1

Lecture: 2

Tablet Manufacturing

By Desta T. 06/27/2025
 Objective
2

 At the end of this lesson Students will able to answers :

 What is tablet?
 What are the most critical features of the tablet manufacturing
process.?
 What are Tablet manufacturing Mechanism?
 How tablet quality are assured?

By Desta T. 06/27/2025
 Introduction
3
 Tablets: are the most common solid pharmaceutical dosage
forms containing one or more drug substances.
 Tablets have been in wide spread use since the latter part of the
19th century and their popularity continues.
 They are intended for oral administration.
o swallowed whole,

o being chewed,

o dissolved or dispersed in water before use and

o retained in the mouth

By Desta T. 06/27/2025
 Advantages of tablets
4
 Correct dosing is possible because tablets contain unit doses
 Easy to carry by the patient
 Relatively long shelf life unlike liquid dosage forms
 Flexibility to manufacturing
 Release of drug can be modified e.g enteric-coated tablets,
sustained-release tablets, etc
 Easy identification by color, emboss, etc

By Desta T. 06/27/2025
 Disadvantages of tablets
5
 Some drugs resist compression into dense compacts
 Drugs with poor wetting, intermediate to large dosages may
be difficult or impossible to formulate and manufacture as a
tablet that provide adequate or full drug bioavailability

 Bitter taste drugs,

 difficult to administer to infants and old people

By Desta T. 06/27/2025
 Quality attributes of
6
tablets

 The quality attributes of a tablet

 The tablet should contain the correct dose of the drug.
 Its should be elegant and its weight and size should be
consistent.
 The drug should be released from the tablet in
reproducible way.

By Desta T. 06/27/2025
 Quality attributes of
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tablets…….Cont’d
 The tablet should be biocompatible, i.e. not include
contaminants and microorganisms that could cause harm to
patients.
 It should be of sufficient mechanical strength to withstand
fracture and erosion during handling.
 The tablet should be chemically, physically and
microbiologically stable during the lifetime of the product.
 The tablet should be packed in a safe manner.

By Desta T. 06/27/2025
 Tablet Ingredients
8

 In addition to the active or therapeutic ingredient, tablets

contain a number of inert materials.
 The first group contains those that help to impart satisfactory
processing and compression characteristics to the
formulation.
 These include diluents, binders, glidants, lubricants, and
antiadherents.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
9

 The second group of added substances helps to give

additional desirable physical characteristics to the finished
tablet.
 Included in this group are disintegrants, surfactants, colors and,
flavors, and sweetening agents.
 In some cases, antioxidants or other materials can be added to
improve stability and shelf-life

 Diluents (or fillers)

 Frequently, the single dose of the active ingredient is small,
and an inert substance is added to increase the bulk to make
the tablet a practical size for compression.
By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
10
 Diluents used for this purpose include dicalcium phosphate,
calcium sulfate, lactose, cellulose, kaolin, mannitol, sodium
chloride, dry starch, and powdered sugar.

 Certain diluents, such as mannitol, lactose, sorbitol, sucrose,

and inositol, when present in sufficient quantity, can impart
properties to some compressed tablets that permit disintegration
in the mouth by chewing.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
11

 When drug substances have low water solubility, it is

recommended that water-soluble diluents to be used to avoid
possible bioavailability problems.
 Highly adsorbent substances (eg, bentonite and kaolin) are to be
avoided in making tablets of drugs used clinically in small
dosage, such as cardiac glycosides, alkaloids, and the synthetic
estrogens.
 The combination of amine salts with lactose in the presence of
an alkaline lubricant results in tablets that discolor on ageing
( they undergo Millard reaction).

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
12

 Many ingredients are used for several different purposes, even

within the same formulation(e.g., corn starch can be used in
paste form as a binder).
 When added in dry or suspension form, it is a good disintegrant.

 Binders
 Agents used to impart cohesive qualities to the powdered
material are referred to as binders or granulators.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
13
 They impart a cohesiveness to the tablet formulation that
ensures
o the tablet remaining intact after compression,

o improving the free flowing qualities by the formulation of

granules of desired hardness and size.

 Materials commonly used as binders include starch, gelatin, and

sugars such as sucrose, glucose, and lactose.
 Natural and synthetic gums that have been used include acacia,
sodium alginate, carboxymethylcellulose, methylcellulose,
polyvinylpyrrolidone
By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
14
 The use of too much binder or too strong a binder will make a
hard tablet that will not disintegrate easily and will cause
excessive wear of punches and dies.

 Alcohol and water are not binders in the true sense of the word,
but because of their solvent action on some ingredients such as
lactose, starch, and cellulose, they change the powdered
material to granules, and the residual moisture retained enables
the material to adhere together when compressed.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
15
 Binders are used as a solution and in dry form, depending on the
other ingredients in the formulation and the method of
preparation.

