Sei sulla pagina 1di 190

Solid Oral Dosage Forms

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.

• They are used for local &


systemic effect.

• Usually used for oral administration.


Tablets are popular due to:

1. A convenient and safe way of drug


administration.

2. Compared to liquid dosage form they are


more physically & chemically stable.

3. Enables more accurate dosing.


4. Convenient to handle and can be
prepared in different ways according to
their use.

5. They can be mass produced ,


with quality-controlled production
procedures giving an elegant
preparation of consistent quality
and low price.
Disadvantages of tablet:
1. It’s not suitable for poorly water-soluble
or poorly absorbable drugs less
bioavailability.

2. Enhances local irritant effect of some


drugs or cause harm to the
gastrointestinal mucosa.

3. Some drugs resist compression


into dense compacts.
Quality attributes of tablets:
1. The tablet should include the correct dose
of the drug.

2. The appearance of the tablet should be


elegant and its weight, size
and appearance should be
consistent.

3. The drug should be released


from the tablet in a controlled
and reproducible way.
4. The tablet should be biocompatible .

5. The tablet should be of sufficient


mechanical strength to withstand
fracture and erosion during handling.

6. The tablet should be


chemically, physically and
microbiologically stable
Tablet types
Compressed Tablet
• Un-coated
• Inunediate Release
Tablet Manufacturing
Tablet Compression Machine
• Design:
1. Hopper for holding and feeding granules or
powder to be compressed.
2. Dies that define the size and shape of the
tablet.
3. Punches for compressing the
granules within the dies.
4. Cam tracks for guiding the
movement of the punches.
5. A feeding mechanism for
moving granules from the
hopper into the dies.
Tablet tooling; punches and dies
Tablet machine or tablet press
1,>pp er-----

anules�---�•
Eccontrlo
Clln"I

l.owc:ir punch

Pl notion
roguhHlllg
oollur
....,...,....,...,...C"'C".....:iF--,.,"""" --Lift
(oouplad to a
I no block com
drive on tho
shoftl
-Weight
rc:,gul oll na
coll or
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

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.
The compression cycle for a single
punch tablet machine
First stage Second stage Third stage
Hopper

1',.
Lower punch holder
Collection and filling Compression Ejection
f!'llo,_.1,on "1
Ut:>,>ef'r:,....--..r. lb- .-e,.e.,-1.
tow.-..- punch "'-• ar,o.pped

Poaltton 2
MC>Pi:t<ef" •hc:,.e, t-..- rr�
tnl'Wlll....-t ...,._,. --Rn�,
ora.nutea ta.II lnt-o cue

Po•t1Jon ::,
M�r ......._.,,.....,. �.,.,.,
h•r.k lJf"r-r ,.,...-�J"I hAA
com• <Jowf't corn�••••no
gro-ufc:,• tnlo 10.bf.ol
�.. ,tlr•n •
uoc:,,e, puncn naa mOY'ot)O
-.,o--.rct• �r pvn,ch
t •If� ,,.� v....-,'-'4 tv
••I� t.1"110f•.._I Tt-... ey,ot�
IA l"'t<DW .....�t..,C,

Hopper ..hoe

Dk>
Lowe,. punch

Ejecuon regutaung screw

- Cspec,1y re,;iulat,ng screw


Stages of Tablet Formation
(Compaction Cycle)
1. Forcing particles into close proximity to
each other by powder compression.
2. Compression takes place in a die by the
action of two punches (lower & upper).
Powder compression
The reduction in volume of a powder
owing to the application of a force.
compaction
The formation of a porous specimen of
defined geometry by powder compression.
Tablet Presses
• Single Punch
• Rotary Press
• High Speed Rotary Press
• Multi-layer Rotary Press
1. 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
(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.

• 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 and both the die table &
the punches rotate together
during operation of the machine.
Rotary Press Machine
Rotary Press Machine
• 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.
Uppe, Lowerlno Cam Upper Llftino Cam
Soaper end Ta� Over Doe

We,gllt Conltol U,.t


Tablet Ingredients (excipients)

• 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.

