Problem and Remedies in Tableting PDF

Section 5
Tablet Problems and Remedies

By George E. Reier, PhD
Table of Contents
Tablet Problems and Remedies........................................................................................................1
Table of Contents .........................................................................................................................1
Part A. Specific Tableting Problems and Remedies (Process Format) ........................................5
Dry Blending .............................................................................................................................5
Particle agglomeration .........................................................................................................5
Nonuniformity of mix ............................................................................................................5
Segregation after blending ..................................................................................................6
Wet Granulation (Massing) ........................................................................................................7
Doughy mass........................................................................................................................7
Moisture sensitive drugs ......................................................................................................7
Wet Screening...........................................................................................................................8
Screen clogging....................................................................................................................8
Drying ......................................................................................................................................9
Nonuniform drying ...............................................................................................................9
Granule case hardening (hard crust forms with incomplete drying inside granule) ................9
Color migration ....................................................................................................................9
Drug migration ...................................................................................................................10
Dry Screening (Dry Granulation) ..............................................................................................11
Excess fines .......................................................................................................................11
Difficult to screen................................................................................................................11
Poor color distribution .......................................................................................................12
Feed Hopper ..........................................................................................................................13
Poor flow.............................................................................................................................13
Flooding ..............................................................................................................................14
Particle segregation............................................................................................................14
Tablet Weight .........................................................................................................................15
Weight variation outside limits ..........................................................................................15
Punches and Dies...................................................................................................................16
Punch binding (powder adheres to punch edges and dies; punches may bind in dies) ......16
Punch filming or sticking (picking)(powder adhesion to punch faces, usually upper) ......17
Punch and die abrasion .....................................................................................................18
Capping and laminating .....................................................................................................18
Chipping/splitting ...............................................................................................................19
Score line or tablet imprint not sharp ................................................................................19
Layered tablets splitting .....................................................................................................20
Layers not sharply defined ................................................................................................20
Low hardness .........................................................................................................................20

Variable hardness ...................................................................................................................21
High friability ...........................................................................................................................21
Disintegration too long ...........................................................................................................22
Mottling ...................................................................................................................................22
Tablets contain dirty specks ...............................................................................................23
Tablets uniformly discolored...................................................................................................23
Part B. General Tableting Problems and Remedies (Alphabetical Order Format) ......................24
Active ingredients ...................................................................................................................24
Adsorbents ............................................................................................................................24
Agglomeration of particles .....................................................................................................24
Aging of tablets.......................................................................................................................24
Air entrapment ........................................................................................................................25
Antiadherent ..........................................................................................................................25
Attraction of particles (aggregation or agglomeration) ............................................................25
Binder ....................................................................................................................................25
Binding (bonding or compressibility) .......................................................................................26
Binding in the die (punches) ...................................................................................................26
Bioavailability ..........................................................................................................................26
Bisected or debossed tablets (not sharp or well-defined) ....................................................26
Blending .................................................................................................................................27
Bonding .................................................................................................................................27
Bridging ..................................................................................................................................27
Brittle fracture .........................................................................................................................28
Bulk density ............................................................................................................................28
Capping and laminating .........................................................................................................28
Case hardening.......................................................................................................................29
Chipping/splitting ..................................................................................................................30
Clogging of screen (wet mass) ...............................................................................................30
Coarse particles......................................................................................................................31
Color distribution ....................................................................................................................31
Color migraton........................................................................................................................31
Compressibility .......................................................................................................................31
Content uniformity ..................................................................................................................31
Density, bulk (loose density) .........................................................................................................32
Density, tapped.......................................................................................................................32
Die fill (nonuniform) ..................................................................................................................32
Diluent ....................................................................................................................................33
Dilution potential.....................................................................................................................33
Direct compression.................................................................................................................33
Disintegrant ............................................................................................................................33
Disintegration too long or incomplete....................................................................................34
Disintegration during coating .................................................................................................34
Dissolution ..............................................................................................................................35
Dosage variation.....................................................................................................................35
Doughy mass..........................................................................................................................36
Drug migration ........................................................................................................................36
Dry blending............................................................................................................................36
Dry granulation (by slugging or compaction)...........................................................................37
Dry screening..........................................................................................................................37
Dye migration..........................................................................................................................38
Ejection problem.....................................................................................................................38
Elastic material........................................................................................................................38
Entrapment of air ....................................................................................................................38
Excess fines (wet granulation) .................................................................................................38
Expanding tablets...................................................................................................................39
Filler ....................................................................................................................................39
Filming of punches .................................................................................................................39
Fines (direct compression) .......................................................................................................39
Fines (wet granulation).............................................................................................................39
Flooding ..................................................................................................................................39
Flow problem ..........................................................................................................................40
Friability (high) .........................................................................................................................40
Glidant ....................................................................................................................................41
Granulation, dry ......................................................................................................................41
Granulation, wet .....................................................................................................................41
Hard tablets ............................................................................................................................41
Hardness increases with time ................................................................................................42
Hardness, variable ..................................................................................................................42
High friability ...........................................................................................................................42
High relative humidity .............................................................................................................42
Hopper flow ............................................................................................................................42
Hygroscopic ingredients.........................................................................................................43
Hygroscopic tablets................................................................................................................43
Laminating ..............................................................................................................................43
Layered tablets splitting (poor bonding between layers; layers peel or split apart) .................43
Loss of hardness (with time) ...................................................................................................44
Loss of hardness ....................................................................................................................44
Low to medium level of active (in direct compression)...........................................................45
Lubricants ...............................................................................................................................45
Mixing ....................................................................................................................................45
Modified direct compression..................................................................................................46
Moisture sensitive actives ......................................................................................................46
Mottling ...................................................................................................................................46
Nonuniform die fill...................................................................................................................46
Nonuniform drying (tray drying) ..............................................................................................46
Nonuniformity of mix ..............................................................................................................46
Oleaginous or sticky actives ..................................................................................................47
Ordered mixing (adhesive blending) ........................................................................................47

Overblending ..........................................................................................................................48
Oven drying ............................................................................................................................48
Overwetting of wet mass .......................................................................................................48
Partial direct compression......................................................................................................48
Particle density variation .......................................................................................................48
Particle size distribution .........................................................................................................49
Picking ....................................................................................................................................49
Poor binding ...........................................................................................................................49
Poor color distribution ............................................................................................................49
Poor flow (rat-holing or bridging) .......................................................................................49
Poor granule disintegration ....................................................................................................50
Poor layer demarcation ..........................................................................................................50
Poor tablet finish/appearance ................................................................................................50
Postgranulation addition ........................................................................................................50
Powder separation .................................................................................................................50
Precompression......................................................................................................................51
Punch and die abrasion .........................................................................................................51
Punch binding (powder adheres to punch edges and dies; punches may bind in dies) ..........52
Punch filming or sticking (picking)(powder adhesion to punch faces, usually upper) ..........52
Rat-holing ..............................................................................................................................53
Relative humidity (RH).............................................................................................................53
Roll compacting......................................................................................................................54
Score line or tablet imprint not sharp ....................................................................................55
Screen clogging (wet mass)....................................................................................................55
Segregation.............................................................................................................................55
Slugging ..................................................................................................................................55
Soft tablets ............................................................................................................................56
Splitting (tablets)......................................................................................................................56
Sticking to punch face ...........................................................................................................56
Sticky ingredients ...................................................................................................................56
Tablet binding in the die .........................................................................................................57
Tablets contain dirty specks ...............................................................................................57
Tablets uniformly discolored...................................................................................................57
Underblending .......................................................................................................................57
Variable hardness ...................................................................................................................57
Weight variation (outside limits)...............................................................................................58
Wet granulation.......................................................................................................................58
Part A. Specific Tableting Problems and remedies (Process Format)

