Problems Of Tablet Manufacturing

Contents
Introduction Problems and remedies for tablet coating
Capping Blistering
Lamination / Laminating Chipping
Chipping Cratering
Cracking Picking
Sticking / Filming Pitting
Picking Blooming
Binding Blushing
Mottling Colour variation
Double impression Infilling
Orange peel/Roughness
Cracking/Splitting

Introduction

An ideal tablet should be free from any visual defect or functional defect.
In manufacturing technology a lot of advancement happened in last 50 years, in techno, in the process
and in the materials being used but problems has not been decreased.
Demands of Quality have increased in one hand on the other hand the process is a complex one.
Manufacturing pharmacist often encounters number of problems during manufacturing. Majority of visual
defects are due to inadequate fines or inadequate moisture in the granules ready for compression or due
to faulty machine setting. Functional defects are due to faulty formulation.
Knowledge of granulation processing and tablet presses may help solving the problems

The Imperfections:

The imperfections or ‘VISUAL DEFECTS’ may happen for the following factors-
1. Tableting Process
2. Excipient
3. Machine
Process Related Defects
i) CAPPING : It is due air-entrapment in the granular material.
ii) LAMINATION : It is due air-entrapment in the granular material.
iii) CRACKING : It is due to rapid expansion of tablets when deep concave punches are used.
Excipient Related Defects
iv) CHIPPING: It is due to very dry granules
v) STICKING
vi) PICKING
vii) BINDING
viii) MOTTLING - more than one factor-Due to a coloured drug, which has different colour than the rest
of the granular material? (Excipient- related); improper mixing of granular material (Process-related); dirt
in the granular material or on punch faces; oil spots by using oily lubricant.
Machine Related Defect
ix) DOUBLE IMPRESSION - due to free rotation of the punches.
Causes and Remedies

Capping
• ‘Capping’ is the term used, when the upper or lower segment of the tablet separates
horizontally, either partially or completely from the main body of a tablet and comes off as a cap,
during ejection from the tablet press, or during subsequent handling.
• Reason : Capping is usually due to the air–entrapment in a compact during compression, and
subsequent expansion of tablet on ejection of a tablet from a die.

CAUSES AND REMEDIES OF CAPPING RELATED TO ‘FORMULATION

CAUSES
Large amount of fines in the granulation
Too dry or very low moisture content (leading to loss
of proper binding action).
Not thoroughly dried granules.
Insufficient amount of binder or improper binder.
Insufficient or improper lubricant.
Granular mass too cold to compress firm.
REMEDIES
Remove some or all fines through 100 to 200 mesh
screen
Moisten the granules suitably. Add hygroscopic
substance e.g.: sorbitol, methyl- cellulose or PEG-
4000.
Dry the granules properly.
Increasing the mount of binder OR Adding dry binder
such as pre-gelatinized starch, gum acacia, powdered
sorbitol, PVP, hydrophilic silica or powdered sugar.
Increase the amount of lubricant or change the type of
lubricant.
Compress at room temperature.

CAPPING RELATED TO ‘MACHINE’-DIES, PUNCHES AND TABLET PRESS

CAUSES REMEDIES
Polish dies properly. Investigate other steels or other
Poorly finished dies.
materials.
Deep concave punches or beveled-edge faces of
Use flat punches.
punches.
Lower punch remains below the face of die during
Make proper setting of lower punch during ejection.
ejection.
Adjust sweep-off blade correctly to facilitate proper
Incorrect adjustment of sweep-off blade.
ejection.
High turret speed. Reduce speed of turret (Increase dwell time).

Lamination / Laminating

Definition: ‘Lamination’ is the separation of a tablet into two or more distinct horizontal layers.
Reason: Air–entrapment during compression and subsequent release on ejection.
The condition is exaggerated by higher speed of turret.

