This presentation covers all the aspects of tablets like formulation development, methods of granulation, compression machines, processing problems and quality control test.

1. TABLETS
Dr.P.KOTESWARI
PROFESSOR AND PRINCIPAL
SRIMATHI SAROJINI RAMULAMMA COLLEGE OF
PHARMACY
MAHABUBNAGAR
TELANGANA

2. - At least 90% of all drugs used to produce systemic effects are administered by
oral route.
- Solid dosage-forms represent the preferred class of product
Reasons
- Tablets and capsules represent unit dosage forms
- Liquid dosage forms are expensive to ship
- Breakage or leakage during shipment is another problem with liquids
- Drugs are in general less stable in liquid form, therefore expiration dates
tend to be shorter
- Microbial burden

3. DEF OF TABLET
Tablet is defined as a compressed solid dosage form containing
medicaments with or without excipients. According to the Indian
Pharmacopoeia, Pharmaceutical tablets are solid, flat or biconvex dishes,
unit dosage form, prepared by compressing a drugs or a mixture of
drugs, with or without diluents. They vary in shape and differ greatly in
size and weight, depending on amount of medicinal substances and the
intended mode of administration. It is the most popular dosage form and
70% of the total medicines are dispensed in the form of Tablet. All
medicaments are available in the Tablet form except where it is difficult
to formulate or administer.

4. ADVANTAGES OF
TABLETS
- A tamperproof dosage form
- They are unit dosage form and offer the greatest capabilities of all oral
dosage form for the greatest dose precision and the least content
variability.
- Cost is lowest of all oral dosage form.
- Lighter and compact.
- Easiest and cheapest to package and ship.
- Easy to swallowing with least tendency for hang‐up.
- Sustained release product is possible by enteric coating.
- Objectionable odour and bitter taste can be masked by coating technique.
8. Suitable for large scale production.
- Greatest chemical and microbial stability over all oral dosage form.
- Product identification is easy and rapid requiring no additional steps when
employing an embossed and/or monogrammed punch face.

5. DISADVANTAGES
- Some drugs resist compression into dense compacts, owing to
amorphous nature, low density character.
- Drugs with poor wetting, slow dissolution properties, optimum
absorption high in GIT may be difficult to formulate or
manufacture as a tablet that will still provide adequate or full
drug bioavailability.
- Bitter testing drugs, drugs with an objectionable odour or drugs
that are sensitive to oxygen may require encapsulation or
coating. In such cases, capsule may offer the best and lowest
cost.
- Difficult to swallow in case of children and unconscious patients.

6. PROPERTIES OF
TABLETS
- Should be an elegant product having its own identity while being free
of defects such as chips, discolouration, cracks, contamination and
the like.
- Should have the strength to withstand the rigors of mechanical
shocks encountered in its production, packaging, shipping and
dispensing
- Should have physical and chemical stability
- Must be able to release the medicinal agents in the body in a
predictable and reproducible manner

7. TYPES OF TABLETS
• Tablets ingested orally
• Tablets used in the oral cavity
• Tablets administered by other routes
• Tablets used to prepare solutions

8. TABLETS INGESTED ORALLY
- 90% of the tablets available today are ingested orally
- They are designed to be swallowed intact
Compressed tablets
- These are uncoated tablets made by compression
- They are intended to provide rapid disintegration and drug release
- They are intended to exert local effect(for ex antacids and adsorbents) or
systemic effect
Multiple compressed tablets
- Layered and compression coated tablets
- Both types may be either two component or three component systems, tablet
within a tablet or tablet within a tablet within a tablet
- These are prepared to separate physically or chemically incompatible
ingredients or to produce repeat action or prolonged action products.

