Problems in tablet manufacture and related remedies

Submitted by mukeshgohel on Sun, 12/06/2009 - 19:54

1.10 Problems In Tablet Manufacture
And Related Remedies

What
will you gain?

1.10.1 Introduction

1.10.1.1
Capping

1.10.1.2 Lamination / Laminating

1.10.1.3 Chipping

1.10.1.4 Cracking

1.10.1.5 Sticking / Filming

1.10.1.6 Picking

1.10.1.7 Binding

1.10.1.8 Mottling

1.10.1.9 Double impression

1.10.2 Problems and

Remedies for tablet coating

1.10.2.1 Blistering

1.10.2.2 Chipping

1.10.2.3 Cratering

1.10.2.4 Picking
1.10.2.5 Pitting

1.10.2.6 Blooming

1.10.2.7 Blushing

1.10.2.8 Colour variation

1.10.2.9
Infilling

1.10.2.10
Orange peel/Roughness

1.10.2.11
Cracking/Splitting

1.10.1
Introduction (62,63)

An
ideal tablet should be free from any visual defect or functional defect. The
advancements and innovations in tablet manufacture have not decreased the
problems, often encountered in the production, instead have increased the
problems, mainly because of the complexities of tablet presses; and/or the
greater demands of quality.

An
industrial pharmacist usually 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. Solving many
of the manufacturing problems requires an in–depth knowledge of granulation
processing and tablet presses, and is acquired only through an exhaustive study
and a rich experience.

Here,
we will discuss the imperfections found in tablets along–with their causes and
related remedies. The imperfections are known as: ‘VISUAL DEFECTS’ and they
are
either related to imperfections in any one or more of the following factors:

I. Tableting Process

II. Excipient

III. Machine

The
defects related to Tableting Process are as follows:

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.

The defects related to Excipient are as follows:

iv) CHIPPING: It is due to very dry granules

v) STICKING

vi) PICKING

vii) BINDING

These problems (v, vi, vii) are due to

more amount of binder in the granules or wet granules.

The
defect related to more than one factor:

viii) MOTTLING: It
is either due to any one or more of these factors:

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.

The
defect related to Machine

ix) DOUBLE IMPRESSION: It is due to free rotation of the

punches, which have some engraving on the punch faces.

Further,
in this section, each problem is described along-with its causes and remedies
which may be related to either of formulation (granulation) or of machine
(dies, punches and entire tablet press).

1.10.1.1 Capping (1,5)

Definition:
‘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.

Table.27. The Causes And Remedies Of Capping Related To ‘Formulation’

(Granulation)

Sr. No. CAUSES REMEDIES

1. Large amount of fines in Remove some or all fines

the granulation through 100 to 200 mesh screen

2. Too dry or very low Moisten the granules

moisture content (leading to loss suitably. Add hygroscopic substance
of proper binding action). e.g.: sorbitol, methyl- cellulose or
PEG-4000.
3. Not thoroughly dried Dry the granules properly.
granules.

4. Insufficient amount of Increasing the mount of

binder or improper binder. binder OR

Adding dry binder such as

pre-gelatinized starch, gum acacia,
powdered sorbitol, PVP, hydrophilic
silica or powdered sugar.

5. Insufficient or improper Increase the amount of

lubricant. lubricant or change the type of
lubricant.

6. Granular mass too cold to Compress at room

compress firm. temperature.

Table.28. The Causes And Remedies Of Capping Related To ‘Machine’

(Dies, Punches And Tablet Press)

Sr. No. CAUSES REMEDIES

1. Poorly finished dies Polish dies properly.

Investigate other steels or
other materials.

2. Deep concave punches or Use flat punches.

beveled-edge faces of punches.

3. Lower punch remains below Make proper setting of

the face of die during ejection. lower punch during ejection.
4. Incorrect adjustment of Adjust sweep-off blade
sweep-off blade. correctly to facilitate proper
ejection.