 The same amount of binder in solution will be more effective

than if it were dispersed in a dry form and moistened with the
solvent.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
16
 The most commonly used binders include:
o Starch paste- Corn starch is widely used as binder.
 It usually is prepared as it is to be used, by dispersing corn

starch in sufficient cold purified water to make a 10-20%

w/w suspension and warming in a water bath with continuous
stirring until a translucent paste forms.
o Gelatin solution- Gelatin generally is used as a 10-20%
solution. Gelatin solution should be prepared freshly as needed
and used while warm or they will solidify

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
17
o Cellulosic solutions- Various cellulosics have been used as
binders in solution form.
 HPMC has been widely used in this regard. It is more

soluble in cold water than hot.

 Other water soluble cellulosics such as HEC, HPC have

been used successfully in solution as binders.
 EC is not soluble in water but dissolves in alcohol.
 It is used as a binder for materials that are moisture-sensitive.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
18
 Polyvinylpyrrolidone – PVP can be used as an aqueous or
alcoholic solution and this versatility has increased its
popularity.
 Disintegrants
 A disintegrant is a substance or a mixture of substances

added to a tablet to facilitate its breakup or disintegration

after administration.
 Materials serving as disintegrants are starches, clays,

celluloses, algins, gums, and cross-linked polymers.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
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 The oldest and still the most popular disintegrants are corn and
potato starch that have been well dried and powdered.
 Starch has a great affinity for water and swells when moistened,
thus facilitating the rapture of the tablet matrix.

 However, others have suggested that its disintegrating action in

tablets is due to capillary action rather than swelling; the
spherical shape of the starch grains increase the porosity of the
tablet, thus promoting capillary action.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
20
 A group of materials known as “super disintegrants” have
gained popularity as disintegrating agents.

 The name comes from the low levels (2-4%) at which they are
completely effective.

 sodium carboxymethylcellulose), polyvinylpyrolidone, and

sodium starch glycolate represent examples of a cross-linked
cellulose, a cross-linked polymer and a cross-linked starch,
respectively.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
21
 Sodium starch glycolate swells 7-to 12-fold in less than 30 sec.

 Croscaramellose swells 4-to 8-fold in less than 10 sec.

 a large variety of materials have been used and are reported to

be effective as disintegrants
 .e.g. Veegum HV (magnisum aluminum silicate),
methylcellulose, agar, bentonite, cellulose, cation-exchange
resins, algenic acid, guar gum, citrus-pulp.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
22
 Lubricants, antiadherents, and glidants
 Lubricants are intended to reduce the friction during tablet
ejection between the walls of the tablet and the walls of the die
cavity in which the tablet was formed.
 Anti-adherents; are intended to promote flow of tablet
granulation or powder materials by reducing friction between
the particles.
 Glidants: have the purpose of reducing sticking or adhesion of
any of the tablet granulation or powder to the faces of the
punches or to the die wall.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
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 The most widely used lubricants Magnesium and calcium
stearate are the most common salts employed.

 Talc is the second most widely used tablet lubricant, historically.

 Most talc samples are found to contain trace quantities of iron,
and talc should be considered carefully in any formulation
containing a drug whose breakdown is catalysed by iron

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
24

 The higher molecular weight polyethylene glycols (e.g.PEG

4000, PEG 6000) and certain surfactants (sodium lauryl sulphate,
sodium stearyl fumarate) and liquid paraffin can be also used as
lubricants.
 Most stearate lubricants are used in concentrations below 1%.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
25
 When used alone, talc may require concentrations as high as
5%.

 The method of adding a lubricant to a granulation is important if

the material is to perform its function satisfactorily.

 The lubricant should be divided finely by passing it through a

60- to 100- mesh nylon cloth onto the granulation.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
26
 After adding the lubricant, the granulation is tumbled or mixed
gently to distribute the lubricant without coating the particles
too well.

 Talc, magnesium stearate, and cornstarch as well as starch

derivatives possess anti adherent properties.

 Colloidal silicon dioxide( Cab-O-Sil) 1% or less, Talc ( at a 5%

conc.), and corn starch at a 5 to 10% conc. are glidants.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
27
 Coloring Agents
 Colors in compressed tablets serve functions other than making
the dosage form more esthetic in appearance.
 Colors help the manufacturer to control the product during its
preparation, as well as serving as a means of identification to
the user.

 Two forms of color have typically been used in tablet

preparation. These are the FD&C and D&C dyes.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
28

 The most common method of adding color to a tablet

formulation is to dissolve the dye in the binding solution prior
to the granulation process.
 Iron oxide, natural pigment

 Another approach is to adsorb the dye on starch or calcium

sulfate from its aqueous solution; the resulting powder is dried
and blended with other ingredients.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
29
 Frequently during drying, colors in wet granulation migrate,
resulting in an uneven distribution of color in the granulation.

 Migration of colors may be reduced by drying the granulation slowly

at low temperature and stirring the granulation while it is drying.

 Other additives have been shown to act as dye migration inhibitors.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
30
 Tragacanth (1%), acacia(3%), attapulgite (5%), and talc (7%) have
been found to be effective in inhibiting the migration.

 Flavoring agents
 Flavors are usually limited to chewable tablets or other tablets
intended to dissolve in the mouth.

