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PRASHANT PANDEY
M.Pharm (Pharmaceutics)
C.S.J.M University, Kanpur
mrpandeyprashant@gmail.com
FORMS
• Powders
• Pills
• Troche
• Capsules
• Tablets
• Convenient
• Relatively Stable
• Easily Administered
• Palatable
• Flexible
• Tablets: Solid preparations each containing
a single dose of one or more active
ingredients and obtained by compressing
uniform volumes of particles.
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Stages of Tablet Formation
(Compaction Cycle)
Die filling
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.
Tablet ejection
1',.
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Collection and filling Compression Ejection
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Disadvantages: Production of
small batches of tablets
(200 tablets per minute).
2. Rotary Press( Multi station Press):
• It was developed to increase the output of
tablets (10 000 tablets per minute), used for
Large scale production.
• The powder flows on to the die table & fed into the
die by a feed frame.
• Active • Non-Active
- Drug Substance - Diluents
- Binders
- Lubricants
- Disintegrants
- Coloring
- Flavoring
- Antiadherents
- Glidants
(
'··-=---->
Tablets Excipients
• Their role: To ensure that tablets of
specified quality are prepared.
of tablet’s excipients
are described in the
Binder
figure. Disintegr
ant
Glidant
Anti-
Flavor
adherent
Colorant
&
Lubricant Sorbent
Sweetene
rs
• Use: Increase the bulk volume of the
powder and hence the size of the tablet
suitable for handling .
Therefore, is not necessary if the dose of
the drug per tablet is high.
• 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.
• Requirements for a good filler:
1. Chemically inert, biocompatible, cheap.
2. Non-hygroscopic.
3. Good biopharmaceutical properties.
(water soluble or hydrophilic).
4. Good technical properties
(compactability )
5. Have an acceptable taste.
• Role: To ensure that the tablet, when in
contact with a liquid, breaks up into
small fragments, which promotes rapid
drug dissolution.
Steps of the disintegration process
3. Incorporated as both an
intragranular and an extragranular
portion.
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%
Starch
• The typical concentration range of
starch in a tablet formulation is up to
10%.
• Mode of Action:
1. Starch particles swell in contact
with water and this swelling can
subsequently disrupt the tablet.
2. Facilitate disintegration by
particle-particle repulsion.
• Role: Ensure that granules and tablets
can be formed with the required
mechanical strength ( glue that holds
powders together to form granules ).
• Starch Paste
• Glucose
• Gelatin Solution
• Acacia
• Sucrose
• Sodium Alginate
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; water is the most
common granulating fluid, very occasionally in a co-
solvent system with, e.g. ethanol.
• 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
• Role:
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.
• 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.
Disadvantages of lubricants
• 1. Lubricants tend to be hydrophobic, so their
levels (typically 0.3 – 2%) need to be
optimised:
– 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.
– To overcome these problems;
- optimum conc. < 1%
- Addition of SAA
- order of mixing, in the last step
Commonly used Lubricants
• Magnesium Stearate
• Calcium Stearate
• Talc
• Stearic Acid
• Sodium Lauryl Sulfate, liquid
Paraffin, propylene glycol
(PG)
• Role: Improve flowability of the powder &
added during direct compaction and to
granulation before tabletting ( they reducing
interparticulate friction).
• Common Glidants:
1. Talc ( at concentration 1-2 % ).
2. Colloidal silica ( 0.2 %
• Role: 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.
• Granulation:
– Wet granulation
– Dry granulation
Reasons for granulating powders before
Tabletting:
1. Increase the bulk density of the powder.
2. Improve powder’s flowability, i.e. uniform
die feed.
3. Reduce segregation .
4. Improve powder’s compactability
by adding a solution binder.
5. Avoid the hazard of generation of
toxic dust.
6. Avoid caking of hygroscopic
powder on storage.
Segregation
• Segregation (demixing) is due to:
1. Differences in size.
2. Differences in density of the components of the mix.
N.B.The smaller &/or denser particles at the base of the
container & larger &/or less dense ones above them.