9. Repeat action tablets
- Multiple compressed tablets and sugar coated tablets are used for this
purpose
- The core tablet usually coated with shellac or an enteric polymer so that it
will not release its drug load in the stomach. The second dose of the drug is
then added in the sugar coating
Delayed action and enteric coated tablets
- Delayed action tablets are intended to release a drug after some time delay or
after the tablet has passed through one part of GIT into another
- All enteric coated tabs are a type of delayed action tablets
- Enteric tabs are remain intact in the stomach but quickly release in the upper
part of the intestine.
- Enteric coatings are employed for a number safety, therapeutic and medical
reasons. For ex., aspirin tablet may cause gastric upset. Some drugs may
produce nausea and vomiting. Some drugs are destroyed in the stomach

10. Film coated tablets
- Film coating process is an attractive tablet coating method, now polymers
such as HPC and HPMC, which are dissolved in water with an appropriate
plastcizer are now widely used to produce immediate release film coated
tablets
- It offers several advantages like better mechanical strength.
Chewable tablets
- They are intended to be chewed in the mouth prior to swallowing and are not
intended to be swallowed intact
- Most antacid tablets are chewable tablets because of the large dose

11. TABLETS USED IN THE
ORAL CAVITY
Buccal and sublingual tablets
- These tabs are intended to be held in the mouth, where they release
their contents for absorption directly through the oral mucosa
- They are usually small and intended to be held between the cheek
and teeth or in cheek pouch (buccal) or beneath the tongue
(sublingual).
- They should be formulated with the bland excipients, which do not
stimulate salivation
- These tabs are designed not to disintegrate but to dissolve slowly
over a period of 15-30 min in the mouth
- Avoids first pass effect.

12. Troches and Lozenges
-These are used in the oral cavity where they re intended to exert local effect in the
mouth or throat.
-These re commonly used to treat sore throat or to control coughing in the common
cold.
-They my contain local anesthetics, antiseptics, antibacterial agents, demulcents,
and antitussives.
-Lozenges are made with the drug incorporated in a hard sugar candy base by
compression or candy molding process.
-Troches are made by compression as other tablets.
-Both these types of tablets are designed not disintegrate but to dissolve slowly
over a period of 30 or more min.
Dental cones
- These are minor tablets and are designed to be placed in the empty socket
remaining following tooth extration.
-Usual vehicle is sodium bicarbonate, Sodium chloride or an amino acid
-They are formulated to dissolve slowly in the presence of serum or blood over a
period of 20 to 40 min.

13. TABLETS ADMINISTERED
BY OTHER ROUTES
Implants
-They are small, cylindrical or rosette shaped forms and are not more than 8mm
in length and designed for subcutaneous implantation.
-They provide constant drug delivery over a period of one month to one year
-Surgical technique is required for both implantation and removal.
Vaginal tablets
-Theses are designed to undergo slow dissolution and drug release in the vaginal
cavity.
-This tablet form is used to release antibacterial agents, antiseptics or astringents
to treat vagina infections or to releae steroids for systemic absorption

14. TABLETS USED TO
PREPARE SOLUTIONS
Effervescent tablets
-These are designed to produce a solution rapidly with the simultaneous release
of CO2.
-Prepared by compressing the mixture of active ingredient, organic acid and
sodium bicarbonate
-It has a limitation of producing chemically unstable product.
Hypodermic tablets
-These are composed of one or more drugs with the other water soluble
ingredients and are intended to be added to sterile water or water for injection
Tablet triturates
-These are small molded or compressed tablets
Dispensing tablets

15. FORMULATION OF
TABLETS
Compressed tablets usually contain a number of pharmaceutical
adjuncts, known as excipients, in addition to the medicinal substance.
The use of appropriate excipients is important in the development of the
optimum tablets. Excipients determine the bulk of the final product in
dosage forms such as tablet, capsule, etc., the speed of disintegration,
rate of dissolution, release of drug, protection against moisture, stability
during storage, and compatibility . Excipients should have no bioactivity,
no reaction with the drug substance, no effect on the functions of other
excipients, and no support of microbiological growth in the product .

