tablet manufacturing process.pptx

Oral dosage form
Module-1
Tablets Dosage Form manufacturing
Prepared by: Surafel Kebede(Bpharm,MBA)
safokebede@gmail.com
2

Table of contents
1. Dosage forms
2. Tablet dosage forms
3. Desirable properties of tablets
4. Classification of tablets
5. Types of tablets
6. Tablet ingredients
7. Tablet manufacturing methods
8. Major equipments used for wet granulation
9. Evaluation of tablets
10.Tableting problems and their remedies
3

After completing this training, trainees should be able to:
Define dosage form and understand their
classification.
Define tablet dosage form, desirable properties, and
types of tablets.
Describe the function of each ingredients used in
tablet dosage form formulation.
Explain tablet manufacturing methods widely used.
Explain how tablets are evaluated.
 explain tablet problems and their remedies.
objectives
4

1. Dosage Forms
5
 Dosage forms are the means by which drug
molecules/APIs are delivered to sites of action within
the body to produce optimum desired effects and
minimum adverse effect.
 Dosage forms are pharmaceutical drug products in
the form in which they are marketed for use, with a
specific mixture of active ingredients and inactive
components (excipients), in a particular configuration
(such as a capsule shell, for example), and
apportioned into a particular dose.

Dosage Forms of drugs
6
Dosage forms are the means by which drug
molecules/APIs are delivered to sites of
action within the body to produce optimum
desired effects and minimum adverse effect.

1.1. Oral solid Dosage Forms
7
Oral solid dosage forms are types of solid
dosage forms that are administered orally.
Tablet is one kind of oral solid dosage form.

Definition:
 Tablets: are pharmaceutical solid unit dosage
forms containing drug substances with or
without diluents and prepared by either
compression or molding methods.
 Tablets may be defined as the solid unit dosage
form of medicament or medicaments with
suitable excipients.
2. Tablet Dosage Forms
8

 tablets are the most popular dosage forms
today.
 About two-thirds of all prescriptions are
dispensed as solid dosage forms, and half of
these are compressed tablets.
 Tablets can exist in different shape, size and
weight; which depend upon amount of drug
used and mode of administration.

Tablet…
9

Tablet...
10
Tablets-wide shape range

Palatability/ease of administration
Portability
Easier to manufacture
Accurate dosing
Stability
Easier to pack, ship & store
Why Tablets?
11

Must be elegant in appearance and must have
characteristic shape, colour, and other markings
necessary to identify the product.
Must be sufficiently strong, resistance to shock and
abrasion. Withstand handling during manufacturing,
packing, shipping and use.
Must be uniform in weight and drug content.
The drug content of the tablet must be bioavailable.
Must be stable, effective and safe.
3. Desirable properties of Tablets
12

4. Classification of Tablets
 They may be classed, according to the method of
manufacture, as compressed or molded tablets.
 Tablets are prepared primarily by compression of
granules or powder blends, with a limited
number prepared by molding.
13
molded tablets

5. Types of tablets
Tablets are classified according to their route of
administration or function. The following are the
four main classification groups:
I. Tablets ingested/swallowed orally
1.Compressed tablets
Are made by either direct compression, wet
granulation or dry granulation, in their simplest
form, no special coating.
The vast majority of tablets commercialized today
are compressed tablets.
Eg, paracetamol, aspirin
14

Types…
2. Multiple compressed tablets
Are 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 or to
produce repeat action or prolonged action products.
15

Types…
 Layered tablets: are tablets prepared by compressing
additional tablet granulation on a previously compressed
tablet. This operation is repeated a number of times to
produce a multi-layered tablet. Special tablet presses are
required to make layered tablets such as versa press.
16
Layered tablets
Triple Layer Tablet Press

Types…
3. Controlled-release tablets
Compressed tablets can be formulated to
release the drug slowly over a prolonged period
of time.
17

Types…
18
4.Coated tablet
 sugar-coated: are compressed tablets
surrounded by a sugar coating. Such coatings
used to cover up taste and odor and protect
actives sensitive to oxidation.

Types…
 film-coated: the compressed tablets can
be coated with some polymer substance
and used to protect the API from light
and taste masking.
19

Types…
Enteric-coated: these are tablets that are coated with
polymer that does not dissolve under acidic
conditions (i.e stomach up to pH 4) but does dissolve
under the more alkaline conditions of the small
intestine (pH range 7-8).
20

Types…
5. Chewable tablets
 These tablets are required to be broken and chewed in
between the teeth before ingestion.
 These are given to children and elderly peoples.
 contain flavorants and sweeteners (mannitol, sorbitol,
sucrose etc)..
 Antacid tablets, vitamin C are examples of chewable tablets.
21

