16/04/2020

Tableting
- Chapter 9
Part 1

Definition of tablets

Compressed tablets are solid dosage forms prepared by

compaction of a formulation containing the drug substance
(API) and excipients selected to aid processing (such as
lubricant to prevent sticking) and improve the properties of the
product (such as disintegrant).

1
 16/04/2020

Advantages of tablets
Advantages of tablets as a dosage form:
1. Tablets can be produced at a much greater rate than any
other dosage form.
2. Tablet is a dry dosage form thus promoting stability, in
general; tablets have shelf lives measured in years.
3. Tablets are easy to dispense.
4. Tablets are readily portable and consumed dosage form.

Advantages of tablets
5. If property prepared, tablets provide a uniformity of dosage
greater than a liquid medicine.
6. Tables provide a versatile drug delivery system. Whilst most
tablets are intended to be swallowed intact, others may be
used for sublingual and buccal administration.

2
 16/04/2020

Qualities of well prepared tablets

1. It should contain the stated dose of drug within permitted
limits.
2. It should be sufficiently strong to withstand the stresses of
manufacture, transport and handling, so as to reach the
patient intact.
3. It should deliver its dose of drug at the site and at the speed
required.
4. Its size and appearance should not detract from its
acceptability by the patient.

Basic principles of tableting

1. The tablet ingredients (for example powder) are

fed into a dies.
2. Such powder in the is then compressed between
punches.
3. Following this, the compacted mass is ejected
from the die.

3
 16/04/2020

Basic principles of tableting

Thus for a particulate system to be made into tablets, three vital
properties are demanded:
1. The particles must be sufficiently free-flowing → because they
must uniformly flow into the relatively small volume in the die in
a very short time → proving uniformity of weight
2. The particles, when subjected to a force from the punches,
cohere to form a compact of adequate strength (i.e. particles
must be easy to be compressed).

Basic principles of tableting

3. Whilst the particles must cohere, adhesion by the tablet to the
punches and dies must be avoided; otherwise damage to
both tablet and press will occur when attempts are made to
remove the tablet from the die.

Relatively few substances possess these essential properties

without some preliminary treatment.

4
 16/04/2020

Basic principles of tableting

Tablets are produced either by:
a) Direct compression (DC): powder compressed and directly
converted into tablets
b) (Wet or dry) granulation, followed by compression:
1. Powder transformed into granules
2. Granules compressed into tablets

Formulation of tablets
The formulation of a tablet is governed by a number of factors:
1. The drug substance involved, its chemical and physical
properties and route of administration
2. The manufacturing process to be employed (direct
compression vs granulation, followed by compression)
3. The method by which the tablet is to be used, i.e.
swallowed whole, chewed, dissolved in water etc.

5
 16/04/2020

Formulation of tablets: 1. Drug substance

This is the most important consideration for tablet formulation:
It includes the following points:
a) Site and extent of absorption of drug in the gastrointestinal
tract.
b) Stability of the drug to heat or moisture
c) Compatibility of the drug
d) Dose of the drug
e) Solubility of the drug

Formulation of tablets: 1. Drug substance

a) Site and extent of absorption of drug in the gastrointestinal
tract.
If the drug is satisfactorily absorbed in the stomach or intestine,
then a tablet can be designed which is to be swallowed and
which disintegrates in the stomach.
If absorption is (solubility/dissolution-controlled, i.e. poorly
soluble drug), then the particle size of the drug may need to be
reduced, or dissolution promoted in some other way.
If the drug is unstable in gastric fluids, then some form of
protection must be afforded (enteric coating) or it may be
formulated for buccal or sublingual absorption.

6
 16/04/2020

Formulation of tablets: 1. Drug substance

a) Site and extent of absorption of drug in the gastrointestinal
tract.
A similar solution may be adopted for substances which
undergo extensive first-pass hepatic metabolism, e.g.
glyceryl trinitrate sublingual tablets.

Formulation of tablets: 1. Drug substance

b) Stability of the drug to heat or moisture
Substances which would undergo appreciable degradation in
the conditions of the wet granulation process obviously cannot
be made into tablets by this means. In such cases dry
granulation or direct compression must be used, or another
dosage form chosen (i.e. capsule).
c) Compatibility of the drug
The compatibility of the drug with other tablet ingredients in the
solid state, for example magnesium stearate, lactose,
microcrystalline cellulose must be considered, since this will
govern whether these excipients can be used in the production
of the tablet.

7
 16/04/2020

Formulation of tablets: 1. Drug substance

d) Dose of the drug
The dose of the drug will decide the necessity of the filler
(i.e. diluent)→ low potency drug could be produced
without adding a filler.
However…..
If a filler is not used, then there is little possibility of the direct
compression method of tablet preparation being suitable
for this tablets → this is because it is unlikely that the drug
as such will have good enough flow and compaction
properties for undergoing direct compression.