• The common types Filler

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

• First: The liquid wets the solid and


penetrates the pores of the tablet the
tablet breaks into smaller fragments
(aggregates of primary particles).

• Second: The aggregates will


deaggregate into their primary
powder particles.
Mode of action:
1. Facilitate water uptake into the pores of tablet,
e.g. surface active agents
2. Facilitate rupture of tablet by swelling during
water sorption,
e.g. starch, modified cellulose
3. Release of gases to disrupt the
tablet structure, normally
carbon dioxide, in contact
with water. e.g. effervescent
tablets.
4. Recovery of deformed particles to their original
shape in contact with water.
The Method of Disintegrant Addition:
1. Mixed with other ingredients prior to
granulation & thus incorporated within the
granules (intragranular addition).

2. Mixed with the dry granules before the


complete powder mix is compacted
(extragranular addition).

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.

• Many lubricants, such as


magnesium stearate, have
also antiadherent properties.
Also talc and starch can act
as antiadherents.
• Def.: 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.
• Give the tablet a more pleasant taste or to
mask an unpleasant one.

• Flavouring 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.
• It is added to tablets to aid identification
and patient compliance.

• It is added during coating.

• It can also be added prior to


compaction. (can be added as an
Insoluble powder or dissolved in the
granulation liquid).
• They are used in chewable tablet to exclude or
limit the use of sugar in the tablets.
e.g. Mannitol, 72% as sweet as sucrose.

Saccharin, 500 times sweeter than


sucrose. Disadv.: has a bitter taste after time
and carcinogenic.

Aspartame, Largely replace saccharin.


Disadv.: Lack of stability in the
presence of moisture.
The Tablet Manufacturing Process
• The tablet manufacturing process is the step
by step, individual operations required to
make powders into a tablet.

• This is known as individual units of operation;


or commonly referred to as
Unit Operations.

• Weighing, Blending and Tableting


are unit operations in the tablet
manufacturing process.
The Tablet Manufacturing Process
• Powders must Flow and Compress in order to
make a good tablet.

• We may need to add many unit operations to


make the powders perform.
• Each different formula may have a
different number of unit operations,
which is based completely on the
ability to Flow and Compress and
then eject from the tablet press.
• Tablets are prepared either by:
• Pre-granulation.
• Direct compression

• 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.

• It is important to control particle size


distribution of the granules,
why???
Granulation overview
• A process of size enlarging a mix of active
ingredient and excipient powder particles into
stable aggregates exhibiting desired
properties of:
• Compressibility
• Cohesiveness
• Flowability
• Bulk density
• Granules may be a final product
or an intermediate product that
needs further processing
Primary powder
particles

adhere

Granules
(larger free flowing multiparticles)
• Granules size 0.2 - 4 mm (depending on the use)

• Intermediate product • Larger granules


(In tablets & capsules (When used as a Dosage form)
production) typical size
is 0.2-0.5mm.
Granulation Steps
- Initial dry mixing of powdered
ingredients (to achieve uniform
distribution of each ingredient
through the mix.).

- Granulation.

- Mixing with other excipients prior to


tablet compaction or capsule filling).
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 e.g water,
ethanol.
• The granulating solvent may contain a
binding agent to ensure particle
adhesion after drying.
Tablet Production via Wet Granulation:
Process description:
• Agitation of a powder by convection in the
presence of a liquid.

• It forms the granules by binding the powders


together with an adhesive.

