Dr.

Sagar N Firke
Dept of Pharmaceutics
Nanded Pharmacy College
Nanded
 CONTENT
 Introduction
 Advantages
 Ideal Characteristics of tablet
 Classification
 Excipients
 Formulation of tablets
 Granulation methods
 Compression mechanism
 Processing Problems
 Equipments & tablet tooling's
 Introduction

 Definition: “tablets are defined as 'solid preparations each

containing a single dose of one or more active ingredients and
obtained by compressing uniform volumes of particles”.

 Tablets are used for systemic delivery and local delivery.

 Advantages:
1. The oral route represents a convenient and safe way of drug

administration.

2.Compared to liquid dosage forms tablets are chemically and

physically stable dosage form.

3. The preparation procedure enables accurate dosing of the

drug.
 4. Tablets are convenient to handle and can be prepared in a
versatile way.

5. Finally, tablets can be produced with robust and quality-

controlled production procedures giving an elegant
preparation.

 QUALITY ATTRIBUTES OF TABLETS

1. The tablet should include the correct dose of the drug.

2. The appearance of the tablet should be elegant and its

weight, size and appearance should be consistent.

3. The drug should be released from the tablet in a controlled

and reproducible way.
4. The tablet should be biocompatible, i.e. not include
excipients, contaminants and microorganisms that could cause
harm to patients.

5. The tablet should be of sufficient mechanical strength to

withstand fracture and erosion during handling.

6. The tablet should be chemically, physically and

microbiologically stable during the lifetime of the product.

7. The tablet should be packed in a safe manner.

 CLASSIFICATION OF TABLETS
 Tablets ingested Orally
1. Compressed Tablets 2. Multiple compressed Tablets
3. Controlled release Tablets 4. Sugar Coated Tablets
5. Film Coated Tablets 6. Chewable Tablets
 Tablets used in Oral Cavity
1. Buccal Tablets 2. Sublingual Tablets
3. Lozenges 4. Dental Cone
 Tablets administered by other routes
1. Implantation Tablets 2. Vaginal tablets
 Tablets used to prepare Solutions
1. Effervescent Tablets 2. Hypodermic Tablets
3. Dispensing Tablets 4. Tablet triturate
 EXCIPIENTS
 Diluent or Fillers
 Lactose

 Molecular formula C12H22O11.

 Often called milk sugar , is a disaccharide found in the milk of
many mammals, including humans and cows.

 It is a sugar composed of Galactose and Glucose subunits.

 The compound is a white, water-soluble, non-hygroscopic solid

with a mildly sweet taste.

 Lactose exist in both crystalline & Amorphous form, crystalline

form is formed by precipitation ( α- Monohydrate)
 Amorphous Lactose can be prepared by spray drying.

 Amorphous Lactose can be dissolve rapidly and has better

compressibility., therefore used in direct compression.

 However it is hygroscopic in nature and physically unstable.

 Lactose may causes Lactose intolerance.

 Mannitol

 Chemical Formula C6H14O6

 Mannitol is a type of sugar alcohol used as a sweetener and
in medication. It occurs naturally, as a sugar or sugar alcohol,
in fruits and vegetables.
 Due to sweet and pleasant taste it is used as filler in
Chewable tablets and Lozenges.
 It has negative heat of solution hence gives cooling sensation
when sucked or chewed.
 It is poorly absorbed from intestine hence used as sweetener
for diabetic persons.
 Microcrystalline Cellulose

 It has molecular formula (C6H10O5)n

 Microcrystalline cellulose is cellulose synthesized from α-

cellulose & obtained as a pulp from fibrous plant material.
 It is prepared by hydrolysis of Cellulose followed by spray
drying. Particle aggregates to form small particles.
 It is insoluble in water, ethanol, ether & slightly soluble in
dilute Sod Hydroxide solution.
 MCC is biocompatible, chemically inert and have good
tabletting and disintegrating properties.
 It is most widely used filler, binder and disintegrant in tablets.
 Disintegrant
 These are the agent which help in the disintegration of the
tablet.
 Disintegrations process occurs in two steps

Fig: Tablet Disintegration Process

 Disintegrant are classified as…..
1. Disintegrant that facilitate water uptake
( Increases the wettablity) Ex: Surfactants
2. Disintegrant that will rupture the tablet
(Caused by swelling of the disintegrant particles)
3. Disintegrant Functions by gas production
( Liberates Carbon dioxide)
Ex: Citric acid and bicarbonate salts
 Disintegrant May be added as intragranular or extragranular.
 Examples are Starch ( Potato, maize and corn starch) (up to
10%), modified starch 1-5 % by weight
 Binders (Adhesives):
 Binders function by providing mechanical strength to the
granules or tablets.