16. DILUENTS
-Diluents are fillers designed to make up the required bulk of
the tablet when the drug dosage is inadequate to produce
this bulk.
The diluents and other excipients must meet the following
criteria.
-Must be non toxic and must be acceptable to the regulatory
agencies
-Commercially available
-Cost effective
-Must be inert & compatible
-Free from microbial load
-No deleterious effect on the bio availability of drug

17. - A classic example for incompatibilities
Tetracycline + calcium phosphate or divalent or trivalent cations
Amine drugs + lactose in presence of magnesium stearate
Lactose
- Low cost and commonly used diluent
-Anhydrous lactose does not undergo millard reaction. But it may picks up the
moisture when exposed to elevated humidity. Such tabs must be packaged
carefully.
Spray dried lactose
-Directly compressible diluent and possess good flow properties
-It is prone to darkening in the presence of excessive moisture, amines and other
compounds due to the presence of a furaldehyde.
Starch
-Ex., wheat, corn or potato starch
Sta-Rx 1500, hydrolyzed starches such as emdex and celutab are free flowing n
directly compressible.

18. Dextrose, mannitol, sorbitol, sucrose and microcrystalline
cellulose
-Mannitol is widely used in chewable tablets because of its
negative heat of solution, its slow solubility and its pleasent
feeling in the mouth. It is non hygroscopic and can be used in
vitamin formulations
- sorbitol is optical isomer of mannitol and combined with mannitol
formulations to reduce diluent cost
-Some of the sucrose based diluents are sugar tab, Dipac, and Nu
tab. all of these are directly compressible diluents.
-MCC is referred to as avicel, directly compressible diluent. Also
acts as disintegrant.
-Di basic calcium phosphate and calcium sulphate can also be
used s diluents

19. BINDERS AND
ADHESIVES
- These materials are added either dry or in liquid form during wet granulation to
promote granules or to promote cohesive compacts for directly compressed
tablets.
Natural gums
- Ex., acacia and tragacanth – 10 to 25% conc alone or in combination
- These materials are variable in composition and performance based on their
natural origin.
- They are heavily contaminated with bacteria
Gelatin
- A natural protein
Starch paste, liquid glucose
Modified natural polymers such as cellulose derivatives
- They can be used in for direct compression, or can be used as aqueous or
alcoholic solutions

20. DISINTEGRANTS
- a disintegrant is added to tablet formulations to facilitate to breakup
or disintegrate the tablet when it contacts water in the GIT.
- Disintegrants may function by drawing water into tablet, swelling
and causing the tablet to burst apart.
- Ex., starch in 5 to 20% of tablet wt, modified starches such as
primogel, explotab, pregelatinized starch
- Clays such as veegum HV and bentonite
- Micro crystalline cellulose.

21. LUBRICANTS, ANTIADHERENTS
AND GLIDANTS
- Lubricants are intended to reduce the friction during tablet ejection between the
walls of the tablet and the walls of die cavity in which the tablet is formed.
- Antiadherents reduce the sticking or adhesion of tablet granulation or powder
to the faces of the punches or to the die wall
- Glidants are intended to promote the flow of the granulation or powder
materials by reducing the friction between the particles.
- Ex., hydrocarbon oils ex., mineral oil
- Production of oil spots
- Stearic acid, stearic acid salts and derivatives are most commonly used.
- Talc
- 5% conc talc is used as glidant, corn starch 5 to 10% conc
- Colloidal silicas such as cab-o-sil, syloid or aerosil in 0.25 to 3%
concentrations can be used as glidants

22. COLOURS, FLAVOURS
AND SWEETENERS
Coloring agent: The use of colors and dyes in a tablet has three purposes:
(1)Masking of off color drugs
(2)Produc tIdentification
(3)Production of more elegant product
All coloring agents must be approved and certified by FDA. Two forms of
colors are used in tablet preparation–FD&C and D&C dyes. These dyes are
applied as solution in the granulating agent or Lake form of these dyes. Lakes
are dyes absorbed on hydrous oxide and employed as dry powder coloring.

23. Example:FD&Cyellow6‐sunsetyellow
FD&Cyellow5‐Tartrazine
FD&Cgreen3‐FastGreen
FD&Cblue1‐BrilliantBlue
FD&Cblue2‐Indigocarmine
D&Cred3‐Erythrosine.
D&Cred22–EosinY
Flavoring agents: For chewable tablet‐flavor oil are used
Sweetening agents: For chewable tablets: Sugar, mannitol.
Saccharine (artificial): 500 time’s sweeter than sucrose
Disadvantage: Bitter aftertaste and carcinogenic
Aspartame (artificial)
Disadvantage: Lack of stability in presence of moisture.