Classification of ….
II Tablets used in the oral cavity:
1) Sublingual tablet: placing under the tongue.
 rapidly dissolve in mouth and absorbed through the
mucous membrane of mouth.
 Drug reaches in systemic circulation without affecting by
gastric juices and metabolizing enzymes of the liver.
 Examples; Vasodilators, Steroidal hormones.
22

2) Buccal tablets: placing into Buccal pouch
(between the gum and the cheek).
These tablets should nod disintegrate rapidly
in the mouth rather they should dissolve slowly
for 15-30 minutes for absorption from the oral
mucosa.
23

3 Lozenge &Troches: Used in the oral cavity to exert local
effect in mouth and throat.
The tablets are dissolving slowly over a period of 30
minutes.
Lozenges usually formed by fusion or by a candy
molding process, troches are manufactured by compression
methods.
Generally contain a sweetening and flavoring agent.
24

4. Dental Cones:These tablets are designed to be
loosely pack in the empty socket remaining following a
tooth extraction.
Used for preventing the local multiplication of
pathogenic bacteria associated with tooth
extractions.
Formulated to dissolve or erode slowly in presence of
a small volume of serum or fluid over 20-40 minutes
period.
25

III Tablets for administration in other Sites:
1) Implantable tablet:These tablets are inserted into
subcutaneous tissue by surgical procedures where they are
very slowly absorbed over a period of a month or a year.
These methods require special surgical technique for
implantation and discontinuation of therapy. Generally
used for administration of contraceptives.
26

2) Vaginal tablet:These tablets are meant to
dissolve slowly in the vaginal cavity.
used as antibacterial, and antiseptic to treat
vaginal infection.
27

Classification of Tablets
IV. Tablets used to prepare solutions
1.Effervescent tablet: is intended to be dissolved or
dispersed in water before use,
is uncoated and generally contains acid
substances (citric and tartaric acids) and
carbonates or bicarbonates , which react rapidly
in presence of water and release carbon dioxide.
28

Classification…
2.Dispensing tablet:These tablets also referred to as compounding
tablets.
 They contain large amount of highly potent APIs and thus are used
by pharmacists to compound prescriptions that can be
incorporated readily into powders and liquids.
 Dispensing tablets are no longer in use and had the dangerous to
dispense inaccurately.
29

Classification…
3. Hypodermic tablets:These tablets contain one or
more soluble ingredients and are intended to be
added in water for injection or sterile water to
form a clear solution which is to be injected
parenterally.
It can be used for medicaments whose stability in
water is very poor.
These tablets are no longer in use because of
contamination issues.
30

Classification…
4. Tablet triturates:These are powders molded into
tablets.
 They are flat, circular discs, usually containing a
potent substance mixed with lactose, lactose and
sucrose, dextrose or other suitable diluents.
 Such tablets must be completely and rapidly soluble.
31

Tablets provide an accurate, stable dose with
greatest precision and least content variability.
Easy to use, handle and carry by the patient
Attractive and elegant in appearance
The manufacturing cost is low and the
manufacturing speed is also quite high.
32
Advantages of tablet dosage forms

The packaging and shipping of tablets is easy
and cheap
Mask unpleasant taste and odor of medicaments
Fewer incompatibilities and deterioration due to
environmental factors are less in case of tablet
33
Advantages…

 Whenever a fractional dose is required, tablets
are divided into halves and quarters by drawing
lines during manufacturing to facilitate
breakage
 They are more suitable for large scale
production than other oral dosage forms
 Tablets provide administration of even minute
dose of drug in an accurate amount
34
Advantages…

Their identification is probably the easiest
because of variety of shapes and colors.
Tablets are formulated with certain special
release profile products such as enteric or
delayed release products
They are economical as their cost is lowest as
compared to other oral dosage forms
35
Advantages…

Disadvantages
Drugs that are amorphous, hygroscopic in
nature.
Drugs that are difficult to compress into
tablet.
Drugs having poor wetting properties,
slow dissolution profile and poor gastro
intestinal absorption are difficult or
impossible to formulate as a tablet
36

Disadvantages…
Drugs that are sensitive to oxygen or may also
require certain treatment like special coating as
well as packaging which may increase the
overall manufacturing cost.
High dose drugs are difficult to formulate as
tablet dosage form.
Swallowing of tablets especially by children
and critically ill patients is very difficult.
37

6. Tablets Ingredients
Inactive ingredients/excipients are natural or
synthetic substances added together with the
active ingredient.
Many guidelines exist to aid in selection of non
toxic excipients such as;
IIG (Inactive Ingredient Guide),
GRAS (Generally Regarded As Safe),
Handbook of Pharmaceutical Excipients and
others.
38

Ingredients…
 Excipients can also be useful in the manufacturing
process, to aid in the handling of the active
substance.
39