 These can be added differently as dry powder before wet

massing, as solution and as dry powder in slugging.

 These are added in relatively low concentrations at 2 to 10%

by weight.

 Examples: PVP, HPMC, MCC, Crosslinked PVP etc

 Glidants:
 They functions by improving flow property of the powder

 These are important when at high speed production.

 However they are frequently added in the granulation before

tabletting.

 Examples : Talc (1-2 % by weight), Colloidal Silica ( 0.2 % ),

Magnesium stearate ( less than 1%).
 Lubricants:
 The function of lubricant is to facilitate the tablet ejection
with minimum friction with die wall.
 High friction may give rise to several processing problems,
capping or fragmentation.
 Lubrication is achieved by two mechanism fluid lubrication
& boundary lubrication.
 The most effective boundary lubricants are stearic acid and
its salts like magnesium stearate (less than 1%), polyethylene
glycol .
 Lubricants at higher concentrations can adversely affects
particle particle bonding, disintegration and dissolution time
is retarded.
 Drug & fillers should be evaluated for lubricant sensitivity i.e.,
reduction in tablet strength due to addition of lubricant.

 Lubricants should be added by considering r value ( Coefficient

of lubricant efficiency)

 Finer the particle size of the lubricant more effective is the

lubricant.
 Anti adherents:
 These act by reducing adhesion of powder particles and
punch faces, phenomenon called as sticking or picking

 Such adhesion occurs due to moisture content, engraved or

embossed punches.

 Examples: Magnesium stearate, colloidal silica, talc and

starch.

 Sorbents are added to maintain moisture level in the

granulation or in the powder mixture.
 Compression : Is a reduction in bulk volume as a result of
applied load.

 Consolidation: is a phenomenon of increase in mechanical

strength of the consolidated mass.

 Deformation: Change in a geometry due to applied forces,

 Strain: The relative amount of deformation produced by

force called as strain.

 Stress: The ratio of force(F) to cause this strain at area (A)

called stress.
 When external forces are applied to a powder mass, there is a
reduction in its bulk volume because of following reasons.
 Closure repacking of the particles &
 Particle deformation at there point of contact.
 Deformation may be plastic(irreversible) or elastic
(spontaneously reversible)
 CONSOLIDATION

 It is defined as increase in mechanical strength of the

consolidated mass.

 When two particles approach each other closely enough (e.g, at

separation less than 50 nm) their surface free energies result in
strong attractive force, a process known as Cold Welding.

CONSOLIDATION

COLD FUSION
WELDING BONDING
 When applied load is transmitted through the particle
contacts; results in generation of considerable frictional heat.

 If this heat is not dissipated, it causes local rise in temperature

which is sufficient to cause melting of low melting point
substances.
 FORCE DISTRIBUTION

Where,
FA = Is the force applied to the upper
punch.
FL = Proportion of applied force
transmitted to lower punch.
FD = Is the reaction at the die wall.
FR = Radial force.
FA + FL
FM = -----------
2
FM = Mean compaction force
 FORCE DISTRIBUTION
 Effects of friction

1. Interparticulate Friction

2. Die wall Friction

 Interparticulate Friction: This arises at the particle/particle

contacts & expressed as coefficient of Interparticulate
friction. Expressed as µi

 Die Wall Friction: This is due to material being pressed

against the die wall & moved down it is expressed as µw.
 DEVELOPMENT OF RADIAL FORCE

 When the compressive stress is applied in one direction

results in a decrease (ΔH) in the height.

 In the case of unconfined solid body would be

accompanied by expansion in the horizontal direction (ΔD)

 The ratio of two dimensional changes is known as Poisson

ratio λ

λ = ΔD/ΔH
 Consequently radial die wall force (FR) perpendicular to the
die wall surface.
 According to classic friction theory axial frictional force
FD is related to FR by the expression.

Where, µw is coefficient of die wall friction

 Degree of lubrication can be compare by the ratio of FL to FA

i.e., Coefficient of lubricant efficiency. Expressed as R
value.

 The ratio near to unity indicate perfect lubrication (0.98)

& value less than 0.8 indicate poorly lubrication.
  EJECTION FORCES
 Radial die wall forces & die-wall friction affects the ease of
tablet ejection from the die.

 Ejection forces follows three stages.

 Stage1- Peak force required to initiate ejection by breaking

tablet/die-wall adhesion.

 Stage-02- Smaller force is required to push the tablet up

the die.