• Ideal granulation : each granule will
contain all the constituents of the mix.
in the correct proportion.
adhere
Granules
(larger free flowing multiparticles)
• Granules size 0.2 - 4 mm (depending on the use)
- Granulation.
Planetary Mixer
• Good horizontal mixing
• Cross contamination risk
• Poor vertical mixing
WET GRANULATION STEPS
Wet Granulation Manufacturing Steps
Weighing
Mixing
Granulation
Screening
Drying
Screening
Lubrication
(
Compression
Drying process
• Disadvantages:
– Tablet disintegration and dissolution
may be retarded due to double
lubrication and compaction
Steps of Dry Granulation:
• The blend of finely divided powders is
forced into the dies of a large capacity
tablet press.
• Then, compacted by means of flat faced
punches (Compacted masses are called slugs
and the process is slugging) or roll
compactor to produce sticks or
sheets.
• Slugs or sheets are then milled/screened
to produce granules (flow more than
the original powder mixture).
Roller compactor
Dry granulation Wet granulation
Primary powder particles Mix of dry primary powder particles
aggregated under high
pressure. Granulating fluid
(solvent)
Wet mass
Mixing
N.B.
Every granulation should start with
materials that have been ground to the
same approximate particle size, so that
they will blend uniformly in the mixing
step.
Technical problems during tabletting:
• Solution:
• 1. Increasing lubrication.
• 2. Improve lubricant distribution.
3. Increasing the moisture content
of the granulation.
2. Sticking, Picking & Filming:
Adhesion of the material to the punch faces.
• Sticking : (whole adhesion)
Is usually due to improperly(incorrectly) dried or
lubricated granulation causing the whole tablet
surface to stick to the punch faces → dull,
scratched, or rough tablet faces.
• Picking : (localized adhesion)
Is a form of sticking in which a small
portion of granulation sticks to
the punch face & a portion of the
tablet surface is missed.
Sticking occurs when particles
adhere to the punch face
Picking
Filming: is a slow form of sticking and is largely
due to excess moisture in the granulation.
3. Capping & Laminating:
f1d
Laenps
1. Disintegrating tablets
• Most common type is intended to be
swallowed and release the drug in a relatively
short time after disintegration and dissolution
thus fast & complete drug release in vivo
(conventional or plain tablets).
• A disintegrating tablets include the following
types of excipients: filler (if the dose of drug is
low), disintegrant, binder, glidant, lubricant
and antiadherent.
Carbonate
or
Bicarbonate
Weak acid
(citric) CO2
facilitates tablet
disintegration and drug
dissolution; the dissolution
of the tablet should be
complete within a few
minutes.
Uses of effervescent tablets:
1. Rapid drug action, e.g. analgesic drugs .
2. Facilitate the intake of the drug, e.g. vitamins.
Carbonate or A water-soluble
bicarbonate and lubricant is
a weak acid such preferable in
Flavor and a
as citric or tartaric. order to avoid
colourant a film of a
The amount of
sodium hydrophobic
bicarbonate in an N.B. binder and lubricant on
effervescent disintegrant are the surface of
tablet is often normally not the water after
quite high (about included in the tablet
1g) composition dissolution.
Effervescent tablets are prepared
by:
Compaction via
Direct compaction
granulation;
traditional wet
granulation is rarely
used.
Effervescent tablets
packaging:
•
I I
I
I
Basket type Paddle type
• The amount of drug dissolved within a
certain time period is determined by
taking samples from the dissolution
medium and analyzed after specified
time intervals.
• Limit: 75% of the drug should be dissolved
within 30 minutes, unless otherwise
specified by the manufacturer.
• Mechanical strength
a. Hardness
b. Friability
c. Thickness
1. Hardness (Fracture-resistance test):
Tablets require a certain amount of
strength or hardness. Why?
1. Withstand mechanical shocks of
handling in manufacture, packaging
and shipping.