• Once the granulating liquid has been


added, mixing continues until uniform
dispersion is attained (15 min. to an hour).
The mass should merely (just) become
moist rather than wet or pasty (there is a
limit to the amount of solvent that may be
employed).
- Overly wet material would block the
screens & prolong the drying
processing.
• 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.
• The moist mass is broken up into coarse,
granular aggregates (using screens with large
perforations).
• The purpose is to increase surface area to
facilitate removal of moisture.
• Sreening the dry granules
• Mixing with other tablet excipients
(lubricant, glidant, remaining of
disintegrant) and then compaction.
Mixers and Blender

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

• A process of evaporating the liquid


contained within aggregates
produced by a wet granulation
process to a predetermined moisture
content
• Accomplished via direct (tray dryer)
or indirect (fluidized bed dryer)
contact of the product with the
heating medium
Tray dryer Fluid bed dryer
Single Step Technology for Wet
Granulation
• Single machines utilized for both the
wet granulation and drying process in
one unit operation.
• Use Fluid Bed Dryer (FBD)
• It is a multiple step process performed
in the same vessel to mix, granulate
and dry the powders.
• Combines wetting the powders to
form granules &then, drying them in
the same piece of equipment.
Advantages of FBD
• Reduced product handling
• Closed process suitable to:
� Potent compounds
Minimizing product/operator
� exposure
� Minimizing cross contamination and
product loss
� Reduced cleaning and overall
process time
• Reduced equipment and floor space
requirements
FBD

• Powder bed is fluidized


for dry mixing and is
wetted with an
agglomeration solution
introduction as a fine
mist.
• The agglomerated
material remains
fluidized during hot air
drying
Spray Drying
• Best granules, regarding homogeneity,
flowability and compactability.
• The tablet components are suspended
/or dissolved in a suitable vehicle
according
to their nature.
• The slurry is pumped to an atomizing
wheel which whirls the material into a
stream of hot air Under constant stirring
to maintain good distribution.
• The heat removes the liquid carrier and
the solids fall to the bottom of the dryer
as a fine spherical granulate (10 – 250
µm).
Steps of granule (agglomerate)
formation by FBD
Tablet Produced by Compression
Granulation (Dry Granulation):
• Advantage:
(1) Avoid exposure of the powder to
moisture and heat.
(2) Used for powders of very low
bulk density to ↑ their bulk density.

• 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

Slugging Roller Forced through a


compaction sieve
To produce a
Powder is Wet granules
large tablet
(slug) in a squeezed drying
heavy duty between 2
tabletting rollers to Dry granules
press produce a
sheet of Screening stage
material
Break agglomerates of
granules & remove fine
Intermediate product particles.
Intermediate product • The fluid contains a solvent, which
must be :
broken 1. volatile so that it can be removed
(suitable by drying.
milling 2. be non-toxic.
technique) Typical liquids include:
1. water : may adversely affect drug
Granular material stability, causing hydrolysis ,it
needs a longer drying time. This
sieved increases the length of the
process. The advantage :non-
flammable and economic.
Separate the 2. Ethanol, Isopropanol ,or
desired size combination (organic solvents)
used with water sensitive drugs
fraction. ,alternative to dry granulation or
when rapid drying time is
required.
• It involves only two unite operations
powder mixing and tabletting.
• Advantages of Direct Compaction:
1. Reduced production time &cost.
2. Product stability can
be improved.
3. Faster drug dissolution due to fast
disintegration into primary particles.
Disadvantages of Direct Compaction:
1. Large particles must be used → (acceptable
flowability and bulk density)

2. If the drug powder has low compactabilty, it is


difficult to form into tablets.

3. Needs directly compressible filler that


is usually expensive, e.g. microcrystalline
cellulose (Avicel), spray dried lactose.
• Drugs used in Direct Compaction:
1. Soluble drugs which can be processed as
coarse particles (to ensure good flowability).
2. Potent drugs which are present in a few
mgs in each tablet (mixed with relatively
coarse excipient particles).
Steps of Tablet Production by Direct
Compaction:
- Drug
- Filler
+

• Dry binder Tableting


• Disintegrant
• Lubricant

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:

BINDING Chipping &


Cracking
1. Binding:
It is the adhesion of the granules to the die wall
and this cause the resistance of the tablet to
eject from the die, it is usually due to insufficient
lubrication, which produce tablets with rough
and vertical score marks on the edges.

