PHARMACEUTICAL

TABLET

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 Tablets
Tablets may be defined as solid pharmaceutical dosage forms
containing drug substance(s) with or without suitable diluents and
prepared either by compression or molding methods. They vary in
shape and differ greatly in size and weight, depending on amount of
medicinal substances and the intended mode of administration.

Solid medicaments may be administered orally as powders, pills,

cachets, capsules or tablets. These dosage forms contain a quantity
of drug which is given as a single unit and they are known
collectively as solid unit dosage forms.

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 Tablet Ingredients

In addition to the active or therapeutic ingredient, tablets contain a

number of inert materials. The latter are known as additives or
excipients. Different excipients are-

1. Diluent
2. Binder and adhesive
3. Disintegrants
4. Lubricants and glidants
5. Coloring agents
6. Flavoring agents
7. Sweetening agents

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 1. Diluents
A. Primary reason is to increase the bulk of the tablet. Generally, a
tablet weigh at least 50mg. Sometimes the active ingredient
used may be of 0.05mg (Levothroid tablet, 0.05mg/tablet,
tablet for hormonal disorder treatment). In this case diluent is
used to give the necessary weight for the tablet.
B. Secondary reason is to provide better tablet properties such as-
➢improve cohesion,
➢to permit use of direct compression manufacturing or
➢to promote flow
➢to adjust weight as per die capacity.

Commonly used tablet diluents-

Dicalcium phosphate, calcium sulfate, lactose, cellulose, kaolin,
mannitol, sodium chloride, dry starch, sucrose, sorbitol and
powdered sugar. 4
 2. Binders
Agents used to impart cohesive qualities to the powdered material
are referred to as binders. These materials are added either dry or
in wet form. They impart a cohesiveness to the tablet formulation
which insures the tablet remains intact after compression, as well
as it improves the free flowing qualities by the formulation of
granules of desired hardness and size.

Examles are-
i. Cellulose derivatives: Methyl cellulose, Hydroxy propyl
methyl cellulose, Hydroxy propyl cellulose
ii. Gelatin: 10-20% solution
iii. Glucose: 50% solution
iv. Starch paste: 10-20% solution
v. Sodium alginate
vi. Sorbitol 5
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 celluloses, they change the
powdered material to granules and the residual moisture
retained enables the materials to adhere together when
compressed.

A granulating agent provides proper moisture to convert fine

powder into damp mass Traditional granulating agents such as
starch, gelatin, sucrose, acacia, hydroxypropyl
methylcellulose and polyvinyl pyrrolidone have been used to
provide a freely flowing granulation mixture, tabletability,
aqueous solubility or dispersibility of the medically effective
ingredient, and so forth. 6
 3. Disintegrant
A disintegrant is a substance, or a mixture of substances added
to a tablet to facilitate its breakup or disintegration when it
comes in contact with aqueous fluid after administration.
Materials serving as disintegrants have been chemically
classified as starches, clays, celluloses.

Starch (5%) is digested, but if more rapid disintegration is

desired, this amount may be increased to 10 or 15%. A new
group of materials known as "superdisintegrants" are recently
gained in popularity as disintegrating agents. The name comes
from their use at low levels (2-4%) at which the disintegrants
are completely effective.
Example- sodium starch glycolate (SSG), crospovidone (CP)
and croscarmellose sodium (CCS)
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 4. Lubricant and Glidant
Lubricants have a number of functions in tablet manufacture-
i. They prevent adhesion of the tablet material to the surface
of the dies and punches,
ii. reduce interparticle friction,
iii. facilitate the ejection of the tablets from the die cavity,
iv. reduce the friction between the walls of the tablets or walls
of the die cavity when the tablet is ejected and may improve
the rate of flow of the tablet granulation.

Commonly used lubricants include talc, magnesium stearate,

calcium stearate, stearic acid, and hydrogenated vegetable
oils. Most lubricants with the exception of talc are used in
concentrations less than 1%. When used alone, talc may require
concentrations as high as 5%. 8
A glidant is a substance which improves the flow characteristics of
a powder mixture by reducing friction between the particles. These
materials are always added in the dry state just prior to
compression (i.e, during the lubrication step).

Silicon dioxide is the most commonly used glidant and is generally

used in low concentrations of 1% or less. Stearic acid, Magnesium
stearate, Talc, PEG (Polyethylene glycols), Surfactants etc. are
commonly used glidants.