Dry Blending
Problem/Concept
Cause/Definition
Remedy/Suggested Solution
Particle agglomeration
Occurs with fine

cohesive powders,
which cause balling
up and poor
distribution
Fine-screen cohesive compound

into bulk mix
Use a more effective mixer (one
with increased shearing action)
Blend the cohesive powder with a
portion (5% to 10%) of an excipient;
screen (mill) if necessary; reblend
and add to the bulk; blend normally
Note: For direct compression excipient
blends do not use a screen size or a
mixer, which will change the excipient
particle size distribution
Nonuniformity of mix
Improper blender load
Use recommended powder load in

blender
Insufficient mixing
Increase mixing time
Inefficient (improper)
mixer
Use alternative mixer with

increased shearing action
Wide particle size

distribution
Select more uniform particle sizes

of components
Overblending
Reduce blending time

Establish optimum mixing
conditions
Low-dosage actives

Problem/Concept
Cause/Definition
(continued)
Low-level excipients
Blend the low-level component

with a portion (5% to 10%) of an
excipient; screen (mill) if
necessary; reblend; add to an
equal quantity of excipient and
mix; screen or mill if necessary;
blend normally with remainder
of bulk
Dissolve drug in a suitable solvent
and add or spray onto a portion
of the bulk or an excipient; blend;
remove solvent
Note: For direct compression
excipient blends do not use a screen
size or a mixer, which will change the
excipient particle size distribution
Segregation after
blending
Particle size
distribution too wide
Use a narrower particle size range

of components
Wet Granulation (Massing)
Problem/Concept
Cause/Definition
Doughy mass
Too much water

(often seen on scaleup)
Add granulating water slowly;

mix well after each addition
Overmixing during
granulation step
Reduce water or mixing time
Wrong binder
Change binder
Component of mix
(e.g., active drug or
excipient)
If possible, use alcohol/water or

alcohol as granulating fluid - select
appropriate binder; use of Avicel
PH-101 gives 1) less sticky or
doughy mass which is easier to
screen; and 2) allows a wider
range of solvent volume
Instability with water
If possible, use ethyl alcohol

or isopropyl alcohol (if latter,
determine acceptable residual
solvent by GC or other appropriate
method) as granulating fluids,
ethyl cellulose and PVP as binders
Moisture sensitive
drugs
Try slugging or roller compaction

as dry granulation methods
Wet Screening
Problem/Concept
Cause/Definition
Screen clogging
Doughy or sticky wet

mass
Avoid oscillating granulator

Use extrusion-type granulator
or Fitz Mill without screens
Reduce granulation time
Add 5% to 20% Avicel PH-101
(gives less sticky or doughy mass,
easier to screen)
Too much water in

mass
Reduce water content; add water

gradually and mix well after each
addition
Mass sensitive to
water content
Incorporate 5% to 20% Avicel

PH-101 (allows a wider range
of solvent volume)
Gummy binder
Change binder
Component or active
ingredient
Use diluted or anhydrous ethyl

solvent level by GC or other
appropriate method); change
binder
Drying
Problem/Concept
Cause/Definition
Nonuniform drying
Poor air circulation

(tray dryer)
Have oven air circulation checked

and corrected
Dryer overload
Reduce number of trays

Reduce thickness of wet mass
on the trays (tray load)
Try fluid bed dryer
Granule case hardening

(hard crust forms with
incomplete drying
inside granule)
Too rapid evaporation

of water
Oven drying
conditions too efficient
Try recirculating oven air (damper

closed) for initial 15 to 30 minutes,
then open damper partially for a
short period, and finally open
damper fully
Reduce drying temperature
Add Avicel PH-101 to formulation
(gives more even water
evaporation and uniform granule
moisture content)
Use a fluid bed dryer
Color migration
Colors migrate to
granule surfaces (wet
granulation); tablets
have mottled
appearance
Use lakes instead of soluble dyes

(will minimize but not eliminate)
Decrease the size of the wet
granules
Decrease thickness of granulation
bed; stir granulation bed frequently
during drying to expose fresh
surfaces at the top of the wet
mass
Use Avicel PH-101- reduces or
eliminates dye migration in wet
granulation
Problem/Concept
Cause/Definition
Drug migration
Drug migrates to
granule surfaces;
content uniformity
problems may result
as drug becomes part
of fines after dry
screening, or there is
a loss of drug with
subsequent low tablet
assays
See remedies under Color

migration
10
Dry Screening (Dry Granulation)
Problem/Concept
Cause/Definition
Excess fines
Granulation overdried
Decrease drying time/temperature

Establish optimum moisture
content
Screen size too small
Use larger screen size
Rotor/screen clearance
too close
Adjust rotor clearance
Overloading of mill or
granulator
Slow feed of material to mill

or granulator
Weak granules
Increase granulating fluid

Increase binder content
Increase wet massing time
Difficult to screen
Granules too hard
Decrease drying temperature

(case hardening)
Decrease water content
(use alcohol/water)
Decrease binder content
Use weaker binder
Moisture in granulation
Increase drying time

content
11
Problem/Concept
Cause/Definition
Poor color distribution
Dye migration to
granule surface
(nonuniformity of
color throughout
granule)

(will minimize but not eliminate
problem)
granules
mass
Use Avicel PH-101- reduces or
eliminates dye migration in wet
granulation
12
Feed Hopper
Problem/Concept
Cause/Definition
Poor flow
Too many fines in wet

granulation
Reduce fines (see Dry screening:

Excess fines)
In direct compression,
particle size of drug or
excipients too small
and/or of shape that
will not flow
Select larger particle size; use

Avicel PH-102 or PH-200 in place
of PH-101 or other excipient
rat-holing
bridging
Add glidant (0.1% to 0.5%)

(e.g., Cab-O-Sil, Aerosil
Use induced or force-feed
mechanism on press
Change particle shape of active
ingredient to one that is more likely
to flow
Poor inherent flow
Add 0.1% to 0.5% glidant

