Tablet Compression operation

Part 6

Industrial pharmacy

5th class

1st semester
Tablet Compression Machines
Tablets are made by compressing a formulation
containing a drug or drugs with excipients on
stamping machines called presses.

 Tablet compression machines or tablet presses

are designed with the following basic
components:
1. Hopper(s) for holding and feeding granulation to be
compressed.
2. Dies that define the size and shape of the tablet.
3. Punches for compressing the granulation within the dies.
4. Cam tracks for guiding the movement of the punches.
5. A feeding mechanism for moving granulation from the
hopper into the dies.
Tablet presses are classified
as either single punch or
multi-station rotary
presses:
1. All of the compression is
applied by the upper
punch, making the single
punch machine a "stamping
press“.
2. Multi-station presses are
termed rotary because the
head of the tablet machine
that holds the upper
punches, dies, and lower
punches in place rotates.
Note:
i. As the head rotates, the punches are guided up and
down by fixed cam tracks (control the sequence of
filling, compression, and ejection).

ii. The portions of the head that hold the upper and
lower punches are called the upper and lower
turrets respectively.

iii. The portion holding the dies is called the die table.
Compression cycle
A. Granulation stored in a hopper that empties into the
feed-frame which has several interconnected
compartments.
B. These compartments spread the granulation over a
wide area to provide time for the dies to fill.
C. The pull-down cam guides the lower punches to the
bottom of their vertical travel, allowing the dies to
overfill.
D. The punches then pass over a weight control cam,
which reduces the fill in the dies to the desired
amount.
E. A wipe-off blade 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.
F. Next, the lower punches travel over the lower
compression roll.
G. while simultaneously the
upper punches ride beneath
the upper compression roll.
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.
H. To regulate the upward
movement of the lower
punches, the height of the
lower pressure roll is
changed.
I. After the moment of
compression, the upper
punches are withdrawn as
they follow the upper punch
raising cam.
G. The lower punches ride up the cam, which brings the
tablets flush with or slightly above the surface of the
dies. The exact position is determined by a threaded
bolt called the ejector knob.
H. 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 pulldown cam (C), and the cycle is repeated.

Note:
Such features as capacity, speed, maximum weight,
and pressure vary with the design of the equipment, but
the basic elements remain essentially the same.

A tablet machine's output is regulated by three

basic characteristics of its design:
1. Number of tooling sets (dies, upper and lower punches)
2. Number of compression stations
3. Rotational speed of the press
Notes:
I. In general, all rotary presses are engineered for fast and
economical production of all kinds of tablets. (Larger machines can
readily produce several million tablets each in a working day, and their
performance can be geared to continuous low-maintenance operation).

II. Many modifications and options can be obtained from various

manufacturers.
(One modification, which is found on most modern high-speed tablet presses, use
of hydraulic or pneumatic pressure to control the pressure rolls in
place of the older spring type pressure).

 A smoother pressure or compressive load force over a longer period of

time.
 More accurate and can be set with closer tolerances, which do not
change with time or fatigue.
 Compression Machine Tooling
The size and
shape of a The tooling must meet many
tablet as well requirements:
as certain
identification
markings are 1. Satisfy the needs of dosage
determined uniformity
by
compression
machine 2. Production efficiency
tooling set.

3. Esthetic appearance.
Tooling sets
 BB tooling (5.25 inches in length,
nominal barrel diameter of 0.75
inches and 1-inch head diameter).
 B tooling (identical to the BB type
except that the lower punch is only
3 ⁄ inches long).
 D tooling is popular for large tablets,
(1-inch barrel diameter, 1 ⁄ -inch
head diameter, and 5.25-inch
length).

 The dies that are used with the

above punches are either:
a) 0.945-inch outside diameter
(OD) die capable of making a
⁄ -inch round tablet or ⁄ -
inch capsule-shaped tablet.
b) 1 ⁄ -inch OD die capable of
handling a ⁄ -inch round or
⁄ -inch capsule shaped tablet.
 Important notes:
I. Several types of steel are normally used in the
manufacture of compression tooling that differ in:
(toughness to withstand the cyclic compacting forces,
ductility (elasticity), and in wear resistance).
II. No single steel type has a high resistance to abrasive wear
and a high ductility.