 In general, flavors that are water-soluble have found little

acceptance in tablet making because of their poor stability.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
31
 Flavor oils are added to tablet granulations in solvents, are
dispersed on clays and other absorbents, or are emulsified in
aqueous granulating agents.

 Various dry flavors for use in pharmaceutical products are also

available from flavor suppliers.

 Usually the maximum amount of oil that can be added to a

granulation without influencing its tableting characteristic is 0.5
to 0.75%.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
32
 Sweeteners
 In addition to the sweetness that may be afforded by the diluents
of the chewable tablet,
 e.g., mannitol or lactose, artificial sweetening agents may be

used.

 Mannitol is reported to be 72% as sweet as sucrose.

 Until recently, saccharin was the artificial sweetener available.

By Desta T. 06/27/2025
 Tablet Ingredients………..cont’d
33
 This material is about 500 times sweeter than sucrose.

 Its major disadvantage is that it has a bitter after taste and has
been reported to be caricinogenic.

 A new artificial sweetener that is expected to largely replace

saccharin is aspartame.

 The primary disadvantage of aspartame is its lack of stability in

the presence of moisture.

By Desta T. 06/27/2025
 Tablet of types
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There are different types tablet:

 Sugar Coated Tablets (SCT):

 These are compressed tablets surrounded by a sugar coating.
 Such coatings may be colored and are benefice in covering
drug substances possessing objectionable tests or odor and in
protecting materials sensitive to oxidation.

By Desta T. 06/27/2025
 Tablet types….cont’d
35

 Film-Coated Tablets (FCT):

 These are compressed tablets that are covered with a thin
layer or film of a water-soluble material.
 A number of polymeric substances with film-forming
properties may be used.
 Film coating imparts the same general characteristics as
sugar coating with the added advantage of a greatly reduced
time period required for the coating operation.
 Advances in material science and polymer chemistry has
made these coatings the first-choice of formulators.
By Desta T. 06/27/2025
 Tablet types….cont’d
36
 Enteric-Coated Tablets (ECT):
 These are compressed tablets coated with substances that
resist solution in gastric fluid but disintegrate in the intestine.

 Enteric coatings can be used for tablets containing drug

substances that are inactivated or destroyed in the stomach, for
those that irritate the mucosa, or as a means of delayed release
of the medication.


By Desta T. 06/27/2025
 Tablet types….cont’d
37
 Multiple Compressed Tablets (MCT)
 These are compressed tablets made by more than one
compression cycle.
 This process is best used when separation of active ingredients
is needed for stability purposes, or if the mixing process is
inadequate to guarantee uniform distribution of two or more
active ingredients.

By Desta T. 06/27/2025
 Tablet types….cont’d
38

 Layered Tablets:
 Such tablets are prepared by compressing additional tablet
granulation on a previously compressed granulation.
 The operation may be repeated to produce multilayered tablets
of two or three, or more layers.
 Special tablet presses are required to make layered tablets
such as the Versa press(Stokes/Pennwalt)

By Desta T. 06/27/2025
 Tablet types….cont’d
39
 Controlled-Release Tablets (CRT)
 Compressed tablets can be formulated to release drug slowly over
prolonged period of time.
 Tablets for Solution(CTS):
 Compressed tablets to be used for preparing solutions or imparting
given characteristics to solution must be labeled to indicate that
they are not to be swallowed.
 Examples of these tablets are Halazone Tablets for Solution and
Potassium Permanganate Tablets for Solution.

By Desta T. 06/27/2025
 Tablet types….cont’d
40

 Effervescent Tablet:
 In addition to the drug substance, these contain sodium
bicarbonate and an organic acid such as tartaric or citric.
 In the presence of water this additives react, librating carbon
dioxide.
 Buccal and Sublingual Tablets:
 These are small, flat, oval tablets.

 Tablets intended for buccal administration by inserting into

the buccal pouch may dissolve or erode slowly; therefore,

they are formulated and compressed with sufficient
pressure to give a hard tablet.
By Desta T. 06/27/2025
 Tablet types….cont’d
41

 Molded Tablets or Tablet Triturates(TT):

 Tablet triturates usually are made from moist material,

using a triturate mold that gives them the shape of cut

sections of a cylinder
 Such tablets must be completely and rapidly soluble.
 The problem arising from compression of these tablets is the
failure to find a lubricant that is completely water-soluble

By Desta T. 06/27/2025
 Tablet types….cont’d
42
 These tablets are supplied primarily as a convenience for
extemporaneous compounding and should never be
dispensed as a dosage form.

 Hypodermic Tablets (HT):

 Hypodermic tablets are soft, readily soluble tablets and

originally were used for the preparation of solutions to be

injected.
 Since stable parentral solutions are now available for most

drug substances, there is no justification for the use of

hypodermic tablets for injection.

By Desta T. 06/27/2025
 Tablet types….cont’d
43

 Their use in this manner should be discouraged, since the

resulting solutions are not sterile.
 Large quantities of these tablets continue to be made, but for
administration.
 No hypodermic tablets ever have been recognized by the
official compendia.