CAUSES AND REMEDIES OF LAMINATION RELATED TO FORMULATION (GRANULATION) and

Lamination related to MACHINE (Dies, Punches and Tablet Press)
CAUSES REMEDIES
Oily or waxy materials in granules Modify mixing process. Add adsorbent or absorbent.
Too much of hydrophobic lubricant Use a less amount of lubricant or change the type of
e.g.: Magnesium-stearate. lubricant.
Rapid relaxation of the peripheral regions of a tablet, Use tapered dies, i.e. upper part of the die bore has
on ejection from a die. an outward taper of 3° to 5°.
Rapid decompression Use pre-compression step. Reduce turret speed and
reduce the final compression pressure.
Chipping
Definition: ‘Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press or
during subsequent handling and coating operations.
Reason: Incorrect machine settings, specially mis-set ejection take-off.

CAUSES AND REMEDIES OF CHIPPING RELATED TO FORMULATION (GRANULATION) ARE AS FOLLOWS

CAUSES REMEDIES
Sticking on punch faces Dry the granules properly or increase lubrication.
Too dry granules. Moisten the granules to plasticize. Add hygroscopic
substances.
Too much binding causes chipping at bottom. Optimize binding, or use dry binders.

CAUSES AND REMEDIES OF CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES
Groove of die worn at compression point.
Barreled die (center of the die wider than ends)
Edge of punch face turned inside/inward.
Concavity too deep to compress properly.
Groove of die worn at compression point.
Barreled die (center of the die wider than ends)
Edge of punch face turned inside/inward.
Concavity too deep to compress properly.
REMEDIES
Polish to open end, reverse or replace the die.
Polish the die to make it cylindrical
Polish the punch edges
Reduce concavity of punch faces. Use flat punches.
Polish to open end, reverse or replace the die.
Polish the die to make it cylindrical
Polish the punch edges
Reduce concavity of punch faces. Use flat punches.

Cracking
Definition: Small, fine cracks observed on the upper and lower central surface of tablets, or very rarely on
the sidewall are referred to as ‘Cracks’.
Reason: It is observed as a result of rapid expansion of tablets, especially when deep concave punches
are used.
CAUSES AND REMEDIES OF CRACKING RELATED TO FORMULATION (GRANULATION)
CAUSES REMEDIES
Large size of granules Reduce granule size. Add fines.
Moisten the granules properly and add proper amount of
Too dry granules.
binder.
Tablets expand. Improve granulation. Add dry binders.
Granulation too cold. Compress at room temperature.
CAUSES AND REMEDIES OF CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Tablet expands on ejection due to air entrapment. Use tapered die.
Deep concavities cause cracking while Use special take-off.
removing tablets
Tablet expands on ejection due to air entrapment. Use tapered die.
Deep concavities cause cracking while Use special take-off.
removing tablets

Sticking/Filming
Definition: ‘Sticking’ refers to the tablet material adhering to the die wall.
• Filming is a slow form of sticking and is largely due to excess moisture in the granulation.
Reason: Improperly dried or improperly lubricated granules.
CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION)
CAUSES REMEDIES
Granules not dried properly. Dry the granules properly. Make moisture analysis to determine
limits.
Too little or improper lubrication. Increase or change lubricant .
Too much binder Reduce the amount of binder or use a different type of binder.
Hygroscopic granular material. Modify granulation and compress under controlled humidity.
Oily or way materials Modify mixing process. Add an absorbent.
Too soft or weak granules. Optimize the amount of binder and granulation technique.

CAUSES AND REMEDIES OF STICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Concavity too deep for granulation. Reduce concavity to optimum.
Too little pressure. Increase pressure.
Compressing too fast. Reduce speed.

Picking
Definition: ‘Picking’ is the term used when a small amount of material from a tablet is sticking to
and being removed off from the tablet-surface by a punch face.
• The problem is more prevalent on the upper punch faces than on the lower ones. The
problem worsens, if tablets are repeatedly manufactured in this station of tooling because of the
more and more material getting added to the already stuck material on the punch face.
Reason: Picking is of particular concern when punch tips have engraving or embossing letters, as
well as the granular material is improperly dried.

CAUSES AND REMEDIES OF PICKING RELATED TO FORMULATION (GRANULATION)

CAUSES
Excessive moisture in granules.
Too little or improper lubrication.
Low melting point substances, may soften from the
heat of compression and lead to picking.
Low melting point medicament in high concentration.
Too warm granules when compressing.
Too much amount of binder.
REMEDIES
Dry properly the granules, determine optimum limit.
Increase lubrication; use colloidal silica as a ‘polishing
agent’, so that material does not cling to punch faces.
Add high melting-point materials. Use high meting point
lubricants.
Refrigerate granules and the entire tablet press.
Compress at room temperature. Cool sufficiently before
compression.
Reduce the amount of binder, change the type or use
dry binders.