III. Selection of the best steel for a specific application

must be based on:
a. Experience and an accumulated history of the product
being tabletted
b. Selection of the proper steel for a specific use
c. Shape of the punch tip, whether or not debossing is to
be employed on the tooling
d. The expected compression forces
e. Materials to be processed are abrasive or corrosive.
IV. Tooling can be made with certain information
(aid in producing a visibly unique tablet
product).
Ex: Company names or symbols, trade names,
dosage strength, or National Drug Code (NDC)
numbers can be cut or engraved into a punch face,
or the punches may be scored, to produce uniquely
embossed or engraved tablets.

V. Even though tooling design would appear to

be limitless, certain practical aspects do limit
design implementation.

Because of the movement of tooling during a

compression operation, certain tablet shapes or
contour configurations perform better than others.
Ex1: Round tablets perform better than irregularly shaped tooling
since they do not require "keying" to maintain the proper upper
punch orientation with the die.

Ex2: When the tip on an upper punch is not round, it must

not rotate, or it will strike the edge of the die hole as it for
compression. (To prevent this, a slot is cut longitudinally
into the barrel of the punch and a key is inserted).

key protrudes a short distance so that it engages a similar

slot cut into the upper punch guides on the tablet press.

VI. Lower punches do not need keys (because their

tips remain within the die bore, which controls the
axial movement of the punch).
VII. Because keyed punches cannot rotate, wear is
distributed unevenly, and punch life is shortened.
How to put tools?
When a press is set up with keyed punches, the
upper punches are inserted first to determine the
placement of the dies.
Once the dies are properly aligned and seated,
they are locked in place, and the lower punches are
inserted.

Notes:
i. The more curvature that is built into a tablet
contour, the more difficult it is to compress,
especially if the tablet tends to laminate or cap.
ii. The engraving or embossing on a tablet must be
designed to be legible, must not add to
compression problems, must fit on the tablet
surface.
 Tools problems:
Because of its hard steel structure, tablet tooling may appear
to be indestructible.
a. During normal use, the punches and dies
become worn, and the cyclic application of
stress can cause the steel to fatigue and break.
b. Improper storage and handling can readily
result in damage that necessitates discarding of
an entire tooling set.
c. The punch tips are especially delicate and
susceptible to damage if the tips make contact
with each other, the dies, or the press turret
upon insertion or removal of the tools from the
tablet machine.
Solving tool problems
 To avoid tooling damage,
compressive loads or pressures at
the pressure rolls must be
translated into a calculation of
pressure at the punch tips.

 As tablet punch diameter

decreases, less force is required to
produce the same pressure at the
punch face, since the face
represents a smaller fraction of a
unit area (square inch).
 Auxiliary Equipment
Problem 1: the speed of the die table is such that the
dwell time of a die under the feed frame is too short to
allow for adequate or consistent gravity filling of the die
with granulation.

Causes: Improper filling of the dies with granulation

results in unsatisfactory weight variation and content
uniformity of the resulting tablets. A similar result can
occur with a poorly flowing granulation.

Solution: mechanized feeders can be employed to force

granulation into the dies
Problem 2: The high tablet output rates of modem presses
demand that the granulation hoppers be refilled at frequent
intervals; the larger the tablet is, the more frequently the
hopper needs to be replenished.
Causes: Allowing a tablet machine to run "dry" results in a
series of rapidly degenerating and unacceptable events:
1- low-weight tablets and tablets with poor weight variation
are produced.
2- soft granulation is unable to be formed into tablets.
3- tooling is usually ruined, particularly with thin tablets, by
the punches being forced together without any granulation
between them. Because of the relatively low volume of press
hoppers, the filling of hoppers by hand on high-speed presses
is inefficient, increases the risk of-punch damage, and can
contribute to weight variation problems.
Solution: mechanized equipment has been developed to
load granulation into the press hoppers.
Problem 3: handling large quantities of material into the
hoppers.