5. High turret speed. Reduce speed of turret

(Increase dwell time).

1.10.1.2 Lamination /
Laminating (1,5)

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.

Table.29. The Causes And Remedies Of Lamination Related To Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

1. Oily or waxy materials in Modify mixing process. Add

granules adsorbent or absorbent.

2. Too much of hydrophobic Use a less amount of

lubricant e.g.: lubricant or change the type of lubricant.
Magnesium-stearate.

Table.30. The Causes And Remedies Of Lamination Related To Machine

(Dies, Punches And Tablet Press)

Sr. No. CAUSES REMEDIES

1. Rapid relaxation of the Use tapered dies, i.e.
peripheral regions of a tablet, upper part of the die bore has an
on ejection from a die. outward taper of 3° to 5°.

2. Rapid decompression Use pre-compression step.

Reduce turret speed and reduce the
final compression pressure.

1.10.1.3 Chipping (1)

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.

Table.31. The Causes And Remedies Of Chipping Related To Formulation

(Granulation) Are As Follows

Sr. No. CAUSES REMEDIES

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 Optimize binding, or use

chipping dry binders.
at bottom.

Table.32. The Causes And Remedies Of Chipping Related To Machine (Dies,

Punches And Tablet Press)

Sr. No. CAUSES REMEDIES

1. Groove of die worn at Polish to open end,
compression point. reverse or replace the die.

2. Barreled die (center of Polish the die to make it

the die wider than ends) cylindrical

3. Edge of punch face turned Polish the punch edges

inside/inward.

4. Concavity too deep to Reduce concavity of punch

compress properly. faces. Use flat punches.

1.10.1.4 Cracking (1)

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.

Table.33. The Causes And Remedies Of Cracking Related To Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

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.

Table.33. The Causes And Remedies Of Cracking Related To Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

1. Tablet expands on ejection Use tapered die.

due to air entrapment.

2. Deep concavities cause Use special take-off.

cracking while

removing tablets

1.10.1.5 Sticking / Filming (1)

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.

Table.35. The Causes And Remedies Of Sticking Related To Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

1. Granules not dried Dry the granules properly.

properly. Make moisture analysis to determine
limits.
2. Too little or improper Increase or change
lubrication. lubricant.

3. Too much binder Reduce the amount of

binder or use a different type of binder.

4. Hygroscopic granular Modify granulation and

material. compress under controlled humidity.

5. Oily or way materials Modify mixing process. Add

an absorbent.

6. Too soft or weak granules. Optimize the amount of

binder and granulation technique.

Table.36. The Causes And Remedies Of Sticking Related To Machine (Dies,

Punches And Tablet Press)

Sr. No. CAUSES REMEDIES

1. Concavity too deep for Reduce concavity to

granulation. optimum.

2. Too little pressure. Increase pressure.

3. Compressing too fast. Reduce speed.

1.10.1.6 Picking (1)

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.

Table.37. The Causes And Remedies Of Picking Related To Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

1. Excessive moisture in Dry properly the granules,

granules. determine optimum limit.

2. Too little or improper Increase lubrication; use

lubrication. colloidal silica as a ‘polishing agent’, so
that material does not cling to
punch faces.

3. Low melting point Add high melting-point

substances, may soften from the materials. Use high meting point
heat of compression and lead to lubricants.
picking.

4. Low melting point Refrigerate granules and

medicament in high the entire tablet press.
concentration.

5. Too warm granules when Compress at room

compressing. temperature. Cool sufficiently before
compression.
6. Too much amount of binder. Reduce the amount of
binder, change the type or use dry
binders.

Table.38. The Causes And Remedies Of Picking Related To Machine (Dies,

Punches And Tablet Press)

Sr. No. CAUSES REMEDIES

1. Rough or scratched punch Polish faces to high

faces. luster.

2. Embossing or engraving Design lettering as large

letters on punch faces such as possible.
as B, A, O, R, P, Q, G. Plate the punch faces with
chromium to produce a smooth and
non-adherent face.