Tablets Ingredients…
While Selection of excipients
 Keep the excipients to a minimum in number
minimize the quantity of each excipients.
 Multifunctional excipients may be given
preference over uni-functional excipients.
 Compatibility profile of them should be known
before use, because excipients may have
interaction.
41

1. Diluents/fillers
Diluents/Fillers are incorporated into the
formulation to increase the size of the tablet so
that the size can be suitable for handling.
Fillers are also used if the dose of drug per tablet
is low and the tablet would otherwise be too
small.
Diluents are often added to tablet formulations:
• to improve cohesion
• to allow direct compression
• to enhance flow
46

Classified on the basis of their solubility
47

2. binders/Adhesives
Binders hold the active and inactive ingredients
in a tablet together.
Binders ensure that tablets and granules can be
formed with required mechanical strength, and
give volume to low active dose tablets
.
48

Binders are usually;
49

concentration of commonly used binder
52

3. Disintigrants
Disintigrants encourage the tablet to break
down into small fragments(granules) when it is
ingested or when placed in an aqueous
environment.
 This promotes the rapid dissolution and
absorption of the drug, enabling it to exert its
therapeutic action more quickly.
53

3. list of super-disintegrants
55

4. Lubricants
 Lubricants ensure that the tableting powder
does not adhere to the die wall of the punches.
 Used to reduce the friction during tablet
formation in a die and also during ejection
from die cavity.
56

5. Antiadherents
used to reduce the adhesion between the
powder (granules) and the punch faces and
thus prevent sticking to tablet punches. Talc,
magnesium stearate and corn starch have
excellent antiadherent properties.
58

6. Glidants
to promote the flow of tablet granules or
powder mixture from hopper to the die cavity
by reducing friction between the particles.
Talc is a glidant which is superior to starch
Silaceous material like colloidal silica i.e.
syloid, pyrogenic silica (0.25%).
60

7. Colorant
 Colors are added to improve the appearance
of a formulation.
 Color consistency is important as it allows
easy identification of a medication
Colorants can be classified into:
1. Water soluble dyes
Used in wet granulation process
2. Water insoluble dyes(Lakes)
Used in direct compression process
61

8. Flavors and sweeteners
Flavors and sweeteners are commonly used to
improve the flavor and taste of chewable tablets.
Flavors are incorporated as solids in the form of
spray-dried beadlets and oils usually at the
lubrication step.
Dry flavors are easier to handle and more stable
than oils.
they can be used to mask unpleasant tasting
active ingredients and improve the acceptance
that the patient will complete a course of
medication.
62

Flavours and sweeteners….
Examples of Sweeteners:
Saccharin is about 400 times sweeter than sucrose
Aspartame is about 180 times sweeter than sucrose.
64

9. Adsorbents
 Adsorbents such as silicon dioxide ( Syloid, Cab-O-Sil,
Aerosil ) are capable of retaining large quantities of
Liquids without becoming wet . This allows many oils,
fluid extracts and eutectic melts to be incorporated into
tablets .
 Also other adsorbents include clays like bentoniter and
kaolin, mag. Silicate, tricalciun phosphate, magnesium
Carbonate, and magnesium Oxide.
65

10. Wetting agents
to aid water uptake during disintegration and
assist drug dissolution.
11. Dissolution retardants
retards the dissolution of active pharmaceutical
ingredient(s).
12. Dissolution enhancers
enhance the dissolution rate of active
pharmaceutical ingredient(s).
66

13. Buffers
To provide suitable micro environmental pH to
get improved stability and / or bioavailability.
14. Antioxidants
to maintain product stability, they act by being
preferentially oxidized
15. Chelating agents
added to protect against autoxidation; they act by
forming complexes with the heavy metal ions
which are often required to initiate oxidative
reactions.
67

7. Tablet Manufacturing Methods
The basic three methods for manufacturing of
compressed tablets are :
1. Direct compression method
2. Wet granulation method
3. Dry granulation method
68

Tablet Manufacturing…
1. Direct compression method
 Some granular drug substances like potassium
chloride, calcium gluconate, aspirin possess free
flowing as well as cohesive properties that
enable them to be compressed directly in a
tablet machine with out need of either wet or dry
granulation.
In the direct compression method the tablet
excipients used must be materials with
properties of fluidity and compressibility.
69

 The limitations only a few crystalline drugs can
be directly compressed.
70

Direct Compression: Pros & Cons
Direct compression methods are rather simple;
can often save labor, time, equipment and space
Since the technique requires neither heat nor
moisture, direct compression also enhances
stability.
Direct compression is not suitable for high-dose
drugs that have poor compression and flow
properties
71

Drugs with extremely low bulk density are
difficult to compress directly due to air
entrapment
 They are also sensitive to over-lubrication and
there is a limit to color variation
There is often non-homogeneous distribution of
low-dose drugs due to segregation after blending
(content uniformity)
72

Direct Compression Process Diagram
75

Granulation?
Granulation is the process of collecting
particles together by creating bonds
between them. Bonds are formed by
compression or by using a binding agent
76

Granulation
Two basic techniques are used to granulate
powders for compression into a tablet: Wet
granulation& Dry granulation.
78

2. Dry granulation method
79
Dry granulation processes create granules by
light compaction of the powder blend under low
pressures. The compacts so-formed are
broken up gently to produce granules
(agglomerates). This process is often used when
the product to be granulated is sensitive to
moisture and heat.
Dry granulation can be conducted on a tablet
press using slugging tooling or on a roller
compactor.