Solution: place bulk granulation containers directly above

tabletting machines to gravity-feed the granulation into
hoppers.
1. Either by placing bulk granulation containers on floors
above a tablet machine, and granulation can then be
directed through openings in the floor into the hoppers.
2. Or granulation containers can be held on mezzanines
above tablet machines. If such overhead room is
unavailable, hoists and mechanical lifts can be used to
elevate granulation containers or material transfer
devices directly in position above the press.
3. Also granulation level sensors can be used to stop the press
automatically when the granulation level drops to a
critical level in the hopper.
Problem 4: The high rate of tablet output with modem presses calls
for a higher frequency or even continuous monitoring of tablet
weight.
Solution: Electronic monitoring devices, such as the Thomas Tablet
Sentinel, Phannakontroll, and the Kilian Control System-Me:
1. Monitor the force at each compression station, which correlates
with tablet weight.
2. Monitors are also capable of initiating corrective actions, altering
the amount of die fill to maintain a fixed force, ejecting tablets
that are out of specification, counting, and documenting the
machine operation throughout the run.

Another auxiliary: In almost all cases, tablets coming off a tablet

machine bear excess powder and are run through a tablet deduster to
remove that excess.
In Process Quality
control

Part 7
Industrial pharmacy

5th class

1st semester
 In-Process Quality Control
• During the compression of tablets, in-process
tests are routinely run to monitor the process,
including tests:

• The in-process tests are performed by

production and/or quality control (QC)
 Processing Problems
The source of the problem:
1. Formulation
2. Compression equipment
3. Combination of the two.

Capping and Lamination.

Capping: describe the partial or complete separation of the top or
bottom crowns of a tablet from the main body of the tablet.
Lamination: is the separation of a tablet into two or more-distinct
layers.
Appear immediately after compression or occur hours or even
days, later.

Detection of these problems: subjecting tablets to friability test.

 Causes of the problems:
1. During the compression process, air is entrapped among
the particles or granules and does not escape until the
compression pressure is released.
2. Capping and lamination are due to the deformational
properties of the formulation during and immediately
following compression.
Mechansim:
I. During compaction, particles undergo sufficient plastic
deformation to produce die-wall pressures greater than
can be relieved by elastic recovery when the punch
pressure is removed.
II. In some materials, this die-wall pressure causes enough
internal stress to cause a crack to propagate and initiate
fracture of the compact in the die.
III. Ifthe excess stresses do not initiate fracture upon
decompression in the die, the compact may laminate or
cap upon ejection from the die.
IV.The emerging portion of the compact expands while
the confined portion cannot, thus concentrating shear
stresses at the edge of the die and causing a break to
develop.

Rapid decompression results in tablets that fracture.

While tablets that do not fracture have the ability to

relieve shear stress (stress relaxation) which is time-
dependent; therefore, the occurrence of tablet fracture is
also time dependent.
Elimination of capping and
lamination:
1. Precompression
2. Slowing the tabletting rate
3. Reducing the final compression pressure.

I. As the stress relaxation time is increased

II. The amount of stress needing to be
relieved is reduced
III. Allowing an intact compact to be formed.

Problem: deep concave punches

produce tablets that cap (curved part of
such tablets expands radially while the body of
the tablet cannot, which establishes a shear
stress that produces the fracture).
Solution: Flat punches may eliminate this
additional shear stress.
Problem: A granulation that is too dry tends to
cap or laminate for lack of cohesion.
Solution: A certain percentage of moisture is often
essential for good compaction (in moisture-critical
granulations, the addition of a hygroscopic substance,
e.g., sorbitol, methylcellulose, or PEG 4000, can help to
maintain a proper moisture level).

Problem: Capping and lamination in direct

compression product (powder or fine particulate
materials may not be compressible or may have poor
compression properties).
Solution: Relative compressibility of various materials
may be reflected by their degree of consolidation
(crown thickness) when compressed in standard tooling
under identical compression conditions.
Problem: Tablet tooling is a cause of capping.

Causes:
1. The concave or beveled edge faces of punches
(gradually curve inward with use and form a "claw"
that can pull off the crowns of a tablet).
2. Wear in the upper punch (accelerates this claw
formation by permitting the punch tips to strike the
edges of the die hole).
3. The greater the radius of curvature of the punch
face (greater is the force exerted on the edges and
the less on the center of the tablet at the moment
of compression).
Problem: Dies develop a wear "ring" in the area of
compression.