Dry granulate (by slugging or roller
compacting) with a mixture of
Avicel PH-101, Cab-O-Sil ,
and magnesium stearate
Atmospheric moisture
adsorption
Process in low humidity

atmosphere
Add moisture absorber (e.g.,
0.1% to 0.5% calcium silicate,
Cab-O-Sil, Syloid)
13
Problem/Concept
Cause/Definition
Flooding
Excessive flow
properties (fluidization)
of one or more
components (could be
from an excess of
glidant or lubricant)
Identify causative component and

exclude or modify particle size
Flow is erratic and

feed frame is flooded
at times
Use an induced or force-feed

mechanism on press, which may
control flow
Particle size range of

mix too wide

of ingredients
Particle segregation
Select narrow range of particle

sizes; avoid excess fines
See Dry screening: Excess fines

Too wide a density
difference in mix
particles
Control differences in density of

particles
Mixer too vigorous;

produces fines
Use a mixer with a gentler mixing

action
Use of vibrators
(to promote flow from
hopper)
Use force-flow feed mechanisms

rather than hopper vibrators
Excessive machine
vibration
Isolate hopper from tablet machine
14
Table Weight
Problem/Concept
Cause/Definition
Weight variation
outside limits
Poor or erratic powder

flow, flooding
Correct powder flow problem

(See Feed hopper)
Particle size range too

wide
Narrow the particle size range;

avoid excess fines
Use Avicel PH-200 to minimize
weight variation
Particle size not

suitable for die
diameter
Adjust particle size range to

recommended optimum for die
diameter
Punches not within

specifications
Examine punch length dimensions
Particle segregation as
press RPMs increase
Narrow the particle size range

Compress at slower RPM
Lower punch hang up Clean; improve dust collection

(material between lower
punch and die wall or
Check for proper clearance
lower punch and punch
between die wall and lower punch
guide)
Increase lubricant concentration
in formulation
Remove below 200 mesh fines
15
Punches and Dies
Problem/Concept
Cause/Definition
Punch binding (powder

adheres to punch
edges and dies
punches may bind in
dies)
Poor finish or worn

punches and dies
Polish, reface, or replace tooling
Inadequate lubrication
Increase or change lubricant; use

microfine lubricants; screen into
mix
Increase lubricant blending time
Too many fines or

coarse particles in mix
Design better particle size range;

use tapered dies
Wet granulation
insufficiently dried
Dry granulation to satisfactory

moisture limits
Hygroscopic
ingredients
Process under low humidity

conditions
Use moisture scavengers (e.g.,
calcium silicate, Syloid,
Cab-O-Sil)
Adhesive components
Increase lubricant level

Add 0.5% Cab-O-Sil or Syloid
Add 5% to 10% low moisture
grades Avicel PH-112 and
PH-113
16
Problem/Concept
Cause/Definition
Punch filming or
sticking (picking)
(powder adhesion to
punch faces, usually
upper)
Poor finish on punch

faces
Polish punch faces; refinish
Embossed letters
Avoid using certain letters

(e.g., A, B, P, R)
Use shallow embossing with
tapered edges rather than edges
directly perpendicular to punch
face
Punch tips burred
Refinish or replace
Punch concavity too

great
Reduce punch concavity or use

flat face punches
Poor binding between

surface granules or
particles
Increase binder (wet or dry)
Low melting point

ingredient
Adsorb low melting point

ingredient on Avicel, replace with
higher melting point ingredient
Increase or change lubricant

Use microfine lubricants, screen
into mix
Increase lubricant mixing time
Insufficiently dried wet

granulation
Dry granulation and establish

moisture limits
Hygroscopic
components

conditions
Use moisture adsorbent
(e.g., calcium silicate, Syloid)
Adhesive components

or 5% to 10% Avicel PH-101
Tablets too soft
Increase compression pressure
17
Problem/Concept
Cause/Definition
Punch and die abrasion
Abrasive components
Exclude or reduce to a fine particle

size
Blend abrasive component directly
with the lubricant
Use minimum tableting pressure
possible
Use more wear-resistant tooling
(harder metal)
Capping and laminating

Capping is separation of
the top or bottom from
the main body of the
tablet.
Inadequate bonding
of the powder
particles (direct
compression) or
granules (wet
granulation) to form
cohesive tablets
Use a stronger binder or additional

binder
Poor finish or worn

punches and dies
Polish, reface, or replace
Laminating is transverse
cracking and separation
of the tablet into two or
more layers.
Avicel PH-101 and PH-102

are particularly effective direct
compression binders (15% to
25%) and as auxiliary binders
in wet granulation (5% to 15%)
Chrome plate punch faces

Too many fines in
granulation
Modify granulation process for

minimum fines
Granulation too dry

Adjust moisture level and establish
optimum moisture limits
Granulation too wet
(usually associated
with sticking or
picking)
Continue to dry and establish

optimum moisture limit
Overlubrication of
final tableting mix
Decrease lubricant level

Blend lubricant for minimal time
required; establish optimum mixing
time
18
Problem/Concept
Cause/Definition

(continued)
High level of
ingredient with poor
compression
properties (also
sometimes ascribed
to air-entrapment by
powder bed)
Use precompression on tablet

press
Punch concavity too

deep
Change to standard concave

or flat face punches
Punch edges worn or

damaged
Refinish or replace
Lower punch too low

at tablet take-off
Adjust lower punch flush with

die face
Compression too low

in die cavity
Compress in upper portion of

die
Excessive tableting
pressure
Decrease pressure
Die wall binding
Use sufficient lubricant
Slow the speed of the tablet

machine
Use tapered dies

Chipping/splitting
Score line or tablet

imprint not sharp
Poor finish or worn

punches and dies
Polish, reface, or replace punches

and dies
Lower punch setting

too low at tablet
takeoff

die face
Tablet sweep-off
blade on feed frame
set too high
Adjust setting
Faulty punch
debossing design
Redesign using tapered sides

on the punch debossing
Chrome-plate punch face
Granulation too
coarse
Reduce particle size of granulation
Binder not strong

enough
Use a stronger binder
19
Problem/Concept
Cause/Definition
Layered tablets
splitting
Poor bonding
between layers
Use a stronger binder or higher

concentration
Compression
pressure too high
Compress at lower pressures
Overlubrication

required; do not blend for long
periods of time
Layers not sharply

defined
Low hardness
Granulation too
coarse

- less than 16 mesh
Too many fines
Remove fines below 200 mesh
Compression force
(pressure) too low
Increase pressure (caution: do not

exceed recommended pressure
for punch size used)
Overlubrication

time
Replace metallic stearates with
other lubricants (e.g., stearic acid)
Granulation too soft
Use additional binder