24. MANUFACTURING
METHODS
- The design and manufacture of pharmaceutical tablets is a complex multi-
stage process whereby formulation scientists ensure that the correct amount
of drug substance in the right form is delivered at the appropriate time, at the
proper rate and in the desired location with its chemical integrity protected to
that point. Most drug substances do not possess the required properties which
give satisfactory flow from the hopper to the die cavity of tablet presses. As a
result, they are subjected to pre-treatment either alone or in combination with
suitable excipients to form free-flowing granules that lend themselves to
tabletting.
- Tablets are commonly manufactured by
- wet granulation, dry granulation or direct compression.
- These methods may be considered to consist of a series of steps (unit
processes) – weighing, milling, mixing, granulation, drying, compaction,
(frequently) coating and packaging. Regardless of the method used the unit
processes – weighing, milling and mixing, are the same; subsequent steps
differ.

25. Factors that influence the choice of manufacturing process used
during tablet formulation:
- Compression properties of the Active Pharmaceutical Ingredient (API)/
drug substance
- Physical and chemical stability of the API during the manufacturing
process.
- Particle size of the formulation ingredients.
- Availability of the necessary processing equipment.
- Cost of the manufacturing/formulation process.

26. STEPS INVOLVED IN
MANUFACTURING TABLETS
Dispensing: Each ingredient in the tablet formula is weighed and
accurately dispensed as per dose. This is one of the critical steps
in any type of formulation process and should be done under
technical supervision.
Sizing: Formulation ingredients must be in finely divided form,
otherwise, size reduction should be carried out for better flow
property and easy mixing.
Powder blending: Powders are mixed using a suitable blender to
obtain a uniform and homogeneous powder mix. The drug
substance and excipients are mixed in geometric dilution.
Granulation: Here small powder particles are gathered together
into layers, and permanent aggregates to render them into free-
flowing states.

27. Drying and dry screening: Screened wet granules need to be
dried for a particular time period in tray dry or fluid bed dryer at
controlled temperature not exceeding 550C. Dried granules are
screened through the appropriate mesh screen.
Tablet compression: This step involves the compression of
granules into a flat or convex, round, oblong, or unique shaped,
scored or unscored tablets; engraved with an identifying symbol
and/ or code number using tablet press.
Coating: Tablets and granules are coated if there is need to mask
the unpleasant taste/odour of some drug substance or to increase
the aesthetic appeal of uncoated tablets as well as to modify the
release or control the release of drug substance from tablets. This
is achieved by enclosing or covering the core tablet or granules
with coating solutions.

28. WET GRANULATION
Wet granulation is a widely used method for the production of compressed
tablet. It is essentially a process of size enlargement involving several steps
and the use of an adhesive substance known as binder. The granules
produced using this method of granulation has a greater probability of
meeting all the physical requirements for tablet formation.
A stepwise summary of the manufacturing steps used in the manufacture of
tablets by the wet granulation method are listed below.
Weighing, milling and mixing of the APIs with powdered excipients
(excluding the lubricant)
Preparation of binder solution
Mixing of binder solution with powders to form a damp mass
Screening the dampened powder into pellets or granules (wet screening)
using 6- to 12-mesh screen
Drying of moist granules
Sizing the granulation by dry screening using 14- to 20-mesh screen
Mixing of the dried granules with lubricant and disintegrants
Compression of granules into tablets.

30. DRY GRANULATION
- The formation of granules by compacting powder mixtures into large
pieces or compacts which are subsequently broken down or sized into
granules (often referred to as dry granulation, double compression or
pre-compression
- This method is used when tablet excipients have sufficient inherent
binding properties.
- The procedure can also be used as a means to avoid exposure of drug
substances to elevated temperatures (during drying) or moisture.
- Double compression method eliminates a number of steps but still
includes weighing, mixing, slugging, dry screening, lubrication, and
compression of granules into tablets.
- Compaction for the dry granulation process is generally achieved
either by slugging or roller compaction.

