station presses)
Disadvantages: production of small
batches of tablets
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65. Rotary Press( Multi station Press):
(10 000 tablets per minute)
Large scale production.
It consists of a number of dies and sets of punches (
from 3 up to 60).
The dies are mounted in a circle in the die table
both the die and the punches rotate together during
operation of the machine.
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67. 67
The powder is held in a hopper whose lower
opening is located just above the die table.
The powder flows on to the die table & fed into the
die by a feed frame.
During powder compression both punches operate
by vertical movement.
After tablet ejection, the tablet is knocked away as
the die passes the feed frame.
68. Reference
Text book of physical pharmacy by Tripathi pg no 210-263.
Sherwood BE & Becker JW (1998) “A new class of high-
functionality excipients: silici-fied microcrystalline cellulose”
Pharm Tech 22 78–88.
Vogel, P.J.; Schmidt, P.C. Force –Time Curves of a Modern
Rotary Tablet Machine. II. Influence ofCompression Force and
Tableting Speed on the Deformation Mechanisms of
Pharmaceutical Substances. Drug Dev. Ind. Pharm. 1993, 19,
1917.
The theory and practice of industrial pharmacy fourth edition
by lachman/lieberman page no 449-543
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