Formulation of tablets: 2. Manufacturing

process
It is a critical importance to choose between direct compression
and granulation (followed by compression). A quick a comparison:
1. Flow:
Granulation improve the flow of powders, proving improved
uniformity of weight for the tablets.
2. Compaction properties:
Granules are more easily to be compressed into hard tablets.
Therefore, for difficult formulations, there is always a clear
advantage in using granulation (followed by compression), rather
then direct compression. However…….

8
 16/04/2020

Formulation of tablets: 2. Manufacturing

process
3. Time
Direct compression involves only two steps: dry mixing of
powdered drug and excipients; compression of the mix.
Wet granulation + compression includes more steps to convert a
drug into a final tablet.
Direct compression is obviously a more rapid overall process.
4. Cost
Direct compression is in theory cheaper, as it involves less steps and
therefore less equipment and less material handling.

Formulation of tablets: 2. Manufacturing

process
Case by case evaluation
The balance between these (and other) aspects determines the
choice between DC and granulation (followed by compression):
 In the rare case of free-flowing, easily to compress powders, direct
compression becomes the obvious choice.
 In case of poorly flowing and/or difficult to compress powder mixes,
one of these two choice should be evaluated:
1. Granulation (followed by compression);
2. Direct compression using special grade of excipients (potentially
very expensive) that can considerably enhance powder flow
and/or compaction properties.

9
 16/04/2020

Formulation of tablets: 3. Tablets type

The formulation will depend also from the method by which the
tablet is to be used, i.e. swallowed whole, chewed, etc.
Hence, depending on the tablet use, different formulation
strategies might be employed.

Formulation of tablets: 3. Tablets type

For example:
1. Conventional immediate release tablet
2. Tablets to be dissolved in water before use
3. Chewable tablets
4. Lozenges
5. Buccal and sublingual tablets.

10
 16/04/2020

Formulation of tablets: 3. Tablets type

1. For the common situation of a tablet designed to disintegrate
after swallowing (i.e. immediate release), and to be made by a
wet granulation process then:
A granulating agent must be chosen to give granules which
compresses to form tablets of acceptable strength.
A lubricant is chosen so as to enable easy ejection from the die.
Care must be taken not to add too much lubricant: this would
both prolong disintegration time and reduce tablet strength.
A sufficient concentration of disintegrant should be used.

Formulation of tablets: 3. Tablets type

2. For tablets to be dissolved in water before use.
An example on solution tablet is the effervescent tablets in which
an acid (usually tartaric or citric acid) reacts with a bicarbonate
(usually sodium or potassium) on the addition of water to
produce carbon dioxide. In such tablets:
a) All ingredients should be soluble
b) The preparation cannot be based on the use of
aqueous-based granulating agent (→ to prevent
effervescence during the granulation process). Hence, a
non-aqueous granulation or a totally dry method of tablet
production is necessary.

11
 16/04/2020

Formulation of tablets: 3. Tablets type

3. For chewable tablets
Chewable tablets are often used for children and geriatric
patients who have difficulty in swallowing tablets.
Since the tablet is not swallowed and it is disintegrated in the
mouth, the taste of the preparation is important in this case.
Taste masking can be achieved by choice of diluent
Taste masking becomes more difficult with drugs of
unpleasant taste, particularly if present in high dose.
→A frequently used diluent is mannitol, which has a pleasant
cooling sensation in the mouth, effectively masking many
taste problems.

Formulation of tablets: 3. Tablets type

4. For lozenges
Tablets that dissolve slowly in the mouth and so release the drug
dissolved in the saliva (e.g. used for local medication of mouth or
throat). Such tablets:
a) Do not contain disintegrants
b) Contain fillers of pleasant taste
c) Must be formulated to obtain hard tablets, so to dissolve slowly
in the mouth.

12
 16/04/2020

Formulation of tablets: 3. Tablets type

5. For sublingual and buccal tablets.
Sublingual and buccal tablets are designed for drug release in
the mouth, followed by systemic uptake of the drug. Drug
absorbed in such way have the advantage of skipping the first
pass metabolism in the liver.
• These tablets should dissolve rapidly. Hence a highly soluble
formulation must be selected (not hard and porous tablets are
often formulated).

Tableting machines (Tablet presses)

Tablets are prepared by compressing a particulate solid in a die
by the application of forces via two punches.

Powder compression is defined as the reduction in volume of a

powder owing to the application of a force. Because of the
increased proximity of the particle surfaces during compression,
bonds are formed between particles which provides coherence
to the powder and a compact is formed.

13
 16/04/2020

Tableting machines (Tablet presses)

Compression sequence
Tablets are prepared by compressing a particulate solid in a die
by the application of forces via two punches.
The punches are termed:
1. The lower punch: the tip of which
moves up and down within the die, but
never actually leaves it.
2. The upper punch, which descends to
penetrate the die and apply the
compressive force and then goes back
up to permit ejection of the tablet.