31. Slugging
- In this method, the powder mix is compressed into a soft large flat
tablet (about 1 inch in diameter) using a tablet press that is capable of
applying high stress.
- Following this, the slugs are broken by hand or milled using
conventional milling equipment to produce granules of the required
size.
- Lubricant is added in the usual manner, and the granules then
compressed into tablets.
- Aspirin is a good example of where slugging is satisfactory. Other
materials, such as aspirin combinations, acetaminophen, thiamine
hydrochloride, ascorbic acid, magnesium hydroxide, and other
antacid compounds, may be treated similarly.

32. Roller Compaction
- In roller compaction method, the formulation ingredients are mixed and
are passed between high-pressure (oppositely) rotating rollers that
compress the powder at 1 to 6 tons of pressure.
- The compacted material is then milled to a uniform granule size and
compressed into tablets after the addition of a lubricant.
- The roller compaction method is often preferred to slugging. Excessive
pressures that may be required to obtain cohesion of certain materials may
result in a prolonged dissolution rate.

35. A stepwise summary of the manufacturing steps used in the
manufacture of tablets by the dry granulation method are listed
below.
- Weighing and Milling of formulation ingredients (drug substance and
excipients)
- Mixing of milled powders.
- Compression of mixed powders into slugs.
- Milling and sieving of slugs.
- Mixing with disintegrant and lubricant.
- Compression into tablets.

36. DIRECT
COMPRESSION
- As its name implies, direct compression involves direct compression
of powdered materials into tablets without modifying the physical
nature of the materials itself.
- The technology involved in this method assumes great importance in
the tablet formulations, because it is often the cheapest means,
particularly in the production of generics that the active substance
permits.
- Direct compression avoids many of the problems associated with
wet and dry granulations. Its successful application in tablet
formulation rests on two fundamental issues:
The availability of suitable excipients
The availability of suitable machinery.

38. A stepwise summary of the manufacturing steps used in the
manufacture of tablets by the dry granulation method are listed
below.
- Milling of therapeutic agent and excipients
- Mixing of milled powders, disintegrants and lubricants
- Compression into tablets.
** It is worth noting that tablets produced by direct compression are
often softer than their counterparts that have been produced by wet
granulation and therefore they may be difficult to film-coat.

39. Comparison of various steps used in different
methods of tablet manufacturing processes

40. TABLET
COMPRESSION
Tablets are being formed by compressing the granules by using the
compression machine. Tablet formed in compression machine by
pressing the granules in die with lower and upper punch. Tablet
formation takes place by the combined pressing action of two punches
(lower and upper) and a die.
Now it is possible to produce more than 500,000 tablets per hour due to
different innovations to tablet compression machines.
Basic components of tablet compression machine
- Hopper – for holding and feeding granulation to be compressed
- Dies – define the size and shape of the tablet
- Punches – compress the granulation with in the dies
- Cam tracks – guide the movement of the punches
- A feeding mechanism – for moving granulation from the hopper into
the dies.

41. - Tablet presses are classified into single punch and multi station rotary presses.
- Multi station presses are termed rotary because the head of the tablet machine
that hold the upper punches, dies and lower punches in place rotates
- As the head rotates the punches are guided up and down by the fixed cam
tracks, which control the sequence of filling, compression and ejection.
- The portions of the head that hold the upper and lower punches are called
upper and lower turrets respectively, and the portion holding the dies is called
die table.