As the ring develops, and enlarges, the tablets that are

compressed in the rings have a diameter that is too large to pass
easily through the narrower portion of the die above the ring.

Upon ejection, this constriction causes the tablet to cap or

laminate.

Cause:
Wear on tablet tooling increases as the hardness of the
material being compressed increases (most organic
materials are soft; certain inorganic materials such as
magnesium trisilicate are relatively hard and abrasive).
Solution:
1. Turn the die over so that compression occurs in an
unworn area above the ring.
2. On some presses, the depth of penetration of the upper
punch can be regulated so that compression may be
performed over some range of locations within the die.
3. Using dies with tungsten carbide inserts. The carbide is so
durable that the casing wears out before the insert
does.
Problem: The punch remains below the face of the die, so sweep-
off blade cuts off the tablet, leaving the bottom in the die) and can
also result in tablet fracture.

Causes:
1. Incorrect setup of the press causes a capping (the edge of
the tablet catches on the die and chip).
2. The blade is adjusted too high (tablets can start to travel
under it, become stuck, and break off).

The resulting broken pieces of tablets then enter the feed

frame; if they are large enough, they can cause a disruption of
the granulation feed, as well as affect the weight and hardness
of subsequent tablets.

Solution:
Adjust a compressed tablet ejection from the die so the lower punch
must rise flush with or protrude slightly above the face of the die at
the point where the tablet strikes the sweep-off blade.
 Picking and Sticking.
"Picking“: is a term used to describe the
surface material from a tablet that is
sticking to and being removed from the
tablet's surface by a punch.

Causes: concern when punch tips have

engraving or embossing.
Example: Small enclosed areas such as those
found in the letters "B," "A," and "0" are difficult
to manufacture cleanly.

Tablet materials that stick to the punches can

accumulate to the point of obliterating the tip
design.
Sticking: refers to tablet material adhering to the die wall.

Additional force is required to overcome the friction between the tablet and
the die wall during ejection.

Serious sticking at ejection can cause chipping of a tablet’s edges and can
produce a rough edge.

Also, a sticking problem does not allow the lower punch free movement and
therefore can place unusual stress on the cam tracks and punch heads, resulting
in their damage.

Sticking can also apply to the buildup of material on punch faces.

Solution:
1. Lettering should be designed as large as possible,
particularly on punches with small diameters. The
tablet can perhaps be reformulated to a larger size.
2. Plating of the punch faces with chromium (produce a
smooth, nonadherent face).
3. Colloidal silica added to the formula (acts as a
polishing agent and makes the punch faces smooth so
that material does not cling to them). Frictional nature
of this material may require additional lubrication to
facilitate release of the tablet from the die.
4. Additional binder or a change in binder (make granules
more cohesive, less adherent than before).
Problem: low-melting-point substances, either active
ingredients or additives such as stearic acid and polyethylene
glycol, may soften sufficiently from the heat of compression to
cause sticking.

Solution:
1. Dilution of the active ingredient with additional higher-
melting-point materials consequent increase in the size
of the tablet that may help.
2. The level of low-melting-point lubricants may be reduced, or
higher-melting-point replacements may be substituted.
3. When a low-melting-point medicament is present in high
concentration, refrigeration of the granulation and the press
may be in order.
4. Excessive moisture may be responsible for sticking, and
further drying of the granulation is then required.
Mottling is an unequal distribution of color on a
tablet, with light or dark areas standing out in an
otherwise uniform surface.
Mottling.
Cause of mottling: is a drug whose color differs
from the tablet excipients or a drug whose
degradation products are colored.

Solution: use of colorants may solve the above

problem but can create others.
• A dye can cause mottling by migrating to the
surface of a granulation during drying.
• To overcome this difficulty, the formulator may
(change the solvent system, change the
binder system, reduce the drying
temperature, or grind to a smaller particle
size).
Note: The use of colorants in direct compression
formulations can lead to mottling if the dye is not well
dispersed or if its particle size is too large.
Problem: Certain colored adhesive gel solutions may not be
distributed well because they must be hot when added to
much cooler powder mixtures. The adhesive then precipitates
from solution and carries most of the color with it.