3. Bevels or dividing lines Reduce depths and

too deep. sharpness.

4. Pressure applied is not Increase pressure to

enough; too soft tablets. optimum.

1.10.1.7 Binding (1)

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.

Table.39. The Causes And Remedies Of Binding Related To   Formulation

(Granulation)

Sr. No. CAUSES REMEDIES

1. Too moist granules and Dry the granules properly.

extrudes around lower punch.

2. Insufficient or improper Increase the amount of

lubricant. lubricant or use a more effective
lubricant.

3. Too coarse granules. Reduce granular size, add

more fines, and increase the quantity of
lubricant.

4. Too hard granules for the Modify granulation. Reduce

lubricant to be effective. granular size.

5. Granular material very If coarse granules, reduce

abrasive and cutting into dies. its size.

Use wear-resistant dies.

6. Granular material too Reduce temperature.

warm, sticks to the die. Increase clearance if it
is extruding.

Table.40. The Causes And Remedies Of Binding Related To Machine (Dies,

Punches And Tablet Press)
Sr. No. CAUSES REMEDIES

1. Poorly finished dies. Polish the dies properly.

2. Rough dies due to Investigate other steels

abrasion, corrosion. or other materials or modify granulation.

3. Undersized dies. Too Rework to proper size.

little clearance. Increase clearance.

4. Too much pressure in the Reduce pressure. OR

tablet press. Modify granulation.

1.10.1.8 Mottling (1)

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.

Table.41. The Causes And Remedies Of Mottling

Sr. No. CAUSES REMEDIES

1. A coloured drug used along Use appropriate

with colourless or colourants.
white-coloured excipients.

2. A dye migrates to the Change the solvent system,

surface of granulation while Change the binder,
drying.
Reduce drying temperature
and
 Use a smaller particle
size.

3. Improperly mixed dye, Mix properly and reduce

especially during ‘Direct size if it is of a larger size to prevent
Compression’. segregation.

4. Improper mixing of a Incorporate dry colour

coloured binder solution. additive during powder blending step, then
add fine powdered adhesives such
as acacia and tragacanth and mix well and
finally add granulating liquid.

1.10.1.9 Double
impression (1)

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. Now, on some machines, the lower
punch freely drops and travels uncontrolled for a short distance before riding
up the ejection cam to push the tablet out of the die, now during this free
travel, the punch rotates and at this point, the punch may make a new
impression on the bottom of the tablet, resulting in ‘Double Impression’.

If the upper punch is uncontrolled, it can rotate

during the short travel to the final compression stage and create a double
impression.

Table.42. The Causes And Remedies Of Double Impression

Sr. No. CAUSE REMEDIES

1. Free rotation of either -Use keying in tooling, i.e. inset

upper punch or lower a key alongside of the punch, so
 punch during ejection of a that it fits the punch and prevents punch
tablet. rotation.

-Newer presses have anti-turning devices,

which
prevent punch rotation.

1.10.2 Problems and remedies for

tablet coating
1.10.2.1 Blistering (1,64)

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.

Table.43. The Cause And Remedy Of Blistering

Sr. No. CAUSE REMEDY

1. Effect of temperature on Use mild drying condition.

the strength, elasticity and
adhesion of the film.

1.10.2.2 Chipping (1,64)

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.

Table.44. The Cause And Remedy Of Chipping

Sr. No. CAUSE REMEDY

1. High degree of attrition Increase hardness of the
associated with the coating film by increasing the molecular weight
process. grade of polymer.

1.10.2.3 Cratering (1,64)

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.

Table.45. The Causes And Remedies Of Cratering

Sr. No. CAUSES REMEDIES

1. Inefficient drying. Use efficient and optimum

  drying conditions.

2. Higher rate of application Increase viscosity of

of coating solution. coating solution to decrease spray
application rate.