44. Different Stages of Tablet Compression Process:
Tablet compression process is divided into four distinct stage.
These stage including filling, metering, compressing and
ejection.
Tablet compressing stage
Filling Formulation is overfilled at the
compressing station
Metering Overfill is removed
Compression Tablet is formed by pressure of punches
within die
Ejection Tablet is ejected from die

46. TABLET TOOLING
CLASSIFICATION OF MULTI-STATION PRESS TOOLING
- The punches and dies is called tablet tooling that determines the shape, size and the identification
markings of the tablets.
- The tooling must meet the specific requirements to satisfy the needs of dosage uniformity,
production efficiency and aesthetic appearance.
- Internationally recognized standards for tablet compression tooling are as follow, i. TSM standard
ii. EU standard
TSM STANDARD
- TSM is acronym for the “TABLET SPECIFICATION MANUAL”, widely recognized and exclusive
in the United States.
- TSM tooling specifications are the sole reference on U.S. manufacturing standards for tablets and
tablet tooling.
- Established by the American Pharmacists Association (APhA)
- TSM tooling specifications are the only published standards for the tablet compression industry.
EU STANDARD
- EU, is short for “EUROSTANDARD” considered as the European standard and also globally
applicable.
- EU, more widely used than the TSM.

47. - The most common tools
employed are referred to as BB
tooling and are 5.25 inches in
length and have a normal barrel
diameter of 0.75inches and 1
inch head diameter
- B tooling is identical to BB type
excpet that the lower punch is
only 3 9/16 inches long
- D tooling is popular for large
tablets utilizing 1 inch barrel
diameter, 11/4 inch head
diameter and 5.25 inch length.
- The dies that are used with the
above punches are either a 0.945
inch outside diameter.

48. PROCESSING
PROBLEMS
Weight variation (granule size and
size distribution)
Poor mixing
Poor flow
Capping and lamination
Picking of tablets
Chipping and splitting
Sticking
Embossing/print defect
Layered tablet splitting/layer not
clearly defined
Low hardness/ low mechanical
strength of tablets/ soft tablets
Variable hardness/ hardness
variation
Mottling
Punch variation
Double impression
Presence of hairs/fibre on tablet
surface
Black spot/stain

49. Capping
- It is the term used, when the upper or lower segment of the tablet separates
horizontally during ejection from the tablet press, or during subsequent
handling
- 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.
- THE CAUSES AND REMEDIES OF CAPPING RELATED TO
‘FORMULATION’ (GRANULATION)
Causes remedies
Large amount of fines in the granulation Remove some or all fines through 100 to 200 mesh screen
Too dry or very low moisture content (leading to loss of proper binding
action).
Moisten the granules suitably. Add hygroscopic substance e.g.: sorbitol,
methyl- cellulose or PEG-4000.
Not thoroughly dried granules. Dry the granules properly.
Insufficient amount of binder or improper binder.
Increasing the mount of binder OR
Adding dry binder such as pre-gelatinized starch, gum acacia,
powdered sorbitol, PVP, hydrophilic silica or powdered sugar.
Insufficient or improper lubricant. Increase the amount of lubricant or change the type of lubricant.
Granular mass too cold to compress firm.
Compress at room temperature.

50. THE CAUSES AND REMEDIES OF CAPPING RELATED TO
‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Poorly finished dies
Polish dies properly. Investigate other steels or
other materials.
Deep concave punches or beveled-edge faces
of punches.
Use flat punches.
Lower punch remains below the face of die
during ejection.
Make proper setting of lower punch during
ejection.
Incorrect adjustment of sweep-off blade.
Adjust sweep-off blade correctly to facilitate
proper ejection.
High turret speed.
Reduce speed of turret (Increase dwell time).

51. Lamination / Laminating
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.
THE CAUSES AND REMEDIES OF LAMINATION RELATED TO
FORMULA
ATION (GRANULATION)CAUSES REMEDIES
Oily or waxy materials in granules
Modify mixing process. Add
adsorbent or absorbent.
Too much of hydrophobic
lubricant e.g.: Magnesium-
stearate.
Use a less amount of lubricant or
change the type of lubricant.

52. The Causes and Remedies of Lamination related to MACHINE (Dies,
Punches and Tablet Press)
CAUSES REMEDIES
Rapid relaxation of the peripheral
regions of a tablet, on ejection from a
die.
Use tapered dies, i.e. upper part of
the die bore has an outward taper of
3° to 5°.
Rapid decompression
Use pre-compression step. Reduce
turret speed and reduce the final
compression pressure.
Chipping
‘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.