Direct compression - use
additional Avicel PH
Excipient (i.e., too

much starch can give
a soft tablet)
20
Reduce level of causative

excipient
Problem/Concept
Cause/Definition
Low hardness
(continued)
Moisture consent too

high (granulation
underdried or high
humidity in
compressing area)
Determine optimum moisture

content
Moisture content too

low (granulation
overdried or low
humidity in
compressing area)
Determine optimum moisture

content
Tooling
Examine punch lengths
Uneven diefill
See Table Weight: Weight

variation
Overblending
Optimize blending time to

minimize creation of fines
Inadequate bonding
of the tablet mix
Increase binder level or change

to stronger binder
Variable hardness
High friability
Use moisture adsorbent (e.g.,

calcium silicate, Syloid)
Add additional moisture
Add or increase Avicel PH-101

or PH-102 (10% to 20%)
Avicel PH gives low friability at
lower hardness/machine pressures
Too much or too little
compression pressure
Adjust pressure for acceptable

friability
Overlubrication

time
21
Problem/Concept
Cause/Definition
Disintegration too long
Tablet hardness too

high
Reduce machine pressure for

acceptable tablets
Use less binder in granulation
Overlubrication
(waterproofing)

time
Requires additional
disintegrant or a
different disintegrant
Consider a super disintegrant

(e.g., Ac-Di-Sol, 2% to 5%)
Include Avicel PH-101 or PH-102
(added dry), about 10% as an
auxiliary disintegrant
Consider adding a surfactant (e.g.,
DOSS, 0.1%)
Mottling
Tablet hardness too

low
Increase hardness to allow

swellable disintegrant to function
Uneven distribution of
the dye in colored
tablets
Increase mixing time or use high

shear mixer
Dye migration during

drying process
See Drying: Color migration

See Dry screening: Poor color
distribution
Preferential
absorption of soluble
dye by component of
mix
High level of
uncolored additives
(e.g., fillers, lubricants,
disintegrants)
22
Replace causative component

Replace soluble dye with microfine
lake pigment
Reduce quantity of additives
Color additives with soluble dye
or mix with lake pigment
Problem/Concept
Cause/Definition
Mottling
(continued)
uneven distribution of
lake dye
Use microfine lake dye

Increase blending time
Mill lake dye with 5% excipient,
then blend with bulk
Reduce size of larger particles
of excipient or active
Use lower drying temperature
Tablets contain dirty

specks
Misaligned upper cam

tracks - rubbing of
punches on cam
actually rubs off metal
which is introduced
into material being
compressed
Check alignment of upper cam

tracks
No lubrication on
upper cam tracks
Tablets uniformly
discolored
Excessive or improper
lubrication on upper
punch shanks (no dust
caps on punches) dust mixes with excess
oil or grease and falls
into material being
compressed
Use dust caps on upper punches
Feed frame rubbing

on die table
Check clearance between feed

frame and die table
Feed hopper rubbing

on turret

hopper and turret
Abrasive materials
wearing screens,
scooper, etc.
Check for presence of abrasive

materials
23
Part B. General Tableting Problems and Remedies

(Alphabetical Order Format)
Problem/Concept
Cause/Definition
Active ingredients
See Sticky ingredients

See Low to medium level
of active
See High percent active
See Attraction of particles
See Dosage variation
See Density
See Elastic material
Adsorbents
Materials used to
overcome oiliness or
stickiness of tablet
ingredients
Use starch, Avicel PH-101,

silicon dioxide (Syloid) or
tribasic calcium phosphate
Agglomeration of
particles
Occurs with fine

cohesive powders
causing "balling" or
lump formation and
poor distribution of
the powder
Fine-screen cohesive compound

into bulk mix
Blend the cohesive powder with
a portion (5% to 10%) of an
excipient; screen (mill) if
necessary; reblend and add to
the bulk; blend normally
Note: For direct compression
excipient blends do not use a
screen size or a mixer, which will
change the excipient particle size
distribution
Aging of tablets
See Loss of hardness (with time)
24
Problem/Concept
Cause/Definition
Air entrapment
Very low density

materials with very
high porosity
(sometimes ascribed
as cause for tablet
capping, splitting,
or laminating)
See Capping and laminating

See Binding
Antiadherent
Materials that aid in

preventing the tablet
mix from sticking to
punch faces
See Section 4 for a description

of excipients and their uses
Attraction of particles
(aggregation or
agglomeration)
Fine cohesive
powders
Modify particle size distribution
Static electricity
Mechanically disperse
Drain off static charge
Low relative humidity
Slightly increase moisture level

See Blending
Densify as last resort
Binder
Wet granulation substances which are

added in solution
(usually) or sometimes
dry, followed by
granulating solvent to
glue a powder mix
into granules for solid
dose preparation
Direct compression substances which give
compressibility or
cohesiveness to the
powder mix
25

Problem/Concept
Cause/Definition
Binding (bonding or
compressibility)
Relative degree of
cohesiveness
between particles or
granules
See Blending
Compressibility of
active ingredients
determines (to some
extent) the percent
that can be
incorporated into a
direct compression
formulation
Optimize particle size and particle

size distribution of active and
excipients
Particular binder and

concentration
influences degree of
binding and tablet
hardness
Binding in the die
(punches)
Bioavailability
Be careful not to overblend or

overlubricate
Use excipients which are

compressible and designed for
direct compression process
Determine that granulation and/or
other excipients have proper
moisture content
See Punch binding

The rate and extent to
which an active
ingredient is absorbed
in-vivo
See Dissolution
Use up to 50% soluble filler
(lactose, dextrose) with insoluble
drugs (direct compression)
May or may not be

correlated with
dissolution
Bisected or debossed
tablets (not sharp or
well-defined)
Poor design on
tooling
Redesign tooling, consult tooling

supplier
Increase binder in formulation
26
Problem/Concept
Cause/Definition
Blending
Mixing of powders to
obtain a homogeneous
mixture (for
compression)
Optimize blending or mixing time
Optimized blending
may depend on type
of mixer (low shear,
high shear, etc.)
Overblending is
probably more
common than
underblending
Overblending causes
overdistribution of the
lubricant which can
result in poor
disintegration/
dissolution, poor
compressibility,
demixing
(segregation)
Bonding
Bridging
See Binding
Lack of powder
fluidity; actual
stoppage of powder
flow as powder
compacts in hopper
or feed-frame
27
See Die fill

See Flow problems
Problem/Concept
Cause/Definition
Brittle fracture
Bonding mechanism
of some materials
(e.g., lactose), in which
single particles fracture
under pressure to
produce multiple
particles having clean
surfaces, which then
bond with each other
to form a compact
See Section 2 for a discussion

of compression mechanisms
Bulk density
See Density, bulk

Capping is separation of
the top or bottom from
the main body of the
tablet.
Laminating is transverse
cracking and separation
of the tablet into two or
more layers.
Inadequate bonding
of the powder
particles (direct
compression) or
granules (wet
granulation) to form
cohesive tablets
Poor finish or worn
punches and dies
Use a stronger binder or additional

binder
Avicel PH-101 and PH-102 are
particularly effective direct
compression binders (15% to
25%) and as auxiliary binders in
wet granulation (5% to 15%)
Polish, reface, or replace
Chrome-plate punch faces
Too many fines in

granulation
Modify granulation process for

minimum fines
Granulation too dry
Adjust moisture level and establish

optimum moisture limits
Granulation too wet

(usually associated
with sticking or
picking)
Continue to dry and establish

optimum moisture limit
Overlubrication of
final tableting mix

time
28
Problem/Concept
Cause/Definition

(continued)
High level of
ingredient with
poor compression
properties (also
sometimes ascribed
to air-entrapment by
powder bed)
Use precompression on tablet

press
Punch concavity too

deep
Change to standard concave or

flat-face punches
Punch edges worn or

damaged
Lower punch too low
at tablet take-off
Refinish or replace
Slow the speed of the tablet

machine

die face
Compression too low

in die cavity
Compress in upper portion of die
Excessive tableting
pressure
Decrease pressure
Die wall binding
Use sufficient lubricant