80
Dry granulation equipment offers a wide range
of pressures to attain proper densification and
granule formation.
Dry granulation is simpler than wet
granulation, therefore the cost is
reduced. However, dry granulation often
produces a higher percentage of fine granules,
which can compromise the quality or create
yield problems for the tablet.

81
Dry granulation requires drugs or
excipients with cohesive properties, and a 'dry
binder' may need to be added to the
formulation to facilitate the formation of
granules.

82
This process of granulation is also known as
Slugging
Used when the tablet ingredients are sensitive
to moisture or are unable to withstand elevated
temperature during drying.
Dry granulation is the method of choice
provided the tablet ingredients have sufficient
inherent binding or cohesive properties.

The steps are;
weighing,
mixing,
slugging,
dry screening,
lubrication
and compression
83

Dry granulation can be done by two
methods;
SLUGGING
ROLLER
COMPACTION
Large tablet produced
in heavy duty tablet
press.
Powder is squeezed
between two rollers to
produce sheet of material
84
Contd…

a. Roller compaction
Materials are rolled into sheets ("roller
compaction") that can be crushed & sieved into
granules later.
85

b. Slugging
Materials are formed into chunks ("slugs," so
this is called "slugging."). Finally, these bits
are milled and sieved to the appropriate
particle size and compressed into tablets.
86

87
Advantages & disadvantages of dry granulation

88
Dry granulation Process Diagram

3. Wet granulation method
Wet granulation is a process of using a liquid
binder to lightly agglomerate the powder
mixture. The amount of liquid has to be
properly controlled, as over-wetting will cause
the granules to be too hard and under-wetting
will cause them to be too soft and friable.
89

Aqueous solutions have the advantage of being
safer to deal with than solvent-based systems
but may not be suitable for drugs which are
degraded by hydrolysis
90

The powder is mixed with a "granulating
fluid" that helps make the incompressible
powder into a solid mass that can
subsequently be broken up into the
appropriate size particles for compression
into tablets.
useful for fluffy powders, thermo stable
compounds, and powders that may generate a
lot of static charge
91

lots of experience in the industry with this
method.
 multiple steps, lots of equipment = time,
space, money, personnel, materials loss
Water takes longer to dry than organic solvents.
After drying, the granules are screened to
produce appropriately sized particles, which
can then be compressed into tablets.
92

wet granulation Process Diagram
94

Low shear wet granulation processes use very
simple mixing equipment, and can take a
considerable time to achieve a uniformly mixed
state.
High shear wet granulation processes use
equipment that mixes the powder and liquid at a
very fast rate, and thus speeds up the
manufacturing process.
Fluid bed granulation is a multiple-step wet
granulation process performed in the same vessel
to pre-heat, granulate, and dry the powders. It is
used because it allows close control of the
granulation process.
95
8. Major Equipments used for wet granulation

1. High shear mixers/ Rapid Mixer
Granulator
Most of the high-shear granulators consist of a
mixing bowl, a three-bladed impeller, and an
auxiliary chopper.
96

2. Fluid bed dryer
A fluid bed drier, also named fluidized bed
drier is a machine used for drying of
granules/wet mass in both a batch and a
continuous dryer.
By using FBD equipment, a suitable moisture
content in granules can be obtained.
98

99
FLIUD BED.....
Batch Vertical fluidized bed dryer
 A fixed amount of material is fed into the FBD in one
go. Drying is then carried out and when the end point
is reached, the granules are discharged.

Currently instead of fluid bed drier alone, fluid
bed processor is used worldwide and this is
sometimes classified as the one-pot system.
Fluid bed processor refers to material
processing machines using the fluidization
principle. With this equipments;
Drying (powder and granules),
Granulation &
Coating(granule to pellets) can be done.
100
FLIUD BED.....

3. Tray oven Dryer/shelf dryer
The wet granule to be
dried is spread in thin
layers in trays.
The heating is done by
the forced circulation of
large volume of heated
air by means of fans.

Tray oven…
Tray oven dryers have limited output due to
size and batch operation.
The material nearest to the inlet air will dry first
and that nearest to the outlet will dry last
resulting non-uniform drying throughout the
dryer.
Labor costs for loading and unloading the oven
are high.