53. THE CAUSES AND REMEDIES OF CHIPPING RELATED TO
FORMULATION (GRANULATION) ARE AS FOLLOWS
Causes
REMEDIES
Sticking on punch faces
Dry the granules properly or
increase lubrication.
Too dry granules.
Moisten the granules to
plasticize. Add hygroscopic
substances.
Too much binding causes
chipping at bottom.
Optimize binding, or use dry
binders.

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

55. Cracking: 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.
THE CAUSES AND REMEDIES OF CRACKING RELATED TO
FORMULATION (GRANULATION)
CAUSES
REMEDIES
Large size of granules. Reduce granule size. Add fines.
Too dry granules.
Moisten the granules properly and add proper
amount of binder.
Tablets expand. Improve granulation. Add dry binders.
Granulation too cold. Compress at room temperature

56. CAUSES REMEDIES
Tablet expands on ejection due
to air entrapment.
Use tapered die.
Deep concavities cause
cracking while
removing tablets
Use special take-off.
THE CAUSES AND REMEDIES OF CRACKING RELATED
TO MACHINE (DIES, PUNCHES AND TABLET PRESS)

57. Sticking / Filming
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
THE CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION)
Causes
REMEDIES
Granules not dried properly.
Dry the granules properly. Make moisture analysis to
determine limits.
Too little or improper lubrication. Increase or change lubricant.
Too much binder
Reduce the amount of binder or use a different type of
binder.
Hygroscopic granular material.
Modify granulation and compress under controlled
humidity.
Oily or way materials Modify mixing process. Add an absorbent.
Too soft or weak granules. Optimize the amount of binder and granulation

58. Picking
- ‘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.

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

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

61. - 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.
- THE CAUSES AND REMEDIES OF BINDING RELATED TO
MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Poorly finished dies. Polish the dies properly.
Rough dies due to abrasion,
corrosion.
Investigate other steels or other
materials or modify granulation.
Undersized dies. Too little clearance.
Rework to proper size.
Increase clearance.
Too much pressure in the tablet press. Reduce pressure. OR
Modify granulation.

62. THE CAUSES AND REMEDIES OF BINDING RELATED TO
FORMULATION (GRANULATION)
CAUSES REMEDIES
Too moist granules and extrudes around
lower punch.
Dry the granules properly.
Insufficient or improper lubricant.
Increase the amount of lubricant or use a
more effective lubricant.
Too coarse granules.
Reduce granular size, add more fines,
and increase the quantity of lubricant.
Too hard granules for the lubricant to be
effective.
Modify granulation. Reduce granular
size.
Granular material very abrasive and
cutting into dies.
If coarse granules, reduce its size.
Use wear-resistant dies.
Granular material too warm, sticks to the
die.
Reduce temperature.

63. 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.
A coloured drug used along with
colourless or white-coloured excipients.
Use appropriate colourants.
A dye migrates to the surface of
granulation while drying.
Change the solvent system,
Change the binder,
Reduce drying temperature and
Use a smaller particle size.
Improperly mixed dye, especially during
‘Direct Compression’.
Mix properly and reduce size if it is of a
larger size to prevent segregation.
Improper mixing of a coloured binder
solution.
Incorporate dry colour additive during
powder blending step, then add fine
powdered adhesives such as acacia and
tragacanth and mix well and finally add
granulating liquid.

64. Double impression
‘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.
Free rotation of either upper punch
or lower punch during ejection of a
tablet.
-Use keying in tooling, i.e. inset a
key alongside of the punch, so
that it fits the punch and prevents
punch rotation.
-Newer presses have anti-turning
devices, which prevent punch
rotation.

65. Bridging and rat holing
Product Bridging or “arching” and rat-holing are both issues that result in
a no-flow condition. Bridging, is a case where material that is being
discharged or fed forms a bridge or arch over the feed auger or
discharge point in a silo cone/hopper. Rat-holing is a condition where the
material forms a hole or narrow channel above the feed auger or outlet
in a hopper while the remaining material is stationary against the hopper
wall. Both of these conditions result in the product not flowing as
desired.