CAUSES AND REMEDIES OF PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Rough or scratched punch faces. Polish faces to high luster.
Embossing or engraving letters on punch faces such as Design lettering as large as possible.
B, A, O, R, P, Q, G. Plate the punch faces with chromium to produce a
smooth and non-adherent face.
Bevels or dividing lines too deep. Reduce depths and sharpness.
Pressure applied is not enough; too soft tablets. Increase pressure to optimum.

Binding
Definition: ‘Binding’ in the die, is the term used when the tablets adhere, seize or tear in the die. A
film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are
cracked and it may crumble apart.
Reason: Binding is usually due to excessive amount of moisture in granules, lack of lubrication
and/or use of worn dies.
CAUSES AND REMEDIES OF BINDING RELATED TO FORMULATION (GRANULATION)
CAUSES REMEDIES
Too moist granules and extrudes around lower punch. Dry the granules properly.
Insufficient or improper lubricant. Increase the amount of lubricant or use a more effective
lubricant.
Too coarse granules. Reduce granular size, add more fines, and increase the
quantity of lubricant.
Too hard granules for the lubricant to be effective. Modify granulation. Reduce granular size.
Granular material very abrasive and cutting into dies. If coarse granules, reduce its size.
Use wear-resistant dies.
Granular material too warm, sticks to the die. Reduce temperature.
Increase clearance if it is extruding.
CAUSES AND REMEDIES OF BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Poorly finished dies Polish the dies properly.
Rough dies due to abrasion, corrosion. Investigate other steels or other materials or modify granulation.
Undersized dies. Too little clearance. Rework to proper size.
Increase clearance.
Too much pressure in the tablet press. Reduce pressure. OR
Modify granulation. HUA-
Mottling
• Definition: ‘Mottling’ is the term used to describe an unequal distribution of colour on a
tablet, with light or dark spots standing out in an otherwise uniform surface.
• Reason: One cause of mottling may be a coloured drug, whose colour differs from the colour
of excipients used for granulation of a tablet.
CAUSES AND REMEDIES OF MOTTLING
CAUSES REMEDIES
A coloured drug used along with colourless or Use appropriate colourants.
white-coloured excipients.
A dye migrates to the surface of granulation while Change the solvent system,
drying. Change the binder, Reduce drying
temperature and Use a
smaller particle size.
Improperly mixed dye, especially during ‘Direct Mix properly and reduce size if it is of a larger size to
Compression’. prevent segregation.
Improper mixing of a coloured binder solution. Incorporate dry colour additive during powder
blending step, and finally add granulating liquid.

Double Impression
Definition: ‘Double Impression’ involves only those punches, which have a monogram or other
engraving on them.
Reason: At the moment of compression, the tablet receives the imprint of the punch, the punch rotates
and at this point, the punch may make a new impression on the bottom of the tablet, resulting in
‘Double Impression’.
CAUSE REMEDIES
Free rotation of either upper punch or lower -Use keying in tooling, i.e. inset a key alongside of the   
punch during ejection of a tablet. punch, so that it fits the punch and prevents punch
rotation.
-Newer presses have anti-turning devices, which prevent
punch rotation.
 PROBLEMS AND REMEDIES FOR TABLET COATING