• 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:

Capping occurs when the upper


segment of the tablet separates from the
main portion of the tablet & comes off as
a cap.
• It is usually due to air entrapped
in the granulation which is
compressed in the die during the
compression & then expands
when the pressure is released.
• Reasons of capping : 1. large amount of fines in
the granulation &/or the lack of sufficient
clearance between the punch and the die wall.
2. In new punches and dies that are tight fitting.
3. Too much or too little lubricant or excessive
moisture.

Lamination is due to the same


causes as capping except that
the tablet splits at the sides into
two or more parts.
If tablets laminate only at certain
stations, the tooling is usually the cause.
• Solutions for capping & laminating:

1. Increasing the binder.


2. Adding dry binder such as gum acacia ,
PVP or powdered sugar.
3. Decreasing the upper punch
diameter.
4. Mottling:
It is an unequal distribution of color on the surface
of the tablet.
• Cause : 1. A drug that differs in color from its
excipients or whose degradation products
are highly colored.

2. Migration of a dye during drying


of a granulation (change the solvent
system, reduce the drying temperature,
or grind to a smaller particle size).
Tablets Types
• Tablets can be classified according to 0
their drug-release characteristics into:
Immediate-release tablets
The drug is intended to be released rapidly
after administration, or the tablet is
dissolved and administered as a solution.
This is the most common type of tablet &
includes disintegrating, chewable,
effervescent, sublingual & buccal
tablets.
Modified-release tablets
- Should normally be swallowed intact.
- Different excipients than
immediate release tablets.
The drug is released from an extended-release
tablet slowly at a nearly constant rate.
Delayed-release tablets
The drug is liberated from the tablet some time
after administration.
After this period has elapsed, the release is
normally rapid.
e.g. Enteric tablet, for which the drug is
released in the upper part of
the small intestine after the
preparation has passed the stomach.
A delayed-release can also be
combined with a slow drug release, e.g.
for local treatment in the lower part of
the intestine or in the colon.
Tablet types

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.

Tablet Drug Drug


disintegration dissolution absorption

Steps of drug release from disintegrating tablets


2. Chewable tablets
• They are chewed so mechanically disintegrated in the
mouth.
• The drug is not dissolved in the mouth but swallowed
and dissolves in the stomach or intestine.
Uses of chewable tablets:
1. Quick and complete disintegration of the tablet - and
hence obtain a rapid drug effect e.g. antacid tablets.
2. Facilitate the intake of the tablet for elderly and
children who have difficulty in swallowing e.g. vitamin
tablets.
3. Can be taken when water is not available.
They are similar in composition to conventional tablets
except that a disintegrant is normally not included.
3. Effervescent tablets
Effervescent tablets are dropped into a glass of water
before administration, during which carbon dioxide is
liberated.

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.

Dissolution of buffered water temporarily


tablets solution increases the pH
of the stomach.
rapid emptying
fast drug bioavailability of the stomach
(As drugs are absorbed and shortening
more effectively in the the residence
small intestine than in the time
stomach) e.g.
analgesics Drug-induced gastric irritation can
be avoided (due to short residence
time) e.g. aspirin tablets
Effervescent tablets usually
contain

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:

They must be protected against moisture by using


waterproof containers, often including blister packs or
aluminium foils, otherwise it will be self destructed.
4. Lozenges
• They are tablets that dissolve slowly in the
mouth and so release the drug dissolved in
the saliva.
• They can thus be described as slow-release
tablets for local drug treatment.
Use of lozenges:
Local medication in the mouth or throat in
common cold, to treat cough by
1. local anesthesia,
2. antiseptic
3. antibiotic drugs.
Lozenges are usually contain:
1. They are similar in composition to conventional
tablets.
2. Disintegrants are not used.
3. Colour and flavour.
4. High concentration of Fillers which are mainly sugars,
such as glucose, sorbitol or mannitol.
5.High concentration of binder; e.g. gelatin.
Lozenges are prepared by