2. Withstand reasonable abuse
when in the hands of the consumer.
3. The relationship of hardness
to tablet disintegration, dissolution .
• Tablet Hardness: The force required to break a
tablet along its diameter by applying compression
loading.
• Test Description:
A tablet is placed between two anvils,
force is applied to the anvils, & the
crushing strength that just causes
the tablet to break is recorded (in kg).
Hence, Hardness is thus sometimes
termed the tablet crushing strength.
Therapy
• To minimise irritation of the oesophagus and stomach.
1. Sugar coating
2. Film coating
3. Press coating
SUGAR COATING
Sugar coating
• Traditionally sugar coatings formed the bulk of coated tablets but today
film coatings are the more modern technology in tablet coating.
• Description of tablets: Smooth, rounded and polished to a high gloss.
• Process: Multistage process involving 6 separate operations.
1. Seal tablet core
2. Sub coating
3. Smoothing
4. Colouring
5. Polishing
6. Printing
Multistage process
1. Sealing tablet core- application of a water impermeable
polymer such as Shellac, cellulose acetate phthalate and
polyvinyl acetate phthalate, which protects the core from
moisture, increasing its shelf life.
2. Sub coating -by adding bulking agents such as calcium
carbonate or talc in combination with sucrose solution.
Brufen® POM
– Available in 200mg and
400mg strength
Premarin® POM
– Conjugated oestrogens
625mcg (maroon) and
1.25mcg (yellow)
Colofac ® P
– Mebeverine hydrochloride
100mg Round, white,
sugar coated
Simplified representation of sugar
coating process
Particle
Layer build-up
Coating droplets
• Ideal properties of sugar coating
- Perfect smooth rounded countour
- Even colour coverage
- Polish to high gloss
• Coating faults
• Coat splitting caused by inadequate drying of
coat during application
Film coating
• Modern approach to coating tablets, capsules, or pellets by
surrounding them with a thin layer of polymeric material.
• Description of tablets: Shape dictated by contour of original core.
Advantages
Produce tablets in a single step
process in relatively short period of
time. Process enables functional
coatings to be incorporated into the
dosage form.
Disadvantages
There are environmental and safety
implications of using organic solvents
as well as their financial expense.
Accela Cota
Accela Cota
continuous film
Polymer used in film coating
Examples;
• Cellulose derivatives;
Hydroxypropyl
methylcellulose (HPMC), MC,
HPC, water soluble
- Ethylcellulose is water
insoluble
• Methacrylate amino ester
copolymers;
- pH selective polymer
Plasticizer used in film coating
- Reduce film brittleness
- Examples;
• Polyols - Polyethylene glycol
400
• Oils/glycerides - fractional
coconut
oil
Colourants used in film coating
Examples;
• Iron oxide pigments
• Titanium dioxide
• Aluminium lakes.
• Environmental
• Safety
• Financial
• Solvent residues
Solvents
1.Environmental
Safety
Organic solvents are a safety hazard, such that they are:
Toxic
Explosive
Fire hazard
Solvents
Financial
The hazards associated with
organic solvents necessitates the
need for building flame- and
explosive- proof facilities. In
addition, the cost of their
storage and ingredients are
relatively expensive.
Solvents
Solvent residues
• picking/chipping
• roughness
• sticking
• film cracking/peeling
Why is film coating favoured over
sugar coating ?
Film coating Sugar coating
Tablet appearance Tablet appearance
Retains shape of original core Rounded with high degree of
polish
Small weight increase of 2-3%
due to coating material Larger weight increase 30-50%
due to coating material
logo or ‘break lines’ possible
Logo or ‘break lines’ are
impossible
Process Process
Can be automated e.g. Accela Difficult to automated e.g.
Cota traditional coating pan
Easy training operation Considerable training operation
Single stage process Multistage process
Easily adaptable for controlled Not able to be used for controlled
release allows for functional release apart from enteric coating.
coatings.
Press coating
These include;
• Enteric coating
phthalate