By Desta T. 06/27/2025
 Tablet types….cont’d
44

 Compressed Suppositories or Inserts

 Occasionally, vaginal suppositories, such as Metronidazole
tablets, are prepared by compression.

 Tablets for this use usually contain lactose as diluent.

 In this case, as well as for any tablet intended for
administration other than by swallowing , the label must
indicate the manner in which it is to be used.

By Desta T. 06/27/2025
 Fundamentals of powder
compaction
45
 Compactibility may be defined as the ability of a powder to
form a coherent tablet as a result of compression.

 The compressibility is defined as the ability of a powder to

decrease in volume under pressure.
 A powder with a high compactibility forms tablets with a
high resistance towards fracturing and without tendencies to
cap or laminate.
 The process of compaction has several identifiable phases.

By Desta T. 06/27/2025
 Fundamentals of powder
compaction……cont’d
46

 Consolidation phase
 When powders undergo compression, the first process to

occur is a consolidation of the powders.

 During this phase the powder particles adopt a more

efficient packing order.

 Elastic or reversible deformation
 If the force were removed during this phase, the powder

would recover completely to the efficiently packed state.

 For most pharmaceutical powders, this phase is very short

in duration and very difficult to identify on most

instrumented tablet presses.
By Desta T. 06/27/2025
 Fundamentals of powder
compaction……cont’d
47

 Plastic or irreversible deformation

 This is the most critical phase in tablet formation

 Brittle fracture
 If too much force is applied to the powder, brittle fracture

occurs.
 If the force was applied too quickly, fracture and de-bonding

can occur during stress relaxation.

By Desta T. 06/27/2025
 Fundamentals of powder
compaction……cont’d
48

By Desta T. 06/27/2025
 Mechanism of tablet
manufacturing
49
 Compressed tablets may be made by three basic methods: wet
granulation, dry granulation, and direct compression.

 One important requirement in tablet manufacture is that the drug

mixture flow freely from the hopper of tablet press into the dies
to enable high-speed compression of the powder into tablets.

 Granulation of powder provide this free flow, increases

material density, and improve powder compaction.

By Desta T. 06/27/2025
 Tablet manufacturing…………..cont’d
50
 Wet granulation
 Wet granulation is widely used method for production of
compressed tablets.
 The steps required are:
 Weighing of drug and excipients

 Milling (if necessary)

 Screening of drug and excipients (if necessary)

 Mixing of milled powders (API, diluent, disintegrant)

 Preparation of binder solution

 Preparation of wet mass

By Desta T. 06/27/2025
 Tablet manufacturing…………..cont’d
51
 Granulating of wet mass using 6- to 12-
mesh (granulator dependent)
 Drying moist granules

 Milling and screening dry granules

 Mixing the screened granules with, lubricant,

antiadherent, and glidant

 Tablet compression

By Desta T. 06/27/2025
 Tablet manufacturing…………..cont’d
52

 Care must be exercised not to over wet or under wet the

powder.

 Under wetting (over drying) can result in granules that are too
hard where as;
 Over wetting (under drying))can results in tablets that are too
soft.

By Desta T. 06/27/2025
 Tablet production process by
wet granulation method
53

By Desta T. 06/27/2025
 Tablet manufacture by dry
granulation method
54
 Dry granulation
 By the dry granulation method, the powder mixture is compacted
in large pieces and subsequently broken down or sized into
granules.

 For this method, either the active ingredient or the diluent must
have cohesive properties.

 There are two method of dry granulation. These are slugging and
roller compaction.

By Desta T. 06/27/2025
 Tablet manufacture by dry
granulation method
55
 Slugging
 After weighing and mixing the ingredients, the powder mixture is
slugged, or compressed into large flat tablets or pellets about 1 inch
in diameter.

 The slugs are broken by hand or by a mill and passed through a

screen desired mesh or sizing.

 Lubricant, antiadherent, and glidant are added in the usual manner,

and tablet are prepared by compression.

By Desta T. 06/27/2025
 Tablet manufacture by dry
granulation method
56
 Roller compaction
 Instead of slugging, powder compactors may be used to increase
the density of the powder by pressing it between rollers at a 1 ton
to 6 ton of pressure.

 The compacted material is broken up, sized and lubricated, and

tablets are prepared by compression in the usual manner.

By Desta T. 06/27/2025
 Tablet production process by
dry granulation method
57

By Desta T. 06/27/2025
 Tablet manufacture by direct
compression method
58

 Direct compression
 The term direct compression is now used to define the process
by which tablets are compressed directly from powder blends of
the active ingredient and suitable excipients (including fillers,
disintegrants, and lubricants), which will flow uniformly into a
die cavity and form into a firm compact.

 No pretreatment of the powder blends by wet or dry granulation

procedures is necessary.

