1. Prepared by: Ankita Yagnik
Akshar-preet Institute of pharmacy,
Tablet is defined as a
dosage form containing
medicaments with or
According to the Indian
are solid, flat or biconvex
dishes, unit dosage form,
prepared by compressing
a drug or a mixture of
drugs, with or without
They are unit dosage form and offer the greatest
capabilities of all oral dosage form for the greatest dose
precision and the least content variability.
Cost is lowest of all oral dosage form.
Lighter and compact.
Easiest and cheapest to package and strip.
Easy to swallowing with least tendency for hang-up.
Sustained release product is possible by enteric coating.
Objectionable odour and bitter taste can be masked by
Suitable for large scale production.
4. Greatest chemical and microbial stability over all
oral dosage form.
Product identification is easy and rapid requiring no
additional steps when employing an embossed
and/or monogrammed punch face.
Difficult to swallow in case of children and
Some drugs resist compression into dense compacts,
owing to amorphous nature, low density
Drugs with poor wetting, slow dissolution properties,
optimum absorption high in GIT may be difficult to
formulate or manufacture as a tablet that will still
provide adequate or full drug bioavailability.
Bitter testing drugs, drugs with an objectionable odor
or drugs that are sensitive to oxygen may require
encapsulation or coating. In such cases, capsule may
5. Different types of Tablets
(A) Tablets ingested orally:
1. Compressed tablet, e.g. Paracetamol tablet
2. Multiple compressed tablet
3. Repeat action tablet
They are one type of extended or modified release
tablet. Usually contain two single doses of
medication one for immediate and one for delayed
4. Delayed release tablet, e.g. Enteric coated
5. Sugar coated tablet, e.g. Multivitamin tablet
6. Film coated tablet, e.g. Metronidazole tablet5
6. (B) Tablets used in oral cavity:
1. Buccal tablet, e.g. Vitamin-c tablet
These tablets are placed in side of the cheek for
slow release of the medicament.
2. Sublingual tablet, e.g. Vicks Menthol tablet
These tablets are placed below the tongue.
3. Troches or lozenges
These tablets should not disintegrate but dissolve
slowly in the mouth to provide continuous effect.
4. Dental cone
Minor tablet form that is designed to place in empty
socket following tooth extraction. Main purpose is to
prevent multiplication of bacteria.
7. (c) Tablets administered by other route:
1. Implantation tablet
These are tablets meant for insertion under the skin
2. Vaginal tablet, e.g. Clotrimazole tablet
(D) Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet (Aspirin)
2. Dispensing tablet, e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet
Tablet that dissolves completely in water to form
4. Tablet triturates e.g. Enzyme tablet (Digiplex)
8. Tablet Ingredients (Excipients)
Excipients are substances, other than the active
drug substance or finished dosage form, that have
been appropriately evaluated for safety and are
included in drug delivery systems
They are used in preparations;
To aid in the processing of the drug delivery system
during its manufacturing;
To protect, support, or enhance stability,
bioavailability or patient acceptability;
To assist in product identification;
To enhance any other attribute of the overall safety,
effectiveness, or delivery of the drug during storage8
9. To Impart weight, accuracy, & volume(its allow
acccuracy of dose)
To Improve solubility
To Increase stability
To Enhance bioavailability
To Modify drug release
To Increase patient acceptability
To Facilitate dosage form design
Criteria for tablet excipients;
They must be non-toxic.
They must be commercially available in acceptable
They must be chemically inert.9
10. List of excipients used;
2.)Binder and adhesive
4.) Lubricants and glidants
5.) Colouring agents
6.) Flavoring agents
7.) Sweetening agents
They must be physically and chemically stable.
They must be free from any unacceptable microbiologic
They must be color compatible.
They must have no deleterious effect on the bio-availability
of the drug.
12. 1. Diluents:
Diluents are fillers used to make required
bulk of the tablet when the drug dosage itself is inadequate
to produce the bulk. Secondary reason is to provide better
tablet properties such as improve cohesion, to permit use of
direct compression manufacturing or to promote flow. A
diluent should have following properties:
1. They must be non toxic
2. They must be commercially available in acceptable grade
3. There cost must be low
4. They must be physiologically inert
5. They must be physically & chemically stable by
themselves & in combination with the drugs.
6. They must be free from all microbial contamination.
7. They do not alter the bioavailability of drug.
8. They must be color compatible.
14. 2. Binders and Adhesives:
Binders promote the adhesion of
particles of the formulation.These materials are
added either dry or in wet- form to form granules
or to form cohesive compacts for directly
Example: Acacia, tragacanth- Solution for 10-25%
Cellulose derivatives- Methyl cellulose, Hydroxy
propyl methyl cellulose, Hydroxy propyl cellulose,
Gelatin- 10-20% solution
Glucose- 50% solution
Polyvinylpyrrolidone (PVP)- 2% conc.
Starch paste-10-20% solution
15. 3. Disintegrants:
Added to a tablet formulation to
facilitate its breaking or disintegration when it
contact in water in the GIT.
Example: Starch- 5-20% of tablet weight.
Starch derivative – Primogel and Explotab (1-8%)
Clays- Veegum HV, bentonite 10% level in colored
Cellulose derivatives- Ac- Di-Sol (sodium carboxy
PVP (Polyvinylpyrrolidone), cross-linked
16. 4. Lubricants and Glidants:
Lubricants are intended to
prevent adhesion of the tablet materials to the
surface of dies and punches, reduce inter
particle friction and may improve the rate of flow
of the tablet granulation.
Glidants are intended to
promote flow of granules or powder material by
reducing the friction between the particles.
Example: Lubricants- Stearic acid, Stearic acid salt
-Stearic acid, Magnesium stearate, Talc, PEG
Glidants- Corn Starch – 5-10% conc., Talc-5%
Silica derivative - Colloidal silicas such as Cab-
OSil, Syloid, Aerosil in 0.25-3% conc.16
17. 5. Coloring agent:
The use of colors and dyes in a tablet
has three purposes:
(1) Masking of color 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 &C and D & C dyes. These dyes are applied as
solution in the granulating agent or Lake form of these
(Lakes are dyes absorbed on hydrous oxide and
employed as dry powder coloring.)
Example: FD & C yellow 6-sunset yellow,FD & C yellow
Tartrazine ,FD & C green 3- Fast Green,FD & C blue 1-
Brilliant Blue ,FD & C blue 2 - Indigo carmine
18. 6. Flavoring agents: For chewable tablet flavor
oil are used
7. Sweetening agents: For chewable tablets:
Saccharine (artificial): 500 time’s sweeter than
Disadvantage: Bitter aftertaste and carcinogenic
Disadvantage: Lack of stability in presence of
19. Granulation techniques:
In the pharmaceutical industry, granulation refers to
the act or process in which primary powder particles
are made to adhere to form larger, multi-particle
entities called granules.
1. Dry granulation:
The dry granulation process is used to form granules
without using a liquid solution because the product to
be granulated may be sensitive to moisture and
Forming