Compaction at high applied pressures in order to


obtain a tablet of high mechanical strength and low
porosity which can dissolve slowly in the mouth.
5. Sublingual and buccal tablets
• Used for drug release in the mouth followed
by systemic uptake of the drug.
• Rapid systemic drug effect can thus be
obtained without first-pass liver metabolism.
• Sublingual tablets are placed under the
tongue and buccal tablets are placed in
the side of the cheek.
• They are often small and porous, the latter
facilitating fast disintegration and drug
release.
6. Soluble tablets

• Soluble tablets are uncoated or


film-coated tablets. They are
intended to be dissolved in
water before administration. The
solution produced may be
slightly opalescent due to the
added excipients used in the
manufacture of the tablets.
• This test may be official or unofficial.

• Official tests are:


1. Weight variation 2. Content uniformity
3. Dissolution. 4. Disintegration.

• Non official tests are:


1. Friability .
2. Hardness. 3.Thickness .
1. Weight Variation:
• Collecting a sample of tablets(normally 20)
and determining their individual weights.
• The average weight of the tablets is then
calculated.
• The sample complies with the
standard if the individual weights
don’t deviate from the mean more
than is permitted in terms of
percentage.
Ranges in which weigh deviation is
accepted:
• If the drug forms the greater part
of the tablet mass, any weight
variation reflects variations in the
content of active ingredients.

• In case of potent drugs, the


excipients from the greatest part
of the tablet weight & so the
correlation between tablet
weight and amount of active
ingredient can be poor.
• What is the significance of the
weight variation test????

• If tablet batch not pass the test,


what processing factors are the
cause for such Failure?? And
what is the possible solution????
Causes of Weight Variation:
1. The size & distribution of the granules being
compressed (presence of too large or too fine
granules).
2. Poor flow (cause incomplete filling of the die).
3. Poor mixing. (Sometimes the lubricants & glidants
have not been well distributed).
4. When lower punches are of
unequal lengths the fill of each
die varies because the fill is volumetric.
Solution: (Only a good punch & die
control program can provide tooling
of uniform dimensions). Change lubricate and/or
glidant.
2. Content Uniformity:
• Determining the amount of drug in a sample of
tablets (10 ).
• The average drug content is calculated.
• The content of the individual
tablets should fall within
specified limits in terms of % deviation
from the mean (85 – 115%). If not comply
repeat using 20 more tablets.
No one should be 75 – 125% deviation
Causes: ???
Solution: ????
3. Disintegration:

The test is carried out by:


• Agitating a given number of tablets in an aqueous
medium at a defined temperature & the time to
reach the end-point of the test is recorded.
• The end-point of the test is the
point which all visible parts of the tablets
have been eliminated from tubes in which
the tablets has been held during agitation.

• The preparation complies with


the test if the time to reach this
end-point is below given limit; 15-30 minutes for
uncoated immediate release tablets.
The disintegration basket
A disintegration apparatus
• Special cases
• Effervescent tablets

• Place 1 tablet in a beaker


containing 200 ml of water at 25°C;
the tablet should evolve bubbles
and disintegrate within 5 minutes,
use 6 tablets
• Soluble tablets

• Soluble tablets disintegrate within 3


min when placed in water at 25°C.
• Sugar coated tablets???

• Enteric coated Tablets????


• What is the significance of
the disintegration test???

• If tablet batch not pass the


test, what processing
factors are the cause for
such failure?? And what is
the possible solution???
4. Dissolution:

• It is an important tool to assess


factors that affect the
bioavailability of a drug from
a solid preparation.
• Dissolution tests are carried out for several
reasons :

1. To evaluate the possible effect of


formulation & process variables on the
bioavailability of a drug.