By Desta T. 06/27/2025
 Tablet manufacture by direct
59
compression method
 There are a few crystalline substances, such as sodium chloride,
sodium bromide, and potassium salts( chlorate, chloride,
bromide, iodide, nitrate, permenganate), ammonium chloride and
methenamine, that may be compressed directly.
 These materials less cohesive and flow properties that make
direct compression possible.
 For tablets in which the drug itself constitutes a major portion of
the total tablet weight, it is necessary that the drug possess those
physical characteristics required for the formulation to be
compressed directly.

By Desta T. 06/27/2025
 Tablet manufacture by direct
compression method
60
 Direct compression for tablets containing 25% or less of drug
substance frequently can be used by formulating with a suitable
diluent as carrier or vehicle for the drug.

 Direct-compression vehicles or carriers must have good flow or

compressible characteristics.

 Direct compression has some important advantages such as low

labor input, a dry process, and fewest processing steps.

By Desta T. 06/27/2025
 Tablet manufacture by direct
compression method
61

 These vehicles include processed forms of most of the common

diluents including

 dicalcium phosphate dihydrate, tricalcium phosphate, calcium sulfate,

anhydrous lactose, spray-dried lactose, pregelatinized starch, mannitol,
and microcrystalline cellulose (Avecel).

By Desta T. 06/27/2025
 Tablet production process by
62
direct compression method

By Desta T. 06/27/2025
 Tablet manufacturing
63
 Stages in tablet formation
 Tablets are prepared by forcing particles into close proximity to
each other by powder compression.
 The compression takes place in a die by the action of two
punches, the lower and the upper, by which the compressive
force is applied.
 The process of tabletting can be divided into three stages
(sometimes known as the compaction cycle).
 These are: Die filling, tablet formation, and tablet ejection

By Desta T. 06/27/2025
 Tablet manufacturing………………..cont’d
64
 Die filling: This is normally accomplished by gravitational
flow of the powder from a hopper via the die table into the
die.
 The die is closed in its lower end by the lower punch.
 Tablet formation:
 The upper punch descends and enters the die and the powder
is compressed until a tablet is formed.
 During the compression phase, the lower punch can be
stationary or can move upwards in the die.

By Desta T. 06/27/2025
 Tablet
manufacturing………………..cont’d
65
 After maximum applied force is reached, the upper punch leaves
the powder, i.e. the decompression phase.
 Tablet ejection
 During this phase the lower punch rises until its tip reaches the
level of the top of the die.
 The tablet is subsequently removed from the die and die table by a
pushing device.

By Desta T. 06/27/2025
 Tablet presses
66
 There are two types of presses in common use during
tablet production: the single-punch press and the
rotary press.
 Single-punch press (eccentric press)
 A single-punch press possesses one die and one pair of
punches.
 The powder is held in a hopper which is connected to a hopper
shoe located at the die table.
 The hopper shoe moves to and fro over the die, by either a
rotational or a translational movement.

By Desta T. 06/27/2025
 Single-punch press
67

By Desta T. 06/27/2025
 Single-punch press
68

By Desta T. 06/27/2025
69

By Desta T. 06/27/2025
 Tablet presses….Cont’d
70
 When the hopper shoe is located over the die, the powder is
fed into the die by gravity.
 The amount of powder filled into the die is controlled by the
position of the lower punch.
 When the hopper shoe is located beside the die, the upper
punch descends and the powder is compressed.
 The lower punch is stationary during compression and the
pressure is thus applied by the upper punch and controlled by
the upper punch displacement.

By Desta T. 06/27/2025
 Tablet presses….Cont’d
71
 After ejection the tablet is pushed away by the hopper shoe as
it moves back to the die for the next tablet.
 The output of tablets from single punch press is about 200
tablets per minute.

 A single-punch press thus has its primary use in the

production of small batches of tablets, such as during
formulation development, and during small scale
production, such as production for clinical trials.

By Desta T. 06/27/2025
 Rotary press
72
 The rotary press (also referred as multi-station press) was
developed to increase the output of tablets.
 The primary use of this machine is thus during scale-up in the
latter part of formulation work, and during large scale production.
 Outputs of over 10,000 tablets per minute can be achieved by
rotary presses.
 Rotary press operates with a number of dies and sets of punches,
which can considerably from 3 for small presses up to 60 or more
for large presses.

By Desta T. 06/27/2025
 Rotary press machine

73

By Desta T. 06/27/2025
 Rotary press…..Cont’d
74
 The dies are mounted in a circle in the die table and both the
die table and the punches rotate together during operation of
the machine, so that one die is always associated with one
pair of punches.
 The vertical movement of the punches is controlled by cam
tracks.
 There are rolls used to control the volume of powder fed into
the die and apply pressure for compression.
 The powder is held in a hopper whose lower opening is
located just above the die table.

By Desta T. 06/27/2025
 Rotary press…..Cont’d
75
 The powder flows by gravity on to the die table and is fed into
the die by a feed frame.
 The reproducibility of the die feeding can be improved by a
rotating device referred to as a force-feeding device.