Use tapered dies
Case hardening
Rapid evaporation of
water, which forms
hard outer crust often
associated with
incomplete drying
inside granules
Try recirculating oven air (damper

closed) for initial 15 to 30 minutes
then open damper partially for a
short period and finally open
damper fully
Reduce drying temperature
Oven drying
conditions too efficient
Add Avicel PH-101 to formulation

(gives more even water evaporation
and uniform granule moisture
content)
Use a fluid bed dryer
29
Problem/Concept
Cause/Definition
Chipping/splitting
Poor finish or worn

punches and dies
Polish, reface, or replace punches

and dies
Lower punch setting

too low at tablet takeoff

die face
Tablet sweep-off
blade on feed frame
Adjust setting
See Binding/bonding
Clogging of screen
(wet mass)
Doughy or sticky wet

mass
Avoid oscillating granulator

Use extrusion-type granulator
or Fitz Mill without screens
Reduce granulation time
(gives less sticky or doughy mass,
easier to screen)
Too much water in

mass
Reduce water content; add water

gradually and mix well after each
addition
Mass sensitive to
water content
Incorporate 5% to 20% Avicel

PH-101 (allows a wider range of
water volume, gives shorter,
less doughy, less sticky mass)
Gummy binder
Change binder
Active ingredient
Use diluted or anhydrous ethyl

solvent level by GC or other
appropriate method); change
binder
30
Problem/Concept
Cause/Definition
Coarse particles
Mottled appearance
in direct compression
Design particle size distribution for

optimum flow, color distribution,
binding
Segregation
Some fines are needed for good

binding
Dye migration leading

to mottling
In direct compression, preblend or

mill color with portion of excipient
Color distribution
In wet granulation, use a dye

soluble in the granulating solution
May help to use a lower
temperature for tray drying; use a
fluid bed dryer
See Color migration
Color migration
Colors migrate to
granule surface
(wet granulation);
will cause mottling
tablets; often
associated with
case hardening

(will minimize but not eliminate)
granules
mass
Use Avicel PH-101- reduces
or eliminates dye migration
Compressibility
See Binding (bonding or

compressibility)
Content uniformity
See Dosage variation
Demixing
Segregation/
separation, usually
caused by overmixing
rather than
undermixing
Optimize blending times specific

to mixer (blender) employed
See Overblending
See Segregation
31
Problem/Concept
Cause/Definition
Density, bulk
(loose density)
Usually defined as the

ratio of weight of a
powder (or mixture of
powders) to its volume
on an as-is basis
(not tapped)
See Flow
Low bulk density often

related to poor flow
especially at high
dosage (active)
Density, tapped
Usually defined as the

ratio of weight of a
powder (or mixture of
powders) to its volume
after being tapped or
caused to consolidate
(settle) in some way
See Die fill

See Dry granulation
Select higher density grades
See Segregation
Too dense can

cause segregation
Die fill (nonuniform)
Lack of consistent
powder flow into dies,
causing variations in
diameter
tablet weight, hardness,
and disintegration/
Reduce fines
dissolution
Add glidant (0.1% to 0.5%) (e.g.,
Cab-O-Sil, Aerosil)
mechanism on press
ingredient to one that is more likely
to flow
32
Problem/Concept
Cause/Definition
Die fill (nonuniform)

(continued)

Avicel, Cab-O-Sil and magnesium
stearate
Process in low humidity atmosphere
Cab-O-Sil, Syloid)
Diluent
Inert material(s)
added to give the
necessary bulk for
solid dosage
preparation

Dilution potential
The percent of an
active (usually poorly
compressible such
as ascorbic acid or
APAP) that can be
compressed with an
excipient to form a
tablet having 1% or
less friability
Avicel PH has a very high dilution

potential when used as a binder
Direct compression
Method of
manufacturing tablets
by compressing
directly a dry blend of
active and excipient
powders; the powders
are neither wet or dry
granulated
See Sections 2 - 4
Disintegrant
Material added to
tablets to aid them in
breaking apart so that
particles of drug can
dissolve

33
Problem/Concept
Cause/Definition
Disintegration too long

or incomplete
Tablet hardness too

high
Reduce machine pressure for

acceptable tablets
Use less binder in granulation
Overlubrication
(waterproofing)

required; establish optimum
blending time
Requires additional
disintegrant or a
different disintegrant
Consider a super disintegrant

(e.g., Ac-Di-Sol, 2% to 5%)
Include Avicel PH-101 or PH-102
(added dry), about 10% as an
auxiliary disintegrant
Consider adding a surfactant
(e.g., DOSS, 0.1%)
Disintegration during
coating
Tablet hardness too

low
Increase hardness to allow

swellable disintegrant to function
Caused by soft cores

or rapidly
disintegrating tablets
Increase tablet strength (increase

binder, add better binder,
compress harder)
Apply a seal coat
(Aquacoat ECD)
If possible, lower spray rate of
aqueous coating
34
Problem/Concept
Cause/Definition
Dissolution
Measure of the rate

and extent to which
an active component
is released into
solution from a drug
product
Use most soluble form of drug

Micronize insoluble drugs - in
general, use smallest particle
size possible
Consider using a wetting agent
May or may not be

correlated with
bioavailability
Add additional disintegrant or a

different disintegrant - granules
must disintegrate for good
dissolution
Poor dissolution
Optimize tablet hardness versus

friability and disintegration/
dissolution
Conduct preformulation studies
to be certain there is no
active/excipient interaction
(binding)
Use a soluble filler with insoluble
actives
Use less lubricant, establish
optimum blending time
See Bioavailability
See Disintegration
Dosage variation
Improper
mixing/segregation
See "Blending, overblending

and demixing"
See Flow problem
See Segregation
See Die fill (nonuniform)
See Nonuniformity of mix
35
Problem/Concept
Cause/Definition
Doughy mass
Too much water

(often seen on
scaleup)
Add granulating water slowly;

mix well after each addition
Overmixing during
granulation step
Reduce water or mixing time
Wrong binder
Change binder
Component of mix
(e.g., active drug or
excipient)
If possible, use alcohol/water

or alcohol as granulating fluid select appropriate binder, use of
Avicel PH-101 gives 1) less sticky
or doughy mass, which is easier
to screen; and 2) allows a wider
range of solvent volume
Drug migration to
surface of granulation
See Color migration
Drug migration
May lead to content

uniformity problems
as drug becomes part
of fines after dry
screening, or there is
a loss of drug with
subsequent low tablet
assays
Dry blending
See Section A: Dry blending
36
Problem/Concept
Cause/Definition
Dry granulation
(by slugging or
compaction)
Method for
compacting powders
by slugging or roller
compaction and then
size reducing the
compacts to the
desired particle size
for tableting
See Section 2
See Slugging
See Roll compaction
Often preferred when