The die and punches are almost invariably made of hardened

steel.

Tableting machines (Tablet presses)

Compression sequence
Irrespective of the type of tablet press, the process of
compaction can be divided into three distinct stages:
1. The lower punch falls within the die, leaving a cavity into
which particles can flow due to gravity (Filling).
2. The upper punch descends, and the punch tip enters the
die. Further punch movement applies the compressive
force to the particles, which aggregate to form a tablet
(Compression).
3. The upper punch withdraws from the die and simultaneously
the lower punch rises until its tip becomes level with the top
of the die. The tablet is thus ejected from the die and
removed from the tablet press (Ejection).

14
 16/04/2020

Tableting machines (Tablet presses)

Compression sequence
 This process demands that the particulate solid possesses good
flow properties, is coherent, and yet will not adhere to the die
wall and the punches of the press.

Few substances possess all these properties, and so prior

manipulation is almost always necessary.

Tableting machines (Tablet presses)

Tablet presses are of two basic types

1. The single-station or single-punch press.

2. The multi-station rotary press.

15
 16/04/2020

Single punch tablet press

Main Parts
Hopper for holding the granulation
Hopper shoe: it is responsible for feeding the granulation when it
is above the die.
Upper and lower single punches:
 The lower punch
 The upper punch
Die fixed in a disk.

Single punch tablet press

16
 16/04/2020

Single punch tablet press

The hopper shoe, can move on the die disk in a back and forth
motion to be right above the die (during filling) and then back
a way from the die (during compression and ejection).
The output of this type of press is 150-200 tablets per minute at a
maximum, and so its use is limited to relatively small scale
production or development work.

Single punch tablet press - operation

Pre-setting filling volume:
First, before starting the whole compression cycle (filling,
compression, ejection), the weight of tablets can be adjusted by
lowering the lower punch using the capacity regulating screw.
Lowering the punch to a preset point leads to higher powder
filling volume and more tablet weight.
The tablet weight also depends on the granulation or powder
density; the higher the density the higher the weight at the same
depth.

17
 16/04/2020

Single punch tablet press - operation

Filling stage:
At this stage, the hopper shoe moves forward to be right above
the die allowing for die filling.
At the same time, the lower punch is lowered to the preset point
to form a cavity in the die to provide a volume corresponding to
the correct fill weight for the tablet. While the upper punch is in
the raised position.

Single punch tablet press - operation

Compression stage:
After filling, the
, hopper shoe moves aside away from the die
cavity.

The lower punch remains stationary, while the upper punch

comes down to the die to compress the powders/granules into a
tablet.

18
 16/04/2020

Single punch tablet press - operation

Ejection stage:
After compression, the upper punch moves upward and
simultaneously the lower punch moves upward to eject tablet
out of die.
At this time the shoe comes back over the die thus pushing the
ejected tablet into a collector.
Now the lower punch is lowered for another filling and the three
stages are repeated.

Multi-station or rotary tablet press

Main Parts
 In this type, there are a number of dies and sets of punches (up to 60 or
more)
 Dies are hold in a rotating table, called die table.

19
 16/04/2020

Multi-station or rotary tablet press

Main Parts
Both die table and punches rotate
together so that one die is always
associated with one pair of punches
Upon rotation: filling, compression and
ejection happen simultaneously.
The vertical movement of the punches is
controlled by fixed cam tracks

Multi-station or rotary tablet press

20
 16/04/2020

Multi-station or rotary tablet press

1. Filling
 From the hopper the powder flow by gravity into the
die table.
 The powder is fed into the die by feed frame.

 For filling to happen, lower punches is lower to the

lowest position by the cam track (L2-L7). This allows dies
to overfill with powder.
 Before lower punches leave the feed frame, they rise feed frame
slightly to expel excess granules giving the desired
amount for tablet weight (L8).
 Weight of tablets can be controlled by capacity
adjuster which allows for lowering or rising the position
of this cam; lowering cam leads to more tablet weight capacity
and vice-versa. adjuster

Multi-station or rotary tablet press

2. Compression: Upper
compression
 After die filling, lower punches leave the feed frame roll
and travel over cam (above lower compression
roll). Thus, the lower punch is raised into the die (L9-
L13).
 Simultaneously, the upper punches ride beneath
the upper compression roll. These will cause the
upper punch to enter into the die to certain
distance (U9-U13).
Lower
 The powder or granulation inside die will be compression
squeezed and compacted. roll

21
 16/04/2020

Multi-station or rotary tablet press

3. Ejection
 After compression, the upper punches are
withdrawn from the dies as they follow the upper
cam (U14-U16).
 At the same time the lower punches ride up the
cam to bring the tablet slightly above the surface of
the die (L14-L16).

 The tablet hit a “sweep off blade” attached to the

front of the feeding frame and slide down into a
collecting drum.

22