By Desta T. 06/27/2025
76

By Desta T. 06/27/2025
77

Tablet Quality Control Test

By Desta T. 06/27/2025
Quality control test for Tablet…

 Thickness and diameter

 Weight variation
 Hardness
 Friability
 Drug content
 Disintegration time
 In- vitro dissolution
Quality control test for Tablet…

General Appearance:
-Size, shape, and thickness:
This is important to facilitate packaging and to
decide which tablet compressing machine to
use.
-Organoleptic properties:
which include color, taste and odor of the
tablets.
Quality control test for Tablet…
⦿ Thickness can vary with no change in
weight

due to:

a.Difference in the density of the

granulation

b. The pressure applied to the tablets.

c. The speed of tablet compression.

 Quality control test for Tablet…
81

 Compressed tablets may be characterized by a number of

specifications.
 The diameter and shape depend on the die and the punches
selected for the compression of the tablet.
 Generally, tablets are discoid in shape, although they may be oval,
oblong, round, cylindrical, or triangular.

By Desta T. 06/27/2025
 Quality control test for Tablet…
82

Tablet shapes

By Desta T. 06/27/2025
 Quality control test for Tablet…
83
 The top or lower surface of a tablet may be embossed or
engraved with a symbol or letters that serve as an additional
means of identifying the source of the tablets.
 The remaining specifications assure the manufacturer that the
tablets do not vary from one production lot to another.
 In the case of new tablet formulations their therapeutic efficacy is
demonstrated through clinical trials, and it is the manufacturer’s
aim to reproduce the same tablet with the exact characteristics of
the tablets that were used in the clinical evaluation of the dosage
form.

By Desta T. 06/27/2025
 Quality control test for Tablet…
⦿ Tablet thickness: important in reproducing
tablets identical in appearance but also to
insure that every production lot will be usable
with selected packaging components.
⦿ Tablet thickness is determined with a caliper or
thickness gauge that measures thickness in
millimeter.

⦿ If the tablets are thicker than specified, a given

number no longer may be contained in the volume
of a given size bottle.
⦿ A plus or minus 5% may be allowed,
depending on the size of
the tablet.
Cliper
 Quality control test for Tablet…

 Hardness (crushing strength):

It is the load required to crush the tablet
when placed on its edge.
Why do we measure hardness?
⦿ To determine the need for pressure adjustments on the
tableting machine.
⦿ To withstand the mechanical shocks of
manufacturing, packaging, and shipping,
⦿ To ensure consumer acceptance.
Quality control test for Tablet…
⦿ Hardness can affect the disintegration. So if the tablet
is too hard, it may not disintegrate in the required period
of time. And if the tablet is too soft, it will not withstand
the handling during subsequent processing such as
coating or packaging.

>In general, if the tablet hardness is too high, we first

check its disintegration before rejecting the patch. And
if the disintegration is within limit, we accept the patch.

Monsanto or Stokes hardness tester

Quality control test for Tablet…
Factors Affecting the Hardness:
⦿ Compression of the tablet and compressive force.
⦿ Amount of binder. (More binder à more hardness)
⦿ Method of granulation in preparing the tablet
(wet method gives more hardness than direct
method, Slugging method gives the best
hardness).

⦿Limits:
 Oral tablets have a hardness of 4 to 10kg ;
 Or dispersible and chewable tablets
hardness of 3kg
>Make hardness release
 sustained test on 5 tablets
tablets and about
have then take
10-20
thekg.
average hardness.
Quality control test for Tablet…

 Friability:
 It is the tendency of tablets to powder,
chip, or fragment and this can affect the
elegance appearance, consumer
acceptance of the tablet, and also add to
tablet’s weight variation or content
uniformity problems.
 Friability is a property that is related to the
hardness of the tablet.
 An instrument called friabilator is used to
evaluate the ability of the tablet to
Quality control test for Tablet…
 Friabilator determine friability by allowing the
tablet to roll and fall 6 inches within a
rotating tumbling apparatus.

Roche friabilator.
 Quality control test for
Procedure: Tablet…
1. Weigh 20 tab altogether
2. Put these tablets in the friabilator and adjust the
instrument at 100 rpm (i.e. = 25 rpm for 4 min)

3. Weigh the 20 tablets (only the intact ones)

F = 100 × (1-w/w0)
Where w0 = weight of tablets before friability
w = weight of tablets after
friability
4. Friability (% loss) = It must be less than or equal to1% but

 Some chewable tablets and most effervescent tablets are

highly friable and require special unit packaging.
 Quality control test for Tablet…
 Weight Variation (uniformity of weight) of tablets
:
 The weight variation test would be a satisfactory method
for determining drug content uniformity of drug
distribution.
 Weight variation test is applicable when the tablets
containing 50 mg or more of drug substance or when the
drug substance represents 50% or more (by weight) of the
dosage form unit.