Antiadherent: Reduce the sticking of the powder materials on the

faces of the punches or die walls.

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 5. Coloring Agents
The use of colors and dyes in a tablet has three purposes:
(1) Masking of off colored drugs
(2) Product Identification
(3) Production of more elegant product

All coloring agents must be approved and certified by FDA. Two

forms of colors are used in tablet preparation– FD (Food and Drug)
& C (Cosmetic) and D & C dyes. These dyes are applied as solution
in the granulating agent or Lake form of these dyes. Lakes are dyes
absorbed on hydrous oxide and employed as dry powder coloring.
Example: FD & C yellow 6-sunset yellow
FD & C yellow 5- Tartrazine
FD & C green 3- Fast Green
FD & C blue 1- Brilliant Blue
FD & C blue 2 - Indigo carmine 10
D & C red 3- Erythrosine.
 6. Flavoring agents
They are basically applied to the chewable tablet that gets
dissolved in the mouth, imparting pleasant taste, and mask off
taste, e.g, mannitol or lactose, artificial sweetening agents
(aspartame, sucralose, and alitame) may be included.

Sweeteners other than the sugars have the advantage of reducing

the bulk volume considering the quantity of sucrose required to
produce the same degree of sweetness. Being present in small
quantities, they do not markedly affect the physical
characteristics of the tablet granulation.
Oil flavors are added just before the compression step. This is
because the flavoring oil may vaporized during the heating as
well as it is very sensitive to moisture.
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 7. Sweetening agents
Some sweeteners may come from the diluent.

a. For chewable tablets: Sugar, mannitol.

b. Saccharine (artificial sweetener): It is 500 times sweeter than
sucrose. But the after taste is bitter and also carcinogenic.
c. Aspartame (artificial sweetener) shows lack of stability in
presence of moisture. Aspartame is about 180 times sweeter
than sucrose.

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 B. Different Types of Tablets
1. Tablets ingested orally
1. Compressed tablet: These tablets are formed by compression and contain
no special coating. They are made from powdered, crystalline or granular
materials, alone or in combination with suitable excipients.
These tablets contain water soluble drugs which after swallowing get
disintegrated in the stomach and its drug contents are absorbed in the
gastrointestinal tract and distributed in the whole body. e.g. Paracetamol
tablet (fever, pain etc.).

2. Multiple compressed tablet: For incompatible components these are:

A) Layered tablet- either two layered (for two components) or three layered
(for three components) tablet.
B) Compressed coated type- either tablet within a tablet. Tablet in this
category are usually prepared for two reasons-
a. To separate physically or chemically incompatible ingredients.
b. To produce repeat action or prolong action product.

e.g., Bilayer tablet formulation of Metformin hydrochloride and Gliclazide

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for diabetes treatment.
 Layer Tablet
Compressed coated type
(Tablet in a tablet)

used to protect hygroscopic, light-sensitive, oxygen- or acid-labile drugs

Repeat-action tablets are one type of extended-release dosage form.

They usually contain two single doses of medication, one for immediate
release and one for delayed release. Typically, the immediately released
drug comes from the exterior portion of the tablet.

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[

3. Repeat action tablet: A repeat-action tablet is a type of modified-

release drug product that is designed to release one dose of drug
initially, followed by a second dose of drug at a later time. Sugar
coated or multiple compressed tablets are used for this purpose. The
core tablet is usually coated with shellac (natural polymer) or an
enteric polymer so that it will not release its drug in stomach but
intestine.
e.g. Dexchlor (antihistamine drug used for Non-seasonal or
Perennial and seasonal allergic rhinitis).

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Shellac
4. Delayed release tablet: This dosage form is intended to release the
drug after some time delay or after the tablet has passed one part of the GIT
into another. All enteric coated tablets are type of delayed action tablet but
all delayed action tablets are not enteric or not intended to produce enteric
action. As a enteric coating material polyvinyl acetate pthalate, cellulose
acetate pthalate are used. These polymers contain ionizable functional groups
that render them water-soluble at a specific pH value.

e.g. Enteric coated Bisacodyl tablet (Relieving occasional constipation and

irregularity).