1) it is difficult or
impossible to directly
compress; and 2) the
actives are unstable
when subjected to wet
granulation
Dry screening
Granules too hard
Decrease drying temperature

(case hardening)
Decrease water content (use
alcohol/water)
Decrease binder content
Use weaker binder
Moisture in
granulation
Increase drying time

content
Drying
Overdrying can cause

static flow, case
hardening, drug/color
migration, lamination/
capping/splitting
Underdrying can
cause weak granules
filming, and sticking
of punches
37
Set in-process moisture

specifications on wet granulated
materials
See Section A: Drying
See Section A: Drying
Control moisture in direct
compression excipients for proper
compressibility
Problem/Concept
Cause/Definition
Dye migration
See Color migration
Ejection problem
See Punch binding
Elastic material
Actives or excipients
that are deficient in
plastic flow properties,
and therefore lack
bonding or binding
properties
Use materials that have plastic

flow (low in elasticity) and that,
once compressed, stay
compressed (do not spring
back), such as Avicel PH
Often are springy or

spongy and have
spring back:
characteristics (i.e.,
return to original
size/shape)
Results in capping,
lamination, splitting,
and lack of
compressibility in
general
Entrapment of air
Excess fines
(wet granulation)
See Air entrapment

Low moisture in
granulation
Decrease drying time; establish

optimum moisture content
Screen size too small

(dry screening)
Use larger screen size
Rotor/screen
clearance too close
Adjust clearance of rotor
Overloading
granulator or mill
Feed granulator gradually
Weak granules
Increase binder content/

granulating fluid
Increase wet massing time
Use stronger binder
38
Problem/Concept
Cause/Definition
Expanding tablets

See Active ingredients
See Binding
Filler
Inert material(s)
added to give the
necessary bulk for
solid dosage
preparation
Filming of punches
Fines (direct
compression)

See Punch filming or sticking

(picking)
Poor flow
An optimum percent of fines

serves a useful purpose of dusting
the actives, especially oleaginous
ones or those with elastic
deformation properties, and aids in
in bonding and filling voids within
the tablet
Improper die fill

Poor binding
Too many cause segregation

Fines (wet granulation)
See Excess fines (wet granulation)

See Fines (direct compression)
above
Flooding
Excessive flow
properties
(fluidization) of one or
more components
(could be from an
excess of glidant or
lubricant)
Flow is erratic and
feed frame is flooded
at times
39
Identify causative component and

exclude or modify particle size
Select narrow range of particle
sizes; avoid excess fines
Induced or force-feed mechanism
on press may control flow
See Flow problem
Problem/Concept
Cause/Definition
Flow problem
Too many fines in wet

granulation
Reduce fines (see Dry ScreeningExcess fines)
particle size of drug or
excipients too small
and/or of shape that
will not flow

Add glidant (0.1% to 0.5%), e.g.,
Cab-O-Sil, Aerosil
mechanism on press
ingredient to one that is more
likely to flow
Poor inherent flow
Add 0.1% to 0.5% glidant

Avicel, Cab-O-Sil, and
magnesium stearate
Atmospheric moisture
absorption
Process in low humidity

atmosphere
Cab-O-Sil, Syloid)
Friability (high)
Inadequate bonding
of the tablet matrix
Increase binder level or change to

stronger binder
Add or increase Avicel PH-101
or PH-102 (10% to 20%), which
give low friability at lower
hardness/machine pressures
Too much or too little

compression pressure
40
Adjust pressure for acceptable

friability
Problem/Concept
Cause/Definition
Friability (high)
(continued)
Overlubrication

required; establish optimum
blending time
Glidant
Excipient used to
improve fluidity of
powders
See Section 4
Add 0.1% to 0.5% Cab-O-Sil or
Aerosil fumed silica to improve
flow
Small increase in lubricant may be
necessary to offset slight punch/die
binding effect of glidant
Granulation, dry
See Dry granulation

See Section 2
Granulation, wet
See Wet granulation

See Section 2
Hard tablets
Use Avicel to obtain hard tablets

with low machine pressure - also
to reduce tablet friability
compressibility)
Decrease compressing speed
to increase tablet hardness
41
Problem/Concept
Cause/Definition
Hardness increases
with time
Probably more
prevalent in wet
granulated products,
although it can
happen in directly
compressed tablets
Optimize moisture consent

of granulations
Can be caused by
water of crystallization/hydration
interacting with
ingredients or other
kinds of interactions
between active
materials/excipients
Hardness, variable
Tooling
Uneven die fill
See Weight variation
Overblending
Optimize blending time to minimize

creation of fines
High friability
High level of active
Conduct preformulation studies,

even though data at accelerated
temperature/ humidity conditions
may not always be relevant to
shelf-life conditions
See Friability (high)

Direct compression
High percentages of actives can be

directly compressed depending on
physical form (low density,
entrapped air, etc.), flow, and
compressibility properties
Dry/wet granulation
If unable to compress directly, dry

granulation or wet granulation are
possible alternatives depending on
active's physical properties
High relative humidity
See Relative humidity
Hopper flow
See Die fill

See Flow Problem
See Segregation
42
Problem/Concept
Cause/Definition
Hygroscopic
ingredients
Moisture pick-up

conditions
Compress with low moisture grades
Cab-O-Sil)
Hygroscopic tablets
Moisture pick-up
Compress and package underlow

humidity conditions (to maintain
tablet hardness and active
ingredient stability)
Cab-O-Sil)
Keep tablet containers well closed
(use adequate closures especially
if plastic or blister packed)
Laminating
Layered tablets
splitting (poor bonding
between layers; layers
peel or split apart)

Poor bonding
between layers
Use a stronger binder or higher

concentration
Compression
pressure too high
Compress at lower pressures
Overlubrication

times
See Lubricants
43
Problem/Concept
Cause/Definition
Loss of hardness
(with time)
Tablets with Avicel PH

lose some hardness
with time at high
humidity, but most of
the hardness is quickly
regained at normal
humidity
See Hygroscopic ingredients
Compression force
(pressure) too low
Increase pressure (caution - do not

exceed recommended pressure for
punch size used)
Overlubrication
Low hardness
See Hygroscopic tablets

times
Granulation too soft
Use additional binder

Direct compression - use additional
Avicel PH
Excipient (i.e., too

much starch can give
a soft tablet)
Reduce level of causative excipient

high
Granulation underdried
High humidity-use moisture
scavenger or moisture adsorbent
(e.g., calcium silicate, Syloid)

low
Granulation overdried
Low humidity-direct compression
excipients too low in moisture
content
44
Problem/Concept
Cause/Definition
Use 10% to 20% Avicel PH
combined with compressible
lactose and/or dicalcium phosphate
Low to medium level