1. Weigh 20 tablet selected at random, each one individually . X1,

X2, X3… Xz
2. Determine the average weight. X= (X1+X2 +X3+…+
Xz)/20
Quality control test for Tablet…
Limits according to
U.S.P
 Quality control test for Tablet…
⦿ Limit:
⦿ Upper limit = average weight + (average
weight * %error)
⦿ Lower limit = average weight - (average
weight * %error)
⦿ The individual weights are compared with
the upper and lower limits.
>>Not more than two of the tablets differ from
the average weight by more than the % error
listed, and no tablet differs by more than
double that percentage.
Tablets that are coated are exempt from
these requirements but must conform to
Quality control test for Tablet…

 Content Uniformity Test:

 Randomly select 30 tablets then 10 of these
assayed individually.
 The Tablet pass the test if 9 of the 10 tablets must
contain not less than 85% and not more than
115% of the labeled drug content and the 10th
tablet may not contain less than 75% and more
than 125% of the labeled content.
 If these conditions are not met, remaining 20
tablet assayed individually and none may fall out
side of the 85 to 115% range.
 Nine of 10 must contain labeled amount ± 15%
and none exceed ± 25% .
Quality control test for Tablet…
 Disintegration:
 It is the time required for the tablet to
break into particles, the disintegration
test is a measure only of the time
required under a given set of
conditions for a group of tablets to
disintegrate into particles which will
pass through 10 mesh screen. .
 Quality control test for Tablet…
 The Disintegration apparatus consists of a basket
rack holding six plastic tubes, open at the top
and bottom; the bottom of the tubes is covered with
10-mesh screen
 The basket rack is immersed in a bath of suitable
liquid, held at 37°, preferably in a 1 -L beaker. The
rack moves up and down in the fluid at a specified
rate.
 For compressed uncoated tablets the testing
fluid is usually water at 37°, but in some cases
the monographs direct that simulated gastric
fluid be used.
Quality control test for Tablet…
 Liquids used in disintegration
⦿ Water,
⦿ simulated gastric fluid (PH =1.2 HCl),
⦿ or Simulated intestinal fluid
Quality control test for Tablet…
 For most uncoated tablets the period is not
more than 30 minutes according to USP
( to Bp 15 minutes), although the time for some
uncoated tablets varies greatly, from this.
 For coated tablets up to 2 hours may be
required,
 while for sublingual tablets, the
disintegration time is 3 minutes.

 The tablet disintegration test is limited to

manufacturing control of lot-to-lot variations
in individual products and is not a measure of
bioavailability.
 It is used to provide a simple and useful means
for monitoring and controlling the quality of
 Quality control test for Tablet…
U.S.P. method for uncoated tablets:
 Start the disintegration test on 6 tablets.
 If one or two tablets from the 6 tablets fail
disintegrate completely within 30min
repeat the same test on another 12
tablet. (i.e. the whole test will consume 18
tablets).
 Not less than 16 tablets disintegrate completely
within the time
 if more then two tablets (from the 18) fail to
disintegrate, the batch must be rejected.
 Quality control test for Tablet…
Medium Temperature Time
limit

According Simulated 37oC Not

to U.S.P. gastric fluid exceed
30min

According water 37oC Not

to B.P. exceed
15min

10 By Desta T. 06/27/2025
0
 Quality control test for Tablet…
 Dissolution test
• Dissolution is the process by which a solid enters
a solution .
• The dissolution rate is defined as the amount
of drug substance that goes into solution per
time under standardized conditions of liquid / solid
interface, temperature, and solvent composition .

• Dissolution is one of most important quality

control tests and consider as tool for
predicating bioavailability , in some cases,
replacing clinical studies to determine
bioequivalence.
 Quality control test for Tablet…
 A variety of designs of apparatus for
dissolution testing is varying from simple
beaker to complex system where an
attempt is made to mimic the biological
media.

The choice of the apparatus to be used

depends largely on the physicochemical properties
of the dosage form.
Quality control test for Tablet…

Apparatusa Name Drug Product

Apparatus 1 Rotating basket Tablets

Apparatus 2 Paddle Tablets, capsules, modified drug products, suspensions
Apparatus 3 Reciprocating cylinder Extended-release drug products
Apparatus 4 Flow cell Drug products containing low-water-soluble drugs
Apparatus 5 Paddle over disk Transdermal drug products
Apparatus 6 Cylinder Transdermal drug products
Apparatus 7 Reciprocating disk Transdermal drug products
Rotating bottle (Non-USP-NF) Extended-release drug products (beads)
Diffusion cell (Franz) (Non-USP-NF) Ointments, creams, transdermal drug products

Apparatus 1–7 refer to compendial dissolution apparatus in USP-NF (United States

a

Pharmacopeia)
24
Quality control test for Tablet…

2
Quality control test for Tablet…
 All 6 tablets must meet the requirements specific.

 If one or two tablets failed, repeat the test on 6

additional tablets

 In most cases the amount of drug dissolved

should:

 not be less than 70% of quantity contained

in tablet after 45min.

3
 Quality control test for Tablet…

• Various pharmacopoeias contain specifications on dissolution

requirements of various drugs. ( monograph specifies :
stirring speed, temperature, viscosity, pH, composition
of dissolution media and presence or absence of wetting
agent)
 Tableting problems
10
7
 Tableting imperfections may happen in any one or more of the
following factors:
 Capping

 Lamination / Laminating

 Chipping

 Sticking / Filming

 Picking

 Mottling etc…

By Desta T. 06/27/2025
10
8

Lecture: 3

Tablet Coating

By Desta T. 06/27/2025
10
9 What are the rationales for tablet coating?