4. mixers
Tumbler Mixers: For large scale mixing or
batch mixing of granules these
mixers are used. A common type of mixer
consists of metallic container which is
rotated on its horizontal axis by means of a
motor.
Various types of tumbler mixers e.g. cubical,
double cone, Y-cone and bin blender are used.
104

105
Tumbler mixers: double cone blender and V-shaped blender

5. Compression machine
Tablet formation (compression) can be
separated into the two distinct yet equally
important phases
die fill-weight adjustment and
tablet formation.
Pharmaceutical tablets are generally produced
on rotary tablet presses, where upper and lower
punches reside in the upper and lower turret,
respectively.
 The dies are inserted in the die table and
secured by die lock screws.
106

Limitations of Wet Granulation
Because of the large number of processing steps,
it requires a large area with temperature and
humidity control.
It requires a number of pieces of expensive
equipment.
It is time consuming, especially the wetting and
drying steps.
There is a possibility of material loss during
processing due to the transfer of material from
one unit operation to another.
109

Limitations…
There is a greater possibility of cross-
contamination than with the direct-compression
method.
It presents material transfer problems involving
the processing of sticky masses.
It can slow the dissolution of drugs from inside
granules after tablet disintegration if not
properly formulated and processed
110

Advantages & Disadvantages of wet granulation
111

9.Evaluation of Tablets
112
Pharmaceutical tablets are evaluated for their
chemical, physical, and biological
(bioavailability and drug performance)
properties.

1. General appearance
113
Checking the visual identity and overall
elegance.
For control of lot to lot uniformity and
general tablet to tablet uniformity and for
monitoring trouble free manufacturing.
Measurement of tablet size, shape, color,
presence or absence of color, spots, taste,
surface texture, physical flaws and
consistency and legibility of any
identification mark.

Appearance…
114
Non-uniformity of coloring not only lacks
aesthetic appeal but could be associated by the
consumer with non-uniformity of content and
general poor quality of the product
Non-uniformity is generally referred to as
mottling.

Color…
115
Tablet colors are selected to attract consumers
or to uniform the color (if colored API is used
in small quantity).
The color of a product should be uniform (a)
within a single tablet ,(b) from tablet to tablet,
and (c) from lot to lot.

2.Tablet Thickness
116
As a general rule, the thickness should be
controlled to within 5% or less of an established
standard value.
Excessive variation in tablet thickness can
result in problems with packaging as well as
consumer acceptance.
In multi-unit packages such as bottles,
variations in tablet thickness may result in
differences in fill levels for a given number of
dosage units.

Thickness…
117
 In order to maintain product acceptance by the
consumer, variations in tablet thickness must not be
visible to the unaided eye.
 Other tablet quality properties that may be related to
tablet thickness include drug release and
bioavailability (particularly in sustained release
preparations), and tablet friability.

Thickness…
118
Variations in tablet thickness can also indicate
formulation or processing problems.
At a constant compressive load, variations in
tablet thickness are indicative of changes in
die fill and, consequently, tablet weight,
whereas with a constant die fill, thickness
variations reflect changes in compressive
force.

Thickness…
119
Tablet thickness is often used as one of
several in-process tests and is monitored at
regular intervals during the compressing stage
of tablet manufacture.
If appropriate, adjustments can then be made
by machine operators to maintain tablet
thickness within specifications.

Thickness…
120
The thickness of individual tablets are
generally measured with a micrometer, or
Digital calipers which provide accurate single
tablet thickness measurements.

3. Hardness
121
Once ejected from the compression machine, a tablet
requires a certain amount of mechanical
strength to withstand the shocks of handling in its
manufacture, packing, shipping, and dispensing.
The tablets may also be able to withstand a
reasonable amount of abuse imparted
by the consumer, e.g., a partially filled bottle
bounding around in a purse or pocket.

Hardness…
122
The definition and measurement of tablet hardness
have evolved over the years. Historically,
tablet strength was determined by breaking a tablet
between the second and third fingers
using the thumb as a fulcrum. If there was a sharp
snap, the tablet was considered to have acceptable
strength.

Hardness…
123
It is the force at which the tablet crushes.
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, packaging and
shipping operations.