66. EVALUATION OF TABLETS
General appearance.
( i ) Size & shape.
(ii) Organoleptic properties.
Weight variation
Content uniformity.
Mechanical strength of tablet.
( i ) Hardness.
(ii) Friability
(iii) Tensile strength.
Disintegration test.
Dissolution test .

67. Why to evaluate tablets? Or quality control
- To ensure safety, potency, efficacy, stability, patient acceptability and
patient compliance of tablet.
- To check wheather a pharmaceutical tablet satisfy certain standards to
claim it to be a quality drug or not.
- To check that the quality parameters are within the acceptance limits
or not.
GENERAL APPEARANCE
- Size & shape: Tablet thickness varies with changes in- ( i ) Die fill, (ii)
Particle size distribution and (iii) Packing of the powder mix being
compressed & with tablet weight.
- The thickness of tablet is measured with a micrometer.
- Tablet thickness should be controlled within a ±5% variation of a
standard value.
- Organoleptic properties Colour (no mottling) Odour (e.g. film coated
tablets). Taste (e.g. chewable tablets).

68. MECHANICAL STRENGTH OF TABLETS
- It provides a measure of the bonding potential of the material concerned and this
information is useful in the selection of excipients . Excessively strong bonds
prevents rapid disintegration & subsequent dissolution. Can be quantified by ( i )
Friability (ii) Hardness or crushing strength
- The friability test is closely related to tablet hardness and is designed to evaluate
the ability of the tablet to withstand abrasion in packaging, handling and shipping.
Friability of a tablet can determine in laboratory by Roche friabilator. This consist
of a plastic chamber that revolves at 25rpm, dropping the tablets through a
Distance of six inches in the friabilator, which is then operate for 100 revolutions.
Remove the tablets from the tray. De- dust and weigh the tablets and note down
the weight of the tablets Calculate the percentage loss in the weight by using the
formula
Percentage Loss =Initial Wt – Final Wt/Initial Wt X 100
F = (Wo – W) / Wo x 100
Where, F = friability Wo = initial weight of tablets W = final weight of tablets
NOTE: Test can be performed by adjusting ‘TIME’ similarly as ‘COUNT’.
Tablet that lose less than 0.5 to 1.0% of the Tablet weight are considered acceptable

70. Hardness test
(a)Monsanto hardness tester (b)Pfizer hardness tester (c)Strong cobb hardness
tester (d)Erweka hardness tester
- Out of the above equipments,Monsanto hardness tester and Pfizer are
commonly used to determine hardness of tablet.
- Monsanto hardness tester: Here, tablet is put between moving jaw and fixed
jaw. Moving jaw is moved and pressure is applied on tablet by means of screw
knob. The point where tablet get break down,it is recorded by means of scale.
The hardness is measured in Kg/cm2.
- Pfizer hardness tester: The Pfizer tester compresses tablet between a holding
anvil and a piston connected to a force-reading gauge when its plier-like
handles are gripped. The point where tablet gets break down, it is noted by
reading gauze.
- Official standards for Hardness: • 5-8 kg/cm2 for standard compressed tablet
except Effervescent tablet, Dispersible tablet, Orodispersible tablet, Chewable
tablet, etc. • More than 8-12 kg/cm2 for Sustain released tablet and controlled
release tablet.

71. Weight variation
20 tablets are weighed individually using an electronic balance. The average
weight is calculated and individual tablet weight will then compared with
average value and the deviation will be recorded
The value of weight variation test is expressed in percentage. The following
formula is used: Weight Variation = (IW - AW)/AW X 100% Where, IW:
Individual weight AW: Average weight
Factors responsible for weight variation: Flow properties Degree of
segregation

82. IPQC (IN PROCESS QUALITY
CONTROL TESTS
In-process quality control (IPQC) tests are strongly related to
final product quality because checks performed during production
in order to monitor and if necessary to adjust the process to
ensure that the product conforms to its specification are the key
for good quality pharmaceutical tablets.
The tests include tablet weight, weight variation, hardness,
thickness, disintegration and various evaluations of elegance.