2. To indicate the performance


of the preparation under in vivo
conditions.
• The Dissolution test:
• To study the cumulative amount of drug
that passes into solution as a function of
time.
• Locate the tablet in a chamber
containing a flowing dissolution medium.
• All factors that can affect the dissolution
process must be standardized.
This includes factors that affect
the solubility of the substance
(i.e. the composition, rotation &temperature of
the dissolution medium)
• Dissolution tests can be classified into
two main groups:
1. Stirred-vessel methods.
2. Continuous-flow methods.

• The most important Stirred Vessel


methods are:
1. Rotating-basket method (Apparatus I).
2. Paddle method (Apparatus II).
The dissolution test apparatus
Paddle Rotating Basket
Method Method
Both use the same type of vessel, which is filled
with a dissolution medium of controlled volume
and temperature.

The tablet is placed in The tablet is placed in a


the vessel & the small basket formed
dissolution medium is from a screen. This is
agitated by a rotating then immersed in the
paddle. dissolution medium
& rotated at a given
speed.
(1) (2)


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.

- Tablet hardness should be between


6 – 10 kg
. Hardness Variation:
• It depends on:
- compression force,
- concentration and type of binding agent
• If the tablet initially is too hard, it may not
disintegrate in the requisite period of time.
• If it is too soft, it may not withstand
the necessary multiple shocks
occurring during handling,
shipping, and dispensing.

• N.B. Hardness generally increase with


normal storage of tablets.
2. Friability (attrition-resistance test):
It's another measure of a tablet's strength.

Why measure friability?


Tablets that tend to powder, chip &
fragment when handled:
1. lack elegance & consumer acceptance,
2. Create excessively dirty
processes in areas of manufacturing as
coating & packaging.
3. Can also add to a tablet's weight
variation or content uniformity problems.
• The laboratory friability tester is known as the
Roche friabilator.

• It subjects a number of tablets to the


combined effects of abrasion & shock by
utilizing a plastic chamber that revolves at 25
rpm, dropping the tablets with each
revolution.

• A preweighed tablet sample is


placed in the friabilator, which is
then operated for 100 revolutions.
The Roche friabilator
Tablets damaged during friability testing
• Tablets are then dusted and reweighed.

• Conventional compressed tablets that


lose less than 1.0% of their weight are
generally considered acceptable.

• % friability = (W0 – Wf / W0) x %.


W0 = initial weight.
Wf = final weight.
3. Tablet's Thickness:

• Thickness can vary with no change in


weight due to difference in the density of
the granulation & the pressure applied to
the tablets.

• If the tablets are thicker than


specified, a given number no longer
may be contained in the volume
of a given size bottle.
TABLET COATING
What is the rationale for coating a solid
dosage form?

Therapy
• To minimise irritation of the oesophagus and stomach.

• Minimise inactivation in the stomach.

• Improve drug effectiveness.

• Improve patient compliance e.g. easier to swallow,


masks unpleasant taste.
What is the rationale for coating a solid
dosage form?
Technology
• Minimise dust formation and contamination with respect
to tablets.

• Masks batch differences in the appearance of raw


materials.

• Facilitates their handling on high speed automated filling


and packaging equipment.

• Improves drug stability e.g. Protection of active ingredient


from environment such as sunlight, moisture.
What is the rationale for coating a solid
dosage form?
Marketing
• Aid sales appeal as improved
appearance and acceptability with
respect to gloss and colouration.

• Mask unpleasant taste.

• Improve product identity.


Definition
• Coated tablets are defined as
tablets covered with one or
more layers of mixture of
various substances with the
intention of (adding) conferring
benefits and properties to the
dosage form over the
uncoated one.
Main coating processes

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.

3. Smoothing process -remove rough layers formed in step


2 with the application of sucrose syrup.
Multistage process

4. Colouring - for aesthetic purposes often titanium based


pigments are included.