Hardness…
Scleuniger hardness tester
Hardness can be measured in Kg/cm2, kg/in2, lb/in2, kilopond,
Newton(N)
Instrument used
Monsanto hardness tester
Strong cobb hardness tester
 Pfizer hardness tester
Scleuniger hardness tester
Generally minimum required hardness is 4 kg/in2
Monsanto hardness tester
Strong cobb hardness tester
Pfizer hardness tester

Hardness…
Tablet hardness is not an absolute indicator of
strength since some formulations, when
compressed into very hard tablets may produce
chipping, capping and lamination problems.
Therefore another measure of tablet strength
i.e, friability is often measured.
126

4.Friability Test
 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 roche friabilator is used to evaluate the
ability of the tablet to withstand abrasion in packaging, handling,
and shipping.
127

Friability…
Method
1. European pharmacopeia
For tablets weighing up to 650 mg each, take a
sample of twenty tablets ; for tablets weighing
more than 650 mg each, take ten tablets.
Place the tablets on a sieve no. 1000 and remove
any loose dust with the aid of air pressure or a soft
brush. Accurately weigh the tablet sample and
place the tablets in the drum. Rotate the drum 100
times and remove the tablets.
128

Friability…
Remove any loose dust from the tablets as before.
If no tablets are cracked, split or broken, weigh
the tablets to the nearest milligram.
Calculate the percentage of friability as follows.
Friability= (%W/W) = (W1-W2 )100%
W1
Generally the test is run once. If the results are
doubtful or if the mass loss is greater than 1 per
cent, repeat the test twice and determine the mean
of the 3 tests. A maximum loss of 1 per cent of the
mass of the tablets tested is considered to be
acceptable for most products
129

Friability…
2.USP/BP pharmacopeia
For tablets with a unit weight equal to or less
than 650 mg, take a sample of whole tablets
corresponding as near as possible to 6.5 g.
For tablets with a unit weight of more than 650
mg, take a sample of 10 whole tablets.
The tablets should be carefully dedusted prior to
testing.
In case of hygroscopic tablets, an appropriate
humidity controlled environment is required for
testing.
130

Friability…
Generally, the test is run once. Accurately weigh the
tablet sample, and place the tablet in the drum. Rotate
the drum 100 times, and remove the tablets. Remove
any loose dust from the tablets as before, and
accurately weigh.
Calculate the percentage of friability as follows.
Friability= (%W/W) = (W1-W2 )100%
W1
 When capping is observed during the friability testing, tablets
should not be considered acceptable, regardless of the
percentage weight loss.
131

5. Disintegration Test
It is the time required for the tablet to break into
granules or 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 granules or
particles.
132

Disintegration…
Disintegration is considered to be achieved
when:
a) no residue remains on the screen, or
b) if there is a residue, it consists of a soft mass
having no palpably firm, unmoistened core, or
c) only fragments of coating (tablets) remain
on the screen.
134

Disintegration…
Method
 In each of the 6 tubes, place one tablet
and, if prescribed, add a disc; suspend the assembly in the beaker
containing the specified liquid. Maintain the temperature at 35-
39°C.
 This system is made to move up and down through a distance of 5 to
6 cm at a frequency of 28 to 32 cycles per minute.
 Operate the apparatus for the prescribed period, withdraw
the assembly and examine the state of the tablets.
 To pass the test, all the tablets must have disintegrated.
135

Disintegration…
136
SN Tablet Type General Recommended Test Conditions
1 Uncoated Tablet Not More Than 15 min, in water with/without
disc at 35±2°C
2 Film coated tablets Not More Than 30 min, in water with/without
disc at 35±2°C
3 Enteric coated tablets Intact for 1 hr in 0.1N HCL and disintegrate
within 2 hrs in mixed 6.8 PH of phosphate
buffer. According to USP 1hr in simulated
gastric fluid, then in simulated intestinal fluid.
4 Dispersible/ soluble
tablets
Within 3 min in water at 25±1°C (IP) and 15-
25°C (BP)
5 Effervescent tablet 5 min in 250ml water at 20-30°C (IP) & 5min in
200ml water at 15-25°C (BP)
6 Buccal or sublingual Not applicable but dissolves within 15-30 min.

6. Weight Variation Test
 It is performed to check the uniformity of the tablet. The weight
variation test would be a satisfactory method for determining drug
content uniformity of drug distribution. In practice this test is
performed by taking 20 tablets, from a batch. 20 tablets are weighed at
a time and the average weight is taken. Then the tablet is weighed
individually.
 For a tablet to pass the test not more than 2 tablets should lie out of the
specified percentage and if no tablet differs by more than two times the
percentage limit.
137
United States
Pharmacopeia
Indian Pharmacopeia % deviation
130mg or less 80mg or less 10
130-324mg 80-250mg 7.5
324mg or more 250mg or more 5

7. Dissolution
 Disintegration time determination is a useful tool for production
control, but disintegration of a tablet does not imply that the
drug has dissolved.
 A tablet can have a rapid disintegration time yet be biologically
unavailable. The dissolution rate of the drug from the primary
particles of the tablet is the important factor in drug absorption
and for many formulations is the rate-limiting step.
 Therefore, a dissolution time is more indicative of the
availability of a drug from a tablet than the disintegration test.
138