Blistering
Definition: It is local detachment of film from the substrate forming blister.
Reason: Entrapment of gases in or underneath the film due to overheating either during spraying or at
the end of the coating run.
Chipping
Definition: It is defect where the film becomes chipped and dented, usually at the edges of the tablet.
Reason: Decrease in fluidizing air or speed of rotation of the drum in pan coating.
Cratering
Definition: It is defect of film coating whereby volcanic-like craters appears exposing the tablet
surface.
Reason: The coating solution penetrates the surface of the tablet, often at the crown where the
surface is more porous, causing localized disintegration of the core and disruption of the coating.
Picking
Definition: It is defect where isolated areas of film are pulled away from the surface when the
tablet sticks together and then part.
Reason: Conditions similar to cratering that produces an overly wet tablet bed where adjacent tablets
can stick together and then break apart.
Pitting
Definition: It is defect whereby pits occur in the surface of a tablet core without any visible
disruption of the film coating.
Reason: Temperature of the tablet core is greater than the melting point of the materials used
in the tablet formulation.
Blooming
Definition: It is defect where coating becomes dull immediately or after prolonged storage at high
temperatures.
Reason: It is due to collection on the surface of low molecular weight ingredients included in the
coating formulation. In most circumstances the ingredient will be plasticizer.
Blushing
Definition: It is defect best described as whitish specks or haziness in the film.
Reason: It is thought to be due to precipitated polymer exacerbated by the use of high coating
temperature at or above the thermal gelation temperature of the polymers.
Colour variation
Definition: A defect which involves variation in colour of the film.
Reason: Alteration of the frequency and duration of appearance of tablets in the spray zone or the
size/shape of the spray zone.
Infilling
Definition: It is defect that renders the intagliations indistinctness.
Reason: Inability of foam, formed by air spraying of a polymer solution, to break.
Orange peel/Roughness
Definition: It is surface defect resulting in the film being rough and nonglossy. Appearance is similar
to that of an orange.
Reason: Inadequate spreading of the coating solution before drying.
Cracking/Splitting
Definition: It is defect in which the film either cracks across the crown of the tablet (cracking) or
splits around the edges of the tablet (Splitting)
Reason: Internal stress in the film exceeds tensile strength of the film.
 Key wards
During tablet manufacture, an industrial pharmacist usually encounters many problems. Solving these
problems requires an in-depth knowledge of tablet-formulation as well as machine-operating processes.
Capping and Lamination are the defects arising as a result of air-entrapment in the granular material.
Chipping is a defect related arising due to very dry granules.
Cracking is due to rapid expansion of tablets, when deep concave punches are used.
Sticking, Picking and Binding are the imperfections related to more amount of binder in granules.
Mottling is an imperfection arising due to more than one factor: a coloured drug, dirt in granules or the
use of an oily lubricant.
Double-Impression is related to a machine defect: it is caused by the free rotation of punches that
have some engraving on the punch-faces.

Coating defects
Blistering is related to entrapment of gases in or underneath the film due to overheating either during
spraying or at the end of the coating run. Use of mild drying conditions can solve this problem.
Chipping is related to higher degree of attrition associated with the coating process. Increase in hardness
of the film by increasing the molecular weight grade of polymer can solve this problem.
Cratering is related to penetration of the coating solution into the surface of the tablet, often at the crown
where the surface is more porous, causing localized disintegration of the core and disruption of the
coating. Decrease in spray application rate and use of optimum and efficient drying conditions can solve
this problem.
Pitting is defect in which temperature of the tablet core is greater than the melting point of the materials
used in tablet formulation. Dispensing with preheating procedures at the initiation of coating and
modifying the drying (inlet air) temperature can solve this problem.
Blooming or dull film is generally because of higher concentration and lower molecular weight of
plasticizer. So use lower concentration and higher molecular grade of plasticizer.
Blushing/Whitish specks/Haziness of the film is related to precipitation of polymer exacerbated by the use
of high coating temperature at or above the thermal gelation temperature of the polymers.
Colour variation is because of improper mixing, uneven spray pattern, insufficient coating or migration of
soluble dyes during drying. Geometric mixing, mild drying conditions and reformulation with different
plasticizers can solve this problem.
Infilling is because of bubble/foam formation during air spraying of a polymer solution. Addition of alcohol
or use of spray nozzle capable of finer atomization can solve this problem.
Orange peel/Roughness is related to inadequate spreading of the coating solution before drying. So
decrease in viscosity of coating solution can counter this defect.
Cracking is seen when internal stresses in the film exceeds tensile strength of the film. This is common
with higher molecular weight polymers or polymeric blends. So use lower molecular weight polymers or
polymeric blends

Abdullah - Al - Mamun
PD Officer,
Opsonin Pharma Ltd.