1.10.2.4 Picking (1,64)

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.

Table.46. The Causes And Remedies Of Picking

Sr. CAUSE REMEDY

No.

1. Inefficient drying. Use optimum and efficient

drying conditions or increase the inlet air
temperature.

2. Higher rate of application Decrease the rater of

of coating solution application of coating solution by increasing
viscosity of coating solution.

1.10.2.5 Pitting (1,64)

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.

Table.47. The Cause And Remedy Of Pitting

Sr. No. CAUSE REMEDY

1. Inappropriate drying Dispensing with preheating

(inlet air ) temperature
procedures at the initiation of coating
and modifying the drying (inlet air)
temperature such that the temperature
of the tablet core is not greater than
the melting point of the batch of
additives used.

1.10.2.6 Blooming (1,64)

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.

Table.48. The Cause And Remedy Of Blooming

Sr. No. CAUSE REMEDY

1. High concentration and low Decrease plasticizer

molecular weight of plasticizer. concentration and increase molecular

  weight of plasticizer.

1.10.2.7 Blushing (1,64)

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.

Table.49. The Causes And Remedies Of Blushing

Sr. No. CAUSES REMEDIES

1. High coating temperature Decrease the drying air

temperature

2. Use of sorbitol in Avoid use of sorbitol with

formulation which causes largest Hydroxy Propyl Cellulose, Hydroxy
fall in the thermal gelation Propyl Methyl Cellulose, Methyl
 temperature of Cellulose
the Hydroxy Propyl Cellulose, and Cellulose ethers.
Hydroxy Propyl Methyl
Cellulose, Methyl
Cellulose and Cellulose ethers.

1.10.2.8 Colour variation (1,64)

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.

Table.50. The Cause And Remedy Of Colour Variation

Sr. No. CAUSE REMEDY

1. Improper mixing, uneven Go for geometric mixing,

spray pattern, insufficient
coating, migration of soluble
dyes-plasticizers
and other additives during
drying.
reformulation with different plasticizers
and additives or use mild drying
conditions.

1.10.2.9 Infilling (1,64)

Definition:
It is defect that renders the intagliations indistinctness.

Reason: Inability of foam, formed by air

spraying of a polymer solution, to break.
The foam droplets on the surface of the tablet breakdown readily due to
attrition but the intagliations form a protected area allowing the foam to
accumulate and “set”. Once the foam has
accumulated to a level approaching the outer contour of the tablet surface,
normal
attrition can occur allowing the structure to be covered with a continuous
film.

Table.51. The Cause And Remedy Of Infilling

Sr. No. CAUSE REMEDY

1. Bubble or foam formation Add alcohol or use spray nozzle

because of air spraying of a capable of finer atomization.
polymer solution

1.10.2.10 Orange peel/Roughness (1,64)

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.

Table.52. The Causes And Remedies Of Orange Peel/Roughness

Sr. No. CAUSES REMEDIES

1. Rapid Drying Use mild drying conditions

2. High solution viscosity Use additional solvents to

decrease viscosity of solution.

1.10.2.11 Cracking/Splitting (1,64)

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.

Table.53. The Cause And Remedy Of Cracking/Splitting

Sr. No. CAUSE REMEDY

1. Use of higher molecular Use lower molecular weight

weight polymers or polymeric polymers or polymeric blends. Also
blends. adjust plasticizer type and
concentration.

Key
Phrases

Ø 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.

Ø Capping and
Lamination are the defects arising as a
result of air-entrapment in the
granular material.

Ø Chipping is a
defect related arising due to very dry
granules.

Ø Cracking is
due to rapid expansion of tablets, when
deep concave punches are used.

Ø Sticking,
Picking and Binding are the
imperfections related to more amount
of binder in
granules.

Ø Mottling is an
imperfection arising due to more than
one factor: a coloured drug, dirt in
granules or the use of an oily lubricant.

Ø 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:

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

Ø 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.

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