Dissolution...
 The dissolution test measures the rate of dissolution
of the drug from the dosage form in vitro. It is usually
expressed as the extent of dissolution (percent of drug
content) of the drug occurring after a given time under
specified conditions.
 This test is necessary to help in the prediction of the
behavior of the drug in the dosage form after ingestion
and as a quality control tool for checking batch-to-
batch uniformity.
139

Dissolution...
 Different types of apparatus are used to study the
dissolution test of the tablet.
 apparatus I (paddle) and apparatus II(basket) are
commonly used. called basket dissolution
apparatus and paddle dissolution apparatus
140

10. Tableting Problems/deffects & Remedies
141
During the normal or routine process of tableting,
defects may occur due to formulation problem or
due to compression equipment or due to both.
An ideal tablet should be free from any visual
defect or functional defect.
Majority of visual defects are due to inadequate
fines or inadequate moisture in the granules ready
for compression or due to faulty machine setting.
Functional defects are due to faulty formulation.

Tableting Problems…
Solving many of the manufacturing problems
requires;
an in–depth knowledge of granulation
processing and tablet presses,
and is acquired only through an exhaustive
study and a rich experience
142

Tableting Problems…
The defects are :
1. Capping
2. Lamination
3. Chipping
4. Cracking
5. Sticking/filming
6. Picking
7. Mottling
8. Weight variation
9. Hardness variation
10.Double Impression
11.Binding
143

1. Capping
Capping: is the partial or complete separation of
the top or the bottom crowns of a tablet from the
main body of the tablet.
Usually capping and lamination problems are
apparent immediately after compression or even
hour or days latter.
Subjecting tablets to the friability test is the
quickest way to reveal such problems.
144

Capping…
Reason: entrapment of excess air in the granules
during compression. Excess of fines powder will
entrap the air during compression.
If the granules are light and fluffy this type of
problems are encountered frequently.
New set of punches and dies are very tightly
fitted; i.e the clearance is very negligible hence
air cannot come out.
145

SN CAUSES REMEDIES
1.
Large amount of fines in the
granulation
Remove some or all fines
2.
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.
Moisture content should be kept
within 1-2%
3.
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.
146

Related to ‘Machine’ (Dies, Punches and Tablet Press)
147
SN CAUSES REMEDIES
1. Poorly finished dies
Polish dies properly.
For tightly fitted punches & dies; punch
punch diameter should be reduced by
by 0.005 inches.
2.
Deep concave punches or
beveled-edge faces of punches. Use flat punches.
3.
Lower punch remains below the
the face of die during ejection.
Make proper setting of lower punch
during ejection.
4.
Incorrect adjustment of sweep-off
off blade
Adjust sweep-off blade correctly to
facilitate proper ejection.
5. High turret speed
Reduce speed of turret (Increase dwell
dwell time).

2. Lamination
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.
148

Related To Formulation (Granulation)
149
SN.
CAUSES
REMEDIES
1.
Oily or waxy materials in
granules
Modify mixing process. Add
adsorbent or absorbent.
2.
Too much of hydrophobic
lubricant e.g.: Magnesium-
stearate.
Use a less amount of lubricant
lubricant or change the type of
of lubricant.

Related to machine (dies, punches and tablet press)
150
S.
N
CAUSES REMEDIES
1.
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°.
2. Rapid decompression
Use pre-compression step.
Reduce turret speed and reduce
the final compression pressure.

Related to formulation
151
SN CAUSES REMEDIES
1.
Large amount of fines in the
granulation
Remove some or all fines through
100 to 200 mesh screen
2.
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.
3. Not thoroughly dried granules. Dry the granules properly.
4
Insufficient amount of binder or
improper binder.
Increasing the amount of binder OR
Adding dry binder such as pre-
gelatinized starch, gum acacia,
powdered sorbitol, PVP, hydrophilic
silica or powdered sugar.
5 Insufficient or improper lubricant.
Increase the amount of lubricant or
change the type of lubricant.

3. 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.
152

153
S N CAUSES REMEDIES
1.
Sticking on punch
punch faces
Dry the granules properly or
increase lubrication
2. Too dry granules
Moisten the granules to
plasticize. Add hygroscopic
substances
3.
Too much binding
binding causes
chipping at bottom
Optimize binding, or use dry
binders

Related to machine press)
154
S N
CAUSES REMEDIES
1.
Groove of die worn at
compression point.
Polish to open end, reverse
reverse or replace the die.
2.
Barreled die (center of the die
wider than ends)
Polish the die to make it
cylindrical
3.
Edge of punch face turned
inside/inward.
Polish the punch edges
4.
Concavity too deep to compress
compress properly.
Reduce concavity of punch
punch faces. Use flat
punches.