 Stage03- Final stage is marked by declining force of ejection

as tablet emerges from the die.
Work is required,
 To overcome particulate friction.

 To Overcome friction between particle & machine .

 To induce elastic or plastic deformation.

 To operate various machine parts.

Compression Process Energy Expended (Joules)
Un-lubricated Lubricated
Compression 6.28 6.28
Overcome die wall friction 3.35 Negligible
Upper Punch withdrawal 5.02 Negligible
Tablet Ejection 21.35 2.09
Total Energy 36.00 8.37
 Tablets are made by compressing a formulation containing
a drug with excipients on stamping machine called as
‘presses’

 The components of tablet machine are:

Fig: Hopper Fig: Set of Die & Punch Fig: Feed Frame
 Hopper: For holding of the granules

 Dies: Define the size and shape of the tablet

 Punches: For the compressing the granules within the
dies
 Cam tracks for guiding the movement of the punches.
 Feeding mechanism: distribution of granules from the
hopper into the dies.

Fig: Cam-Tracks
Tablet Tooling

Fig: Compression Punch

 Die Filling: Accomplished by
gravitational flow.

 Tablet Formation: Upper punch

enters the die & powder is
compressed.

 Tablet Ejection: Lower punch

rises until its tip reaches the level
of top of the die.

Fig: Sequence of tablet compression events

 Granules stored in hopper empties into feed frame (A).
 Pull down cam (C) guides the lower punch to the bottom &
dies are allowed to overfill.
 Punches then pass over the weight adjustment cam(E).
 Wipe-off blade (D) at the end of feed frame removes the
excess granules.
 Lower punch travel over the lower compression roll (F).
 Upper punch rides below the upper compression roll(G).
 During decompression upper punch follows raising cam(H).
 The lower punch ride up the cam (I).
 GENERALAPPEARANCE

Tablet Size: Can be determine by Calliper

Shape: Defined by the die shape Color: Micro
reflectance Photometer Presence or absence of odour:
Manual Taste: Taste Panels.
 HARDNESS
“Hardness of tablet has been defined as the force required to
break a tablet in a diametric compression test”
Monsanto Hardness Tester
1.It consist of barrel containing a compressible spring held
between two plungers.
2.The lower Plunger placed in a contact with tablet and
zero reading is taken.
3.The upper plunger is then forced against the spring by
turning threaded bolt until the tablet fractures
4. Conventional tablet have 4-10kg,
 1.It Consist of pairs of Pliers , as the pliers handles are
squeezed, the tablet is compressed between a holding
anvil and piston connected to pressure gauge.
2.The dial indicator remains at the at the reading
where the tablet breaks and it can be returned to zero
pressing reset button.

Fig:
Monsanto
Hardness
Tester

Fig: Pfizer Tester

 FRIABILITYTEST
1. Tablets are subjected to combined effect of abrasion and
shock

2. Apparatus consist of plastic chamber that revolves at 25

RPM dropping the tablets from the distance of 6 inches
with each revolution.

3. Pre-weighed sample is placed in a friabilator which is then

operated for 100 revolutions.

4. Tablets are then dusted and reweighed.

5. Material loss is calculated and expressed as % weight loss

5. Material loss less than 0.5 to 1 % is acceptable.

Fig: Roche Friabilator

1. USP tablet weight variation test is run by weighing 20
tablets individually.

2. Calculate the average weight.

3. Compare the individual weight with average weight.

4. The tablets meet the USP test if no more than two tablets are
outside the given % limit & no tablet differs by more than two
times the given % limit.
Average Weight (mg) Max % difference
allowed
130 mg or less 10
130-324 mg 7.5
More than324 mg 5
Table: Weight variation tolerance for uncoated tablets
Example:

Sr. No Weight Sr. No Weight Sr. No Weight Sr. No Weight

1 350 6 390 11 350 16 340
2 340 7 360 12 325 17 350
3 370 8 355 13 330 18 360
4 360 9 395 14 327 19 370
5 390 10 370 15 340 20 380

Avg Weight = 7152/20= 357.6 mg

5% of the average weight = 357.6 x 5% = 17.88 mg
Upper Limit = Avg weight + 5% = 357.6 + 17.88 = 375.48 mg
Lower limit = Avg weight – 5% = 357.6 -17.88 = 339.72 mg
 CONTENT UNIFORMITY

1. In this test 30 tablets are randomly selected.

2. At least 10 of them are individually assayed.

3. Nine of the 10 tablets must contain not less than

85 % or more than 115 % of the labled drug content.

4. The 10th tablet may contain less than 75 % or more than

125 % of the labeled content.