1. To protect the drug from the environment

2. Masking of unpleasant testes
3. Making it easier to swallow
4. Improve product identity
5. Facilitate handling as it removes dust

By Desta T. 06/27/2025
11
0

6 Improves product appearance when there is noticeable

difference between batches
7 Reducing the risk of interaction between incompatible
components
8 Increase product robustness as coated products generally are
more resistant to mis - handling e.g. Abrasion and attrition
9 Modifying drug release

By Desta T. 06/27/2025
 Types of coating processes
11
1

 Basically there are four major techniques for applying

coatings to pharmaceutical dosage forms
1. Film coating
2. Sugar coating
3. Compressed coating
4. Gelatin coating

By Desta T. 06/27/2025
 Filma Coating
11
2  Film coatings add very little extra weight (up to approx.
5% increase)
 Various polymers (e.g. cellulose derivatives like HPMC)
are used in film coating
 Ideal film polymers have
- good solubility
- low viscosity
- low permeability to water vapor
- high mechanical strength

By Desta T. 06/27/2025
11
3

 The basic components of the coating formulation:

- Film Former
- Solvent
- Plasticizer
- Colorant
- Opacifiers
- Miscellaneous - flavors, sweeteners, surfactants,
antioxidants, antimicrobials

By Desta T. 06/27/2025
 The coating Process
11
4  Film Formation
 Think of the polymers used in film coating as flexible
strands
 When they are in liquid form, they move easily in and
amongst other polymer chains
 When cooled to solidify the film, the polymer chains come
in contact with each other and become entangled, sticking
together

By Desta T. 06/27/2025
11
5 
The function of plasticizers is to get in the way of these tight
interactions to make the film more flexible so it doesn’t crack

 (Prevents a more crystalline type of film from forming) In

polymer chemistry, this is called "doping" i.e. deliberately
adding a contaminant to the pure polymer to change its
physical properties, such as melting point.

By Desta T. 06/27/2025
11
6
 Types of film coating:
1) Immediate-release (non-functional) film coating:
 They do not affect the biopharmaceutical properties of the

tablet
 They are readily soluble in water

2) Modified-release (functional) film coating:

 They allow the drug to be delivered in a specific manner;
i.e. they affect drug release behavior
 Modified release film coatings are sub-classified into;
 Delayed-release coating (enteric coating)
 Extended-release coating

By Desta T. 06/27/2025
11
7
Problems:
- Product erosion

- Product instability due to unacceptable high latent moisture

- Mixing of tablet mass:

By Desta T. 06/27/2025
 Sugar Coating
11
8

- It relies primarily on the use of sucrose

- Sucrose produces: Smooth, Dry and Tack free

 Sugar coating is the oldest method of tablet coating

 It is also the most complex, expensive, requires great
expertise – nearly an art, it is time-consuming, and it
increases the tablet weight significantly

By Desta T. 06/27/2025
 Step of sugar coating
.
11
9  1. sealing stage uses shellac or cellulose
acetate phthalate, for example, to prevent
moisture from reaching the tablet core.
 2. subcoating is an adhesive coat of gum
(such as acacia or gelatin) and sucrose
used to round off the edges, and the
tablets can be dusted with substances
such as kaolin or calcium carbonate to
harden the coating.

By Desta T. 06/27/2025
 Step of sugar coating
12
0

3. A smoothing coat is built up in

layers using 70% v/v sucrose syrup
and often opacifiers such as
titanium dioxide, and the tablets are
dried between each application.
4. A colorant

By Desta T. 06/27/2025
12
1
 Materials used in the sugar coating process include purified
water, cellulose derivatives, polyvinyl, gums, and sugar
 The advantage of sugar coating is the very smooth, high-
quality surface it provides to the tablets (observe the coating
of a chocolate piece), which is dry and not tacky ("melts in
your mouth, not in your hand")
 If well-made, these are examples of tablets with
"pharmaceutical elegance."

By Desta T. 06/27/2025
 Compression Coating/Press Coating
12
2
 Compaction of a dry coat around a tablet core, produced on
the same tableting machine
 This type of coating avoids the use of solvents
 It can be used to separate incompatible drugs in the same
tablet, making a layered tablet. (eg. Robaxisal®)
 Machinery for tableting this way is complex and not widely
used.

By Desta T. 06/27/2025
12
3

 Mechanically, it is a complex process, as the tablet may be

tilted when transferred to the second die cavity.

 Mostly, the coat is water-soluble and disintegrates easily after

swallowing, in order to achieve immediate-release product}.

By Desta T. 06/27/2025
 Gelatin-coated tablets

12
4

 The innovator product, the gelcap, is a capsule shaped

compressed tablet coated with gelatin layer.

By Desta T. 06/27/2025
12
5

By Desta T. 06/27/2025
12
6

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By Desta T. 06/27/2025