Description
In the normal process of developing formulations,
and in the routine manufacture of tablets, various
defects are observed. Sometimes, the source of the
problem or the defect is the formulation, the
compression equipment, or a combination of the
two.
Some defects are noticed immediately during
manufacturing but others may be noticed during
storage as in the case of capping.
CAPPING AND LAMINATION
Capping is defined as 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.
These processing problems are readily apparent immediately
after compression or may occur hours or even days later.
Subjecting tablets to the friability test is the quickest way of
revealing such problems.
CAPPING AND LAMINATION
Causes
Air entrapment . Due to the air–entrapment in a compact
during compression, and subsequent expansion of tablet on
ejection of a tablet from a die.
capping and lamination may also be encountered in direct
compression
Tablet tooling (punch worn tips, deep concave punch) can
cause capping .
Incorrect setup at the press.
CORRECTIVE ACTIONS ( Formulation)
Sr. CAUSES REMEDIES
No.
1. Large amount of fines in the Remove some or all fines through 100 to 200 mesh screen
granulation
2. Too dry or very low moisture content Moisten the granules suitably. Add hygroscopic substance
(leading to loss of proper binding e.g.: Sorbitol, Methylcellulose or PEG-4000.
action).
3. Not thoroughly dried granules. Dry the granules properly.
4. Insufficient amount of binder or Increasing the amount of binder OR
improper binder.
Adding dry binder such as pre-gelatinized Starch, Gum
acacia, powdered Sorbitol, PVP, hydrophilic Silica or
powdered Sugar.
5. Insufficient or improper lubricant. Increase the amount of lubricant or change the type of
lubricant.
6. Granular mass too cold to compress Compress at room temperature.
firm.
Machine
Chipping : is breaking of the edge of tablet during
compression.
Reason:
Incorrect machine settings.
The Causes and Remedies of Chipping related to
‘Formulation’
CAUSES REMEDIES
Sr.
No.
1. Sticking on punch faces Dry the granules properly or increase lubrication.
2. Too dry granules. Moisten the granules to plasticize. Add
hygroscopic substances.
3. Too much binding causes chipping Optimize binding, or use dry binders.
at bottom.
Cracking: small, fine cracks observed in the upper and
lower central surface of tablets or very rarely on the
side wall are referred to as cracks .
Reason:
It is observed as a result of rapid expansion of tablets,
especially when deep concave punches are used.
The Causes and Remedies of Cracking related to
‘Formulation’
CAUSES REMEDIES
Sr. No.
1. Large size of granules. Reduce granule size. Add fines.
2. Too dry granules. Moisten the granules properly and add proper amount of
binder.
3. Tablets expand. Improve granulation. Add dry binders.
4. Granulation too cold. Compress at room temperature.
– Capping is prevented by using ——- face
punches
(a) Flat (b) concave
(c) convex (d) worn
PICKING AND STICKING
Picking refers to term used when small
amount of surface material of tablet
stick to and being removed off from the
tablets surface by a punch face.
It is of particular concern when punch
tips have engraving or embossing.
Small enclosed letter (A,B,O,Q) are
difficult to manufacturing cleanly
Tablet materials adhering to punches can
accumulate to the point of obliterating
the tip design.
Sticking refers to a tablet material
adhering to the die wall.
It results in the buildup of material on
punch faces.
• Low melting point substances, either active ingredients or
additives such as stearic acid or PEG, may soften sufficiently
from the heat of compression.
• Excessive moisture may be responsible for sticking and further
drying of granulation is then required.
Remedy
• Lettering should be designed as large as possible particularly on
punches with small diameter.
• The tablets can perhaps be reformulated to larger size.
• Plating punch face with chromium is a method of producing a
smooth , non adherent face.
• Colloidal silica added to the formula act as a polishing agent
and makes the punch faces too smooth so that material does not
sticking to them.
• Lubricants required to overcome friction between tablet and die
wall during ejection.
BINDING
Binding in the die is the term used when tablet stick to the
die and does not eject properly.
Tablets adhere, seize and tear in the die. A film is formed
in the die and tablet ejection is hindered and become
difficult and accompanied by characteristic noise.
The edge of tablet becomes rough , tablet side cracks and it
may be crumble.
Causes :
Poor lubrication of granules
Under dried granules
Dirty or worn out dies
Fine powder from granules seep outward and forms
thick layer on die which hinders free movement of
punches
MOTTLING
Mottling is unequal distribution of color on a tablet, with light or dark areas
standing out in an otherwise uniform surface.
Causes and corrective actions:
Drug whose color differs from the tablet excipients or a drug whose degradation
products are colored.
Use of colorants
Migration of dyes to the surface of granulation during drying
Change the solvent system (binding system)
Reduce the drying temperature
Insoluble lake
The use of colorant in direct compression formulations can lead to mottling if
dye is not well dispersed or if its size too large
Mix properly and reduce size to
a small particle size if too large
– Match the following and find out the correct combination
1. Capping (A) Separation of a tablet into 2 or more layers
2. Lamination (B) Unequal distribution of color on a tablet
3. Mottling (C) Separation of top/bottom crowns of a tablet
from the main body
4. Sticking (D) Adherence of tablet material to the die wall
DOUBLE IMPRESSION
This problem is encountered with punches that have a
monogram or other engraving on them.
If the letters of tablet are impressed twice then they
are known as double impression
Double impression
WEIGHT VARIATION
Weight of tablet determined by amount of granulation in die prior to
compression. Therefore, anything that alter die-filling alter tablet
weight.
Causes and remedies
Granular size and size distribution before compression:
Variation in the ratio of small and large granules influence how the void
spaces between particles are filled. Thus may change the weight of fill in
each die.
Poor flow through the Feed frame
As particle move under the force of gravity through progressively smaller
openings, they are subjected to uneven pressures from mass above and
alongside. Depending on geometry of the hopper, this situation may give
rise to one or another of two cause for poor flow ( arching) or (bridging of
particles that blocks flow) and (rat-holing) (an empty tunnel over the
orifice due to core-flow).
Particles size should be optimum for good flowing of granules from
hopper to die.
Poor mixing
Sometimes lubricants and glidants are not properly distributed. Then
the flow of particles impaired and granules do not move efficiently
into die.
• Good lubricant should be used. Uniform mixing of the materials
can overcome this defect
• Lubricant & glidants should be added in mixing time.
Punch variation
When lower punches of unequal lengths. The difference may be only a
few thousandth of an inch. The fill in each die varies because the fill is
volumetric.
• Good punch and die which has uniform dimensions can control
weight variation.
Machines built to compress tablets consist of:
1- Hopper: for holding granulations for compressing.
2- Feed frame: for distributing the materials into the
dies.
3- Dies: for controlling the size and the shape of the
tablet.
4- Punches: for compressing the granulations within
the dies.
HARDNESS VARIATION
Hardness variation is a problem that has the same
causes as weight variation.
Tablet which is very hard is not acceptable as well as
very soft because this type of tablet would be broken
rapidly or slowly but not in consideration time.
Causes and remedies
Hardness depend on weight of material weight
should be taken carefully.
The space between upper & lower punches at moment
of compression . If the volume of material or distance
between punches varies leading to in consist hardness.
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