5. If these requirements are not met, the tablets remaining

from 30 must be assayed & none may fall outside the
given percentage limit.
Def: Disintegration It is a process in which tablet is
breakdown into smaller particles known as disintegration.
Instrument: The USP device consist of a basket having 6
glass tubes.

 Tubes are open at the top and held against 10 mesh screen
at bottom.
 Each tablet is placed in the tube and basket rack is
positioned in 1 L beaker of water, simulated gastric fluid at
37± 2O C.

 A basket assembly moves up and down 5 to 6 cm at a

frequency of 28 to 32 cycles/min.
 Perforated plastic discs may be placed on top of the
tablets, there are useful in low density tablets.

 To be compliance with the USP standards, the tablet must

pass through the 10 mesh screen in the specified time.

Fig: USP Disintegration test apparatus

 DISSOLUTION STUDY
 Testing & interpretation can be continued through three
stages if necessary.
 Six tablets are tested & are acceptable if all of the
tablets are not less than the monograph tolerance
limit(Q) + 5%.

 If tablet fails S1, an additional six tablets are tested(S2).

 The tablets are acceptable if the average of 12 tablets
is greater than or equal to Q & no unit is less than Q-15%.
 If the tablet still fails , an additional 12 tablets are tested.
Tablets are acceptable if the average of all 24 tablets is greater
than or equal to Q& if not more than 2 tablets are less than Q-
Dissolution Test apparatus

Fig: Dissolution test apparatus

 PROCESSING PROBLEMS
1. Capping and Lamination
2. Picking and Sticking
3. Mottling
4. Weight Variation
5. Hardness Variation
6. Double Impression
 Capping and Lamination :
 Capping is a term used to describe the partial or complete
separation of the top or bottom crowns of a tablet from the
main body of the tablet .
Lamination is the separation of a tablet into two or more
distinct layers.

Fig: Capping in tablets Fig: Lamination in tablets

Causes of Capping & Lamination

 Air entrapment during Compression
 Deformational Properties during & following compression
 Stress Relaxation.
 Use of deep concave punches.
 Low Moisture content causes lack of cohesion.
 Curved inward punches causes “claw” formation
 Development of a wear “ring” at the area of
compression in die .
 incorrect setup (Lower punch ejection level) at the press.

Fig: Wear compression ring Fig: Claw like Punches

Picking and Sticking
 “Picking” is a term used to describe the surface material
from a tablet that is ticking to and being removed from the
tablet’s surface by a punch.
 When punch tips have engraving or embossing.
 Small enclosed areas such as those found in the
letters “B,” “A,” and “O”.
 “Sticking” refers to tablet material adhering to the die
wall.
 When sticking occurs, additional force is required to
overcome the friction between the tablet and the die wall
during ejection.
 Fig: Engraving or embossing on the punch

 Serious sticking at ejection can cause chipping of a tablet’s

edges and can produce a rough edge.
 Sticking problem does not allow the lower punches free
movement therefore unusual stresses on the cam tracks and
punch heads, resulting in their damage.
 Excessive moisture may be responsible for sticking.
Remedies
 Lettering should be designed as large as possible..
Chromium plated punches can be used, this will produce a
smooth, nonadherent face.
 Colloidal silica added to the formula acts as a
polishing agent.
 Drying of the granulation is required.
 Mottling
 Mottling is an unequal distribution of color on a
tablet.
Cause of mottling is a drug whose color differs from the
tablet excipients
 Fig: Mottling in tablets
drug whose degradation products are colored.
 A dye can cause mottling by migrating to the surface of a
granulation during drying.
 To overcome this difficulty, the formulator may change the
solvent system, change the binder system, reduce the drying
temperature.
Weight Variation
 The weight of a tablet being compressed is determined
by the amount of granulation in the die prior to
compression.
 Granule Size and Size Distribution Before Compression
 Variations in the ratio of small to large granules.
 Poor Flow
 The die-fill process is based on a continuous and uniform
flow of granulation from the hopper through the feed frame.
The addition of a glidant such as talcum or colloidal
silica, or an increase in the amount already present, may be
helpful.
Depending on the geometry of the hopper, this situation may
causes “arching” or “bridging,” and “rat-holing.”
 When poor hopper flow occurs, it may be controllable
with vibrators attached to the hopper sides to induce the
granulation flow.
Poor Mixing
 It occurs when lubricants and Glidants are not thoroughly
distributed.
Granules do not move efficiently into the dies.
 Inadequate mixing at this stage can result in unsatisfactory
granulation flow.
 Hardness Variation
Hardness depends on the weight of material and the space
between the upper and lower punches at the moment of
compression.