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5. Film coated tablet: This is an attractive method where a thin
polymer-based coat applied to a tablet. Polymers such as hydroxy
propyl cellulose, hydroxy propyl methyl cellulose, and colloidal
dispersion of ethylcellulose are commonly used. A 30% dispersion of
ethylcellulose is known as aquacoat.
The film coating protects the medicament from atmospheric effects.
Film coated tablets are generally tasteless, having little increase in the
tablet weight and have less elegance Advantage of film coated over
sugar coated tablets is better mechanical strength and flexibility of
the coating, little increase in tablet weight.
e.g. Metronidazole tablet (to treat bacterial infections of the stomach,
skin, joints, and respiratory tract)

6. Chewable tablet: These are the tablets which are required to be

broken and chewed in between the teeth before ingestion. These
tablets are given to the children who have difficulty in swallowing
and to the adults who dislike swallowing. Used for large tablet of
antacid. Bitter or foul testing drugs are not suitable for this type
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tablet. e.g. Antacid tablet (neutralize acid in the stomach).
2. Tablets used in oral cavity
1. Sublingual tablet: A sublingual tablet is usually a flat tablet that is small
enough to fit under our tongue. The active ingredient of the sublingual tablet is
typically absorbed directly by the saliva and the tablet dissolves very rapidly and
absorbed through mucosa. Certain medications and vitamins are taken
sublingually. e.g. Vicks Menthol tablet (to get relieved from throat irritation).

2. Buccal tablet: These tablets are small, flat and are intended to be held
between the cheek and teeth or in cheek pouch (buccal tablet). Drugs used by
this route are for quick systematic action. The tablets are designed not to be
disintegrate but slowly dissolve.
e.g. Vitamin-C tablet (treatment of common cold, gum diseases, acne or other
skin infections etc.)

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3. Troches or lozenges : Used in the oral cavity to exert local effect in mouth
and throat. They are commonly used to treat sore throat or to control coughing
in common cold. They may contain local anesthetics, antiseptic, antibacterial
agents, astringent and antitussive. The tablets are dissolved slowly over a period
of 30 minutes.
e.g.,oral clotrimazole is used to treat and prevent yeast infections of the mouth
and throat.

4. Dental cone: These tablets are designed to be placed in the empty socket
remaining after tooth extraction. Main purpose is to prevent microbial growth in
the socket or to reduce bleeding by an astringent or coagulant containing in this
tablet.

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3. Tablets administered by other route
Implantation tablet (not more than 8 mm in length; applied in subcutaneous
implantation for drug delivery) is designed for substances implantation to
provide prolonged drug effect from one month to a year. These methods require
special surgical technique for implantation and discontinuation of therapy.
Generally used for administration of growth hormone to food producing animal.

4. Tablets used to prepare solution

1. Effervescent tablet: Tablets are designed to produce a solution rapidly with
the release of carbon dioxide. The tablets are prepared by compressing the
active ingredient with mixture of organic acid such as citric acid or tartaric acid
and sodium bicarbonate. Another example is Dispirin tablet (Aspirin)
(headache, migraine, toothache, sore throat etc.)

2. Dispensing tablet: Tablets are intended to be added to a given volume of

water to produce a solution of a given drug concentration.
e.g. Enzyme tablet (Digiplex) (loss of appetite, indigestion, digestive
supplement during pregnancy etc.)
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3. Hypodermic tablet: These tablets are composed of one or more drugs with
water-soluble ingredients. Drug is added to sterile water to prepare sterile
solution, which is injectable. e.g., Morphine (to treat moderate to severe pain).

4. Tablet triturates: Usually are made from moist materials using a triturate
mold, which gives them the shape of cylinder. Such tablet must be completely
and rapidly soluble. e.g. Glitazones (anti-diabetic drug, used along with a
proper diet and exercise program to control high blood sugar in patients with
type 2 diabetes).

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Methods of Tablet
Manufacturing

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 Manufacturing of Tablets
Manufacture of tablets involves certain well defined steps: namely-
1. Pulverization and mixing.
2. Granulation.
3. Compression.
4. Coating (if required)
1. Pulverization and mixing-
a) In this step the different solid / powder ingredients are reduced to
the same particle size since particles of different sizes will
segregate while mixing.
b) Various equipments like Cutter mill, Hammer mill, Roller mill
and Fluid energy mill is required to reduce the large lumps.
2. Granulation Technology
Granulation: It is the process in which primary powder particles
are made to adhere to form large multi-particle entities.
Range of size: 0.2 mm to 4 mm. (0.2 mm to 0.5 mm) 24
Objectives-
➢ To enhance the flow of powder.
➢ To produce dust free formulations and produce uniform mixtures.
➢ To improve compaction characteristics.
➢To eliminate poor content uniformity of mix.
➢To avoid powder segregation. As Segregation may result in weight variation.