4. Cracking
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.
155

156
S N CAUSES REMEDIES
1.
Large size of
granules.
Reduce granule size. Add fines.
2. Too dry granules.
Moisten the granules properly and add proper
proper amount of binder.
3. Tablets expand Improve granulation. Add dry binders.
4.
Granulation too
cold.
Compress at room temperature.

Related to machine
157
S N CAUSES REMEDIES
1.
Tablet expands on ejection due
to air entrapment.
Use tapered die.
2.
Deep concavities cause
cracking while
removing tablets
Use special take-
off.

5. 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.
158

Sticking related to formulation
159
S N
CAUSES REMEDIES
1.
Granules not dried properly Dry the granules properly. Make moisture
moisture analysis to determine limits.
2.
Too little or improper
lubrication
Increase or change lubricant.
3. Too much binder
Reduce the amount of binder or use a
different type of binder.

Related to machine
160
S N CAUSES REMEDIES
1.
Concavity too deep for
granulation.
Reduce concavity to
optimum.
2. Too little pressure. Increase pressure.
3. Compressing too fast. Reduce speed.

6. Picking
Picking: is a form of sticking in which a small
portion of granulation sticks to the punch face and
grows with each revolution of the press, picking out
a cavity on the tablet face.
The problem is more prevalent on the upper punch faces
than on the lower ones.
Reason: Picking is of particular concern when punch
tips have engraving or embossing letters, as well as the
granular material is improperly dried.
161

162
S N CAUSES REMEDIES
1.
Excessive moisture in granules. Dry properly the granules, determine optimum
optimum limit.
2.
Too little or improper
lubrication.
Increase lubrication; use colloidal silica as a
‘polishing agent’, so that material does not cling
cling to punch faces.
3.
Low melting point substances,
substances, may soften from the
the heat of compression and
lead to picking.
Add high melting-point materials. Use high
meting point lubricants.

Picking related to machine
163
S N CAUSES REMEDIES
1.
Rough or scratched punch
faces.
Polish faces to high luster.
2.
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.
3.
Bevels or dividing lines too
deep.
Reduce depths and sharpness.
4.
Pressure applied is not
enough; too soft tablets.
Increase pressure to optimum.

7. Mottling
Mottling: is the term used to describe an unequal
distribution of color on a tablet, with light or dark spots
standing out in an otherwise uniform surface.
Reason: One cause of mottling may be a colored drug,
whose color differs from the color of excipients used for
granulation of a tablet.
164

The causes and remedies
165
SN CAUSES REMEDIES
1.
A colored drug used along with
colorless or white-colored
excipients.
Use appropriate colorants.
2.
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.
3.
Improperly mixed dye,
especially during ‘Direct
Compression’.
Mix properly and reduce size if it is of a larger
size to prevent segregation.
4.
Improper mixing of a colored
binder solution.
Incorporate dry color additive during powder
blending step, then add fine powdered adhesives
such as acacia and tragacanth and mix well and
finally add granulating liquid.

8. Uniformity of Weight (Mass)
It is difference in weight of tablet which are
punched in same machine and same batch. Weight
of tablet is determined by amount of granules in
the die prior to compression.
Therefore anything that can alter the die filling
process can alter weight and weight variation.
166

Weight…
167
SN CAUSES REMEDIES
1.
Difference in granule size and
size distribution
Maintain uniform granules size and size
distribution of granules
2. Poor flow property of granules Increse flow property by using suitable glidant
3. Increased moisture content Decrease moisture content
4.
Punch variation: improper
alignment and unequal length of
lower punches
Use punches having uniform length

9. Hardness Variation
It is the difference in hardness of tablet which are
compressed by same machine in same batches.
Hardness of tablet depend on the amount of
material and space between upper and lower
punch at the same movement of compression.
The causes are same as that of weight variation.
168

10. 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. If the upper punch is
uncontrolled, it can rotate during the short travel to the
final compression stage and create a double
impression.
169

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’.
170

171
S N. CAUSE REMEDIES
1.
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.

11.Binding
Binding in the die or difficult ejection is usually
due to insufficient lubrication.
It is the resistance of the tablet to ejection from
the die. This can cause the tablet press to labor
and squeak producing tablets with rough edges
and vertical score marks on the edges.
172

Binding…
This may be overcome by;
Increasing lubrication
Using a more efficient lubricant
Improving the distribution of the lubricant by
screening through an 30-mesh screen and mixing with
a portion of fines screened from the granulation
Reducing the size of the granules
Increasing the moisture content of the granulation
Compressing at a lower temperature and/or humidity
173

tablet manufacturing process.pptx

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to tablet manufacturing process.pptx

Similar to tablet manufacturing process.pptx (20)

Recently uploaded

Recently uploaded (20)

tablet manufacturing process.pptx

Editor's Notes