5. Polishing - effectively polished to give characteristic


shine, commonly using beeswax, carnauba wax.

6. Printing -permanent ink for characterization.


Sugar coating Pans (drum coating)
Example of sugar coated tablets

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

Spraying Wetting/distribution Recrystallisation Sugar coated particle

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.

• Process: Single stage process, which involves spraying a coating


solution containing the following;
1. Polymer
2. Solvent
3. Plasticizer
4. Colourant
The solution is sprayed onto a rotating tablet bed followed
by drying, which facilitates the removal of the solvent
leaving behind the deposition of thin film of coating
materials around each tablet.
Film coating

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

The vast majority of film coated tablets are produced by a process


which involves spraying of the coating material onto a bed of tablets.
Accela Cota is one example of equipment used for film coating.
Film Coating by Fluidized bed
Mechanism of Film Formation

latex particles dispersed


in liquid vehicle

formation of thin film with


water evaporation through film

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.

Water insoluble pigments are more favourable than


water soluble colours for the following reasons;
 Better chemically stability in light
 Optimised impermeability to water vapour
 Better opacity
 Better covering ability
Solvents
Traditionally, organic solvents had been used to
dissolve the polymer but modern techniques rely on
water because of significant drawbacks. Below lists
some of the problems associated with organic
solvents.

• Environmental
• Safety
• Financial
• Solvent residues
Solvents

1.Environmental

Venting of untreated organic solvent vapour


into the atmosphere is ecologically
unacceptable but removal of gaseous waste
matter is expensive.
Solvents

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

For a given process the amount of residual


organic solvent in the film must be
investigated. Thus, stringent regulatory
controls exist.
Ideal characteristics of film-coated tablets

• Even coverage of film and


colour,
• No abrasion of tablet edges,
• Logos and break lines should be
distinct and not filled,
• Comply with the pharmacopeial
requirement.
Problems of Film Coating

• 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

Press coating process involves compaction of coating material around a preformed


core. The technique differs from sugar and film coating process.
Advantages
This coating process enables incompatible materials to be formulated together, such
that one chemical or more is placed in the core and the other (s) in the coating
material.
Disadvantages
Formulation and processing of the coating layer requires some care and relative
complexities of the mechanism used in the compressing equipment.
Functional coatings

Functional coatings are coatings, which perform a


pharmaceutical function.

These include;
• Enteric coating

• Controlled release coating


Enteric coating
The technique involved in enteric coating is protection of the
tablet core from disintegration in the acidic environment of the
stomach by employing pH sensitive polymer, which swell or
solubilize in response to an increase in pH to release the drug.

Aims of Enteric protection:


 Protection of active ingredients, from the acidic environment of
the stomach.
 Protection from local irritation of the stomach mucosa.
 Release of active ingredient in specific target area within
gastrointestinal tract.
Enteric coating
• An enteric coating is a barrier
applied to oral medication that
controls the location in the
digestive system where it is
absorbed.
• Enteric refers to the small
intestine, therefore enteric
coatings prevent release of
medication before it reaches
the small intestine.
• used for drugs that are
unstable, irritating to stomach
Examples of enteric coated OTC products

• Enteric coated aspirin E.g.


Micropirin® 75mg EC
tablets

• Enteric coated peppermint


oil E.g. Colpermin®
Summary of Polymers used in pharmaceutical formulations
as coating materials.

Polymer Trade name Application

Shellac EmCoat 120 N  Enteric Coatings, pH 7


Marcoat 125  targeting to distal small
intestine
Cellulose acetate Aquacoat CPD®  Enteric Coatings
phthalate Aquacoat® ECD  Sustained release coating

 Sub coat moisture and


barrier sealant pellet coating
Polyvinylacetate Sureteric®  Enteric Coatings

phthalate

Methacrylate Eudragit®  Enteric Coatings


Sustained Release Coatings
Rapidly disintegrating Films
Film coating of Beads and
spheres
• Fluid bed dryer is used