of active (in direct
compression)
With higher levels of Avicel PH use

less magnesium stearate, since
Avicel PH is self-lubricating
At low-dosage level-blend or mill
active with part (e.g., 10% of
excipient) and then blend with
remainder of formulation
At very low-dosage levels (<1%),
dissolve active in solvent and spray
on excipients
Lubricants
Materials added to
reduce friction
between the die wall
and the tablet mix,
and hence facilitate
ejection of the tablets
from the die
See Section 4 for a description of

excipients and their uses
See Punch binding
Add lubricant at end of blending
operation-do not overblend
Screen into bulk powders through a
40- to 60-mesh screen prior to final
mixing
If disintegration/dissolution is a
problem with magnesium stearate,
use stearic acid (1% to 2%)
With higher levels of Avicel PH use
less magnesium stearate (since
Avicel PH is self-lubricating)
Mixing
See Blending
See Section A, Dry blending
45
Problem/Concept
Cause/Definition
Modified direct
compression
Modification of direct
compression process
to assure good
dispersion of low-level
actives or for other
reasons
Dissolve actives in volatile solvents

and spray onto excipients
Avoids granulation of
entire formulation
Moisture sensitive
actives
Unstable in the
presence of water
Granulate a small portion of the

formulation and directly compress
this granulation with the remainder
(major part) of the formulation
ingredients
Use direct compression or dry
granulation
Use low moisture grades Avicel
PH-112 and PH-113
Use nonaqueous granulating
solvent (flammability and residual
solvent cautions must be observed)
Mottling
See Color distribution
Nonuniform die fill
See Diefill (nonuniform)
Nonuniform drying
(tray drying)
Poor air flow

(circulation)
Correct air circulation pattern

Reduce number of trays
Overloaded trays
Reduce tray load

See Drying
Improper blenderload
Use recommended powder load

in blender
Insufficient mixing
Increase mixing time
Inefficient (improper)
mixer
Use alternative mixer with increase

shearing action
Wide particle size

distribution
Select more uniform particle sizes

of components
Overblending
Reduce blending time

Establish optimum mixing
conditions
46
Problem/Concept
Cause/Definition
(continued)
Low-dosage actives

Low-level excipients
Blend the low-level component with

a portion (5% to 10%) of an
excipient; screen (mill) if necessary;
reblend; add to an equal quantity of
excipient and mix; screen or mill if
necessary; blend normally with
remainder of bulk
Dissolve drug in a suitable solvent
and add or spray onto a portion of
the bulk or an excipient; blend;
remove solvent
Note: For direct compression excipient
blends do not use a screen size or a
mixer which will change the excipient
particle size distribution
Oleaginous or sticky
actives
See Punch binding

See Sticky ingredients
Ordered mixing
(adhesive blending)
Small-sized (drug)
particles adhesively
held on the surface of
larger-sized
(excipient) particles
Segregation does not
occur
Usually requires a
high-intensity mixer
47
See Section 2
Problem/Concept
Cause/Definition
Overblending
Can cause powder

separation
(segregation or
demixing)
Optimize mixing times

See Blending
Can cause particle

size reduction leading
to other problems
Can cause
waterproofing of
tablet by lubricant
Oven drying
Overwetting of
wet mass
See Drying
A common problem in
wet granulation
See Clogging of screen
Some actives alone

and in combination
with excipients are
more sensitive than
others (due to
solubility)
Partial direct
compression
See Modified direct compression
Particle density
variation
See Density, bulk (loose density)

See Density, tapped
See Punch binding
48
Problem/Concept
Cause/Definition
Particle size
distribution

compressibility)
See Flooding
`See Flow problem
See Ordered mixing (cohesive
blending)
See Segregation
Picking
Tablet surfaces
pitted
Small areas of
compressed powder
left on punch faces
(mostly upper) after
compression - tablet
surface is picked
Often associated with
punch filming and
sticking
Poor binding

compressibility)
Poor color distribution

See Color migration
Poor flow (rat-holing

or bridging)
See Flow problem
49
Problem/Concept
Cause/Definition
Poor granule
disintegration
Wet granulation
Granules must be disintegrated

for prompt and full drug release
(dissolution)
Include a portion (50%) of the
disintegrant (Ac-Di-Sol) for this
purpose in the materials being
granulated (disintegrant inside
the granulation)
Poor layer demarcation
Poor tablet
finish/appearance
Postgranulation
addition
Granulation too
course
Reduce particle size of

granulation - less than 16 mesh
Too many fines
Remove fines below 200 mesh
Picking
See Filming of punches
Mottling
Coarse particles
See Coarse particles
Excipients added after

drying the granules
and screening them
See Sections 2 and 4
Examples: disintegrant,
lubricant, additional
binder
Powder separation

See Demixing
See Flow problem
See Overblending
See Segregation
50
Problem/Concept
Cause/Definition
Precompression
Application of a
relatively small
amount of tableting
pressure immediately
prior to application of
main tableting
pressure
See Section 3
Aids in removing
entrapped air
Aids in preventing/
minimizing capping/
laminating of difficultto-compress materials
by allowing time for
relaxation between
compressions
Requires a rotary
tablet machine
equipped for
precompression
Punch and die abrasion
Abrasive components
Exclude or reduce to a fine particle

size
Blend abrasive component
separately with the lubricant
Use minimum tableting pressure
possible
Use more wear-resistant tooling
(harder metal)
51
Problem/Concept
Cause/Definition
Punch binding (powder

adheres to punch
edges and dies,
punches may bind
in dies)
Poor finish or worn

punches and dies
Polish, reface or replace tooling
Increase or change lubricant; use

microfine lubricants; screen into
mix
Increase lubricant blending time
Too many fines or

coarse particles in mix
Design better particle size range;

use tapered dies
Wet granulation
insufficiently dried
Dry granulation to satisfactory

moisture limits
Hygroscopic
ingredients
Process in low humidity conditions

Cab-O-Sil)
Use low moisture grades
Adhesive or
oleaginous
components

Punchfilming or
sticking (picking)
(powder adhesion to
punch faces, usually
upper)
Poorfinish on punch
faces
Polish punch faces; refinish
Embossed letters
Avoid using certain letters (e.g.,

A, B, P, R)
Use shallow embossing with
tapered edges rather than edges
perpendicular to punch face
Punch tips burred
Refinish or replace
Punch concavity too

great
Reduce punch concavity or use

flat-face punches
Poor binding between

surface granules or
particles
Increase binder (wet or dry)
Low melting point

ingredient
Adsorb low melting point ingredient

on Avicel PH, replace with higher
melting point ingredient
52
Problem/Concept
Cause/Definition
Punch filming or
sticking
(continued)
Increase or change lubricant