Temporary solution: Further wetting, even overwetting,

is needed to disperse the binder and the color. The
additional mixing and increased activation of the binder,
however, may result in tablets with increased disintegration
times.

Permeant solution: Therefore, a better practice may be to:

1- incorporate fine powder adhesives such as acacia and
tragacanth into the product before adding the granulating
fluid,
2- or disperse a dry color additive during the powder blending
step.
 Weight Variation.

The weight of a tablet being compressed is determined by

the amount of granulation in the die prior to compression.

Anything that can alter the die-filling process can alter

tablet weight and weight variation.
 Granule Size and Size Distribution
Before Compression.
Variations in the ratio of small to large granules and in the
magnitude of difference between granule sizes

Influence how the void spaces between particles are filled.

• If large granules are used to fill a small die cavity (relatively

few granules are required) the average may represent
a high percentage weight variation.
• If hundreds of granules are required on the average for die fill,
(variation of a few granules around the average would
produce a minor weight variation, given a narrow particle size
range).
 Poor Flow.
The die-fill process is based on a continuous and uniform flow of
granulation from the hopper through the feed frame.

Problem:
a. When the granulation does not flow readily, it tends to move
spasmodically through the feed frame so that some dies are
incompletely filled.
b. Similarly, dies are not filled properly when machine speed is in
excess of the granulation's flow capabilities.

Solution:
1. Addition of a glidant (talcum or colloidal silica), or an increase in the
amount already present, may be helpful.
2. Induced die feeders, which mechanically "force" the granulation
down into the die cavities as they pass beneath the feed frame.
Problem: Poor flow through the feed frame (a sign that the granulation is
not flowing properly out of the hopper).

As particulate solids move under the force of gravity through progressively

smaller openings; they are subjected to uneven pressures from the mass
above and alongside.

Depending on the geometry of the hopper, this situation may give rise to
one or another of two causes for poor flow: "arching" or "bridging,“ and "rat-
holing.

When poor hopper flow occurs, it may be controllable with vibrators

attached to the hopper sides to induce the granulation flow.
Another problem arise: most tablet granulations consist of
materials with a range of particle sizes.

Vibration or mixing action of the flow promoting devices may

induce segregation and stratification of the particles.

The larger particles tend to drift upward while the smaller

particles sift downward.

Changes in tablet weight and weight variation but it can also

lead to poor content uniformity, since drug is often not uniformly
distributed between the larger and smaller particles.

A new feed frame design that accommodated excessive flow

from the hopper without compromising uniform weight
variation.
 Poor Mixing.
Problem 1: lubricants and glidants are not thoroughly
distributed.
The flow of particles is then impaired, and the granules
do not move efficiently into the dies.

Problem 2: a tendency to minimize the mixing time

during lubricant addition to prevent or reduce granule
friability
Inadequate mixing during this stage can result in
unsatisfactory granulation flow.
 Punch Variation.

Problem: When lower punches are of unequal lengths-

the difference may be only a few thousandths of an inch-
the fill in each die varies because the fill is volumetric.

Solution: Only a good punch and die control program can

provide tooling of uniform dimensions.
 Hardness Variation.
Hardness variation weight variation.

Hardness depends on:

1. Weight of material
2. Space between the upper and lower punches at the
moment of compression.

If the volume of material or the distance between

punches varies hardness is inconsistent.
 Double Impression.
This involves only punches that have a monogram or
other engraving on them.

Problem: At the moment of compression, the tablet receives

the imprint of the punch. On some machines, the lower punch is
free to drop and then travel uncontrolled for a short distance
before it rides up the ejection cam to push the tablet out of the
die.

During its free travel, it rotates.

At this point, the punch may make a new, although lighter,

impression on the bottom of the tablet, resulting in a double
imprint.
Problem: Similar problems can be encountered with
engraved upper punches and tablet machines that utilize two
compression stages to compress a tablet.

The first stage (precompression) uses a lower compaction force

than the final compression stage

But the tablet does receive the imprint of the punch.

If the upper punch is uncontrolled, it can rotate during the short

travel to the final compression stage and thus create a double
imprint.

Solution for both problems: The newer presses have

anti-turning devices as an integral part of their design and
construction.