(a) Wet Granulation

Step-I Milling of the drug and excipients
✓Milling of the active ingredients, excipients etc. are milled to obtain a
homogeneity in the final granulation.
✓If the drug is given in solution then during drying it will come up to
the surface. To avoid this problem drug is mixed with other excipients in
fine state.
Step-II Weighing
✓Weighing should be done in clean area with provision of air flow system.
✓In the weighing area all the ingredients must not be brought at a time to
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avoid cross contamination.
 Step-III Mixing Commonly used blenders are:
(a) Double cone blender
(b) V–blender
(c) Ribbon blender
(d) Planetary mixer
Any one of the blender may be used to mix dry powder mass.
Step-IV Wet Massing
• Wet granulation forms the granules by binding the powders together
with an adhesive.
• Binder solutions can be added in two methods-

When a small When a large

quantity of quantity of
solvent is solvent is
permissible, required,
Method-I is Method-II is
adopted adopted
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▪ If granulation is over-wetted, the granules will be hard, requiring
considerable pressure to form the tablets, and the resultant tablets may
have a mottled appearance.

▪ If the powder mixture is not wetted sufficiently, the resulting granules

will be too soft, breaking down during lubrication and causing difficulty
during compression.

Step-V Wet Screening

Wet screening process involves converting the moist mass into coarse,
granular aggregates by–
✓ passage through a hand screen (in small scale production) or,
✓ passage through an oscillatory granulator of hammer mill equipped
with screens having large perforations (6–8 mesh screen).
Purpose
– To increase particle contact point
– To increase surface area to facilitate drying.
Step-VI Drying
- Drying is usually carried out at 60 0C. Depending on the thermolabile
nature of the drug the temperature can be optimized.

-Drying is required in all wet granulation procedures to remove the

solvent, but is not dried absolutely because it will pose problems later
on. Hence, certain amount of moisture (1 – 4 %) is left within the
granules – known as the residual moisture.

Methods: Drying can be carried out

Tray dryers – it may take 24 hrs of drying
Truck dryers – the whole cabinet can be taken out of the dryer
Fluid-bed dryer – carry out drying in 30 mins.
Step-VII Dry Screening
After drying, the granules are made monosize by passing through mesh
screen. For drying granules the screen size to be selected depends on
the diameters of the punch. 28
Step-VIII Lubrication of granules
➢ After dry granulation, the lubricant is added as a fine powder.
It usually, is screened onto the granulation through 60 or 100
mesh nylon cloth to eliminate small lumps as well as increase the
covering capacity of the lubricant.

➢ The lubricant is blended very gently using tumbling action to

maintain the uniform granule size.

➢ Too much fine powder is not desirable because fine powder

may not feed into the die uniformly causing variation in weight
and density.

➢ Since, the very nature of lubricant produce hydrophobic

surface on the particle hence over blending prevents the inter
granule bonding that takes place during compression. 29
 V-BLENDER
The V-Blender is made of two hollow cylindrical shells joined at an
angle of 75° to 90°. The blender container is mounted on trunnions
to allow it to tumble. As the V-blender tumbles, the material
continuously splits and recombines, with the mixing occurring as the
material free-falls randomly inside the vessel. The repetitive
converging and diverging motion of material combined with
increased frictional contact between the material and the vessel's
long, straight sides result in gentle yet homogenous blending.

Top-Bottom Fill
Or
Side to Side Fill
Rotation Rate: 10 rpm

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 Fluid Bed Spray Granulator
Principle
In wet granulation, when the liquid feed is sprayed through an
atomizing nozzle into, or onto the surface of a fluidized bed (containing
suspended powders in air stream), discrete liquid droplets are formed
which may either dry and form new discrete particles, or combine with
existing bed particles in one of two ways:
a) the liquid coats the particle surface, dries, before a collision with a
second particle is possible and consequently produces a growth
layer, or crust, of the dissolved feed substance;
b) wet particles coalesce and the liquid between them dries to form
solid bridges and thus produces an agglomerate of two or more
primary particles. Thus the granules are formed which are then
dried and collected separately.