Use microfine lubricants, screen
into mix
Increase lubricant mixing time
Insufficiently dried wet

granulation
Dry granulation and establish

moisture limits
Hygroscopic
components

conditions
Use moisture adsorbent (e.g.,
calcium silicate, Syloid)
Adhesive components

or 5% to 10% Avicel PH-101
Rat-holing
Tablets too soft
Increase compression pressure
Limited flow of a
powder or mixture
directly over the
discharge of a hopper,
leaving a hole in the
center of the powder
as flow slows or stops
See Bridging
See Flow problem
See Glidant
Part of the remaining

powder, which is
around the hole, may
fall into the hole with
the net result being
an uneven flow of
powder and/or lumps
from the hopper
Relative humidity (RH)
Ratio of the amount of

water the air is holding
to the amount it could
hold (at saturation) at a
given temperature
53
Keep tableting area <55% RHhigher RH can cause flow problems

and sticking depending on
materials present
Problem/Concept
Cause/Definition
Relative humidity (RH)

(continued)
Raising the
temperature, all other
things remaining
constant, lowers the
relative humidity but
the absolute amount
of water present is
the same
Keep tableting area >40% to 45%

RH - lower humidity can cause flow
because of static and drying out of
material being compressed with,
perhaps, some loss of
compressibility
See Hygroscopic ingredients
See Hygroscopic tablets
Roll compacting
Forcing powder
(almost always a
formulation containing
filler, lubricant, and
disintegrant) between
two oppositely turning
rolls in order to form a
dense compact in the
form of a relatively flat
sheet as it exits the
rolls
The sheet (which often
breaks under its own
weight as it exits the
rolls) is milled to form
granules, which can
then be used for
tableting after adding
additional lubricant,
disintegrant, etc.
54
See Section 2
Use Avicel PH-101
Problem/Concept
Cause/Definition
Score line or tablet

imprint not sharp
Faulty punch
embossing design
Redesign using chamfered edges

on the punch embossing
Chrome-plate punch face
Granulation too
coarse
Binder not strong

enough
Use a stronger binder
Screen clogging
(wet mass)
Segregation
See Clogging of screen (wet mass)

Particle size range of
mix too wide

of ingredients
Limit the amount of the fines present
Slugging
Too wide a density

difference
Control differences in the density

of particles
Mixer too vigorous,

produces fines
Use a mixer with a gentler mixing

action
Use of vibrators (to

promote flow from
hopper)
Use force-feed mechanisms rather

than hopper vibrators
Use of relatively large

punches and dies to
produce tablets from
a poor flowing powder
mix
See Dry granulation
Tablets usually not

well-controlled with
respect to weight
and hardness
55
Problem/Concept
Cause/Definition
Slugging (continued)
Tablets milled to
produce granules
which can then be
used (after adding
additional lubricant,
disintegrant, etc.)
to produce uniform
tablets of desired
size, weight,
hardness, etc.
Soft tablets

compressibility)
See Excess fines (wet
granulation)
See Friability (high)
See Hardness, variable
See Loss of hardness (with time)
See Low hardness
Splitting (tablets)

See Chipping/splitting
Sticking to punch face
Sticky ingredients
Fines in excipient mix (especially

Avicel PH) aid in drying up
oleaginous actives, giving better
flow and tableting
See Punch binding
56
Problem/Concept
Cause/Definition
Tablet binding
in the die
Tablets contain dirty
specks
See Punch binding

Misaligned upper cam
tracks - rubbing of
punches on cam
actually rubs off metal,
which is introduced
into material being
compressed
Check alignment of upper cam

tracks
No lubrication on
upper cam tracks
Tablets uniformly
discolored
Excessive or improper
lubrication on upper
punch shanks (no dust
caps on punches) dust mixes with excess
oil or grease and falls
into material being
compressed
Use dust caps on upper punches
Feed frame rubbing

on die table

frame and die table
Feed hopper rubbing

on turret

hopper and turret
Abrasive materials
wearing screens,
scooper, etc.
Check for presence of abrasive

materials
Underblending
Variable hardness
See Blending
Tooling
Uneven die fill
See Weight variation
Overblending
Optimize blending time to

minimize creation of fines
57
Problem/Concept
Cause/Definition
Weight variation
(outside limits)
Poor or erratic powder

flow, flooding
Correct powder flow problems

(See Feed Hopper in Part A)
Particle size range too

wide
Narrow the particle size range;

avoid excess fines
Particle size not

suitable for die
diameter

diameter
Punches not within

specifications
Examine punch length dimensions

Narrow the particle size range
Particle segregation
as press RPMs
increase
Compress at slower RPM

Clean; improve dust collection
Lower punch hang

up (material between
lower punch and die
wall or lower punch
and punch guide)
Check for proper clearance

between die wall and lower punch
Increase lubricant concentration
in formulation
Remove below 200 mesh fines
Wet granulation
Process whereby
active drugs and
excipients are wet
massed (wet with
a solvent containing
a binder in solution,
usually), screened,
dried, and screened
again
Used for high-dose
active drugs which
have poor flow and
either cannot be or
are difficult to directly
compress
Used for active drugs
which are very fine
and/or low density
58
See Section 2
FMC logo, Avicel, Aquacoat and Ac-Di-Sol trademarks of FMC Corporation.

Aerosil trademark of Degussa Aktiengesellschaft.
Cab-O-Sil trademark of Cabot Corporation.
Fitz Mill trademark of Fitzpatrick Company, The Illinois Corporation.
Syloid trademark of W.R. Grace & Co. Connecticut.
1998 FMC Corporation. All rights reserved. RS
59

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Section 5

Tablet Problems and Remedies

Low hardness .........................................................................................................................20

Ordered mixing (adhesive blending) ........................................................................................47

Part A. Specific Tableting Problems and remedies (Process Format)

Occurs with fine

Fine-screen cohesive compound

Improper blender load

Use recommended powder load in

Increase mixing time

Use alternative mixer with

Wide particle size

Select more uniform particle sizes

Reduce blending time

Use a more effective mixer (one

Blend the low-level component

Use a narrower particle size range

Wet Granulation (Massing)

Too much water

Add granulating water slowly;

Reduce water or mixing time

If possible, use alcohol/water or

Instability with water

If possible, use ethyl alcohol

Try slugging or roller compaction

Doughy or sticky wet

Avoid oscillating granulator

Too much water in

Reduce water content; add water

Incorporate 5% to 20% Avicel

Use diluted or anhydrous ethyl

Poor air circulation

Have oven air circulation checked

Reduce number of trays

Granule case hardening

Too rapid evaporation

Try recirculating oven air (damper

Use lakes instead of soluble dyes

See remedies under Color

Dry Screening (Dry Granulation)

Decrease drying time/temperature

Screen size too small

Use larger screen size

Adjust rotor clearance

Slow feed of material to mill

Increase granulating fluid

Granules too hard

Decrease drying temperature

Increase drying time

Poor color distribution

Use lakes instead of soluble dyes

Too many fines in wet

Reduce fines (see Dry screening:

Select larger particle size; use

Add glidant (0.1% to 0.5%)

Poor inherent flow

Add 0.1% to 0.5% glidant

Process in low humidity

Identify causative component and

Flow is erratic and

Use an induced or force-feed

Particle size range of

Use a narrower particle size range