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Operation
In the fluidized bed spray granulator, hot air or gas is passed at high pressure
through a perforated bottom of the container. The container contains powder
mixture, from which granules are to be formed. The powders are suspended in the
stream of hot air (conditioned air) and are lifted from the bottom. This condition is
called fluidized state. For (wet) granulation, granulating liquid is sprayed through a
nozzle. The nozzle can be placed at the bottom of the vessel or it can be sprayed
from the top. When the spray operation is done through bottom it is called bottom
spray and in case of top position it is called top spray. The hot air is surrounded
every granules formed to completely suspend and dry them. Thus the granules are
uniformly dried and separated.
At the top, exhaust filter bags separate the product from the process air before
the air exits into the atmosphere through an outlet air duct (desired airflow is
created by turbine fan suction). The ideal filter material should retain all of the
product particles in the container while allowing process air to pass through.

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Advantages of Fluidized Bed Granulator
•Fluidized bed granulator is a one unit system and thus saves labor cost, transfer
loss and time.
•Heat transfer in fluidized bed granulator is 2-6 times greater than that generated
by tray dryer.
•The process can be automated once parameters are optimized. 33
 (b) Dry Granulation
Dry granulation is followed in situations where-
✓ the effective dose of a drug is too high for direct compaction and
✓ if the drug is sensitive to heat, moisture or both, which precludes wet
granulation. e.g. many aspirin and vitamin formulations are prepared
for tableting by compression granulation.
Steps of granulations
Milling Weighing Screening Blending Slugging
Granulation (Dry) Lubrication Compaction.
Advantages of dry granulation over wet granulation
❖ No application of moisture (required in wet granulation) and heat (for drying).
So the drugs susceptible to either moisture or heat or both can be made by dry
granulation. e.g. calcium lactate cannot be used by wet granulation.
❖ Dry granulation involves less steps and hence less time is required than that of
wet granulation.
❖ Less steps requires less working space and energy.
❖ Since popularity of wet granulation is more that dry granulation because former
will meet all the physical requirement for the compression of good tablets.
3. Direct Compression Method
Steps of compression
Milling Weighing Sieving Blending Compression
Direct compression consists of compressing tablets directly from
powdered materials without modifying physical nature of materials. This
method is applicable for crystalline chemicals having good compressible
characteristic and flow properties such as: potassium salt (chlorate,
chloride, bromide), sodium chloride, ammonium chloride, etc. If
necessary, direct compression vehicles can be used which are having
good flow and compressible characteristics.
Commonly used directly compression diluents are- Microcrystalline
cellulose, Spray dried lactose, Starch, Sugar, Dicalcium phosphate
dihydrate (Di-Tab), Mannitol etc.
Advantages: Disadvantages:
i) It is much more quicker than any of the i) Unsuitable for low dosage
previous process ii) Weak content uniformity
ii) Minimum number of steps are required. iii) Need good flow ability
iii) For water and solvent and heat sensitive APIs
 Tablet Compression
It can reduce the volume by apply pressure, particle in die are re-arrange,
resulting a closer packing structure and reduce space and at certain lode
reduced space and increase interparticulate friction will prevent farther
interparticulate friction.
Elastic deformation: Either whole or a part can change their shape
temporarily.
Plastic deformation: Change shape permanently.
Particle fragmentation: Fracture into a number of smaller discrete
particles.
Find new position- decrease the volume of powder bed- when force
increase new particle again undergo deformation and particle-particle
bonds can formed.
Time of loading: Deformation of particle are time independent process in
Elastic & Plastic deformation.
Deformation is time dependent, when its behavior is referred to
Viscoelastic & Viscous deformation.
Degree of deformation: Some quantitative change in shape.
Mode of deformation:- type of shape change.
Basic Component of Compression Machine
Head– Contain upper punches, dies, lower punches.
Body– Contain operating machineries.
Hopper– Holding feeding granules.
Dies– Define size, shape of tablet.
Punches– For compression within dies.
Cam tracks– Guiding the movement of punches.
Feed frame– Guiding the granules from hopper to dies.
Upper turret– Holds the upper punches.
Lower turret– Hold the lower punches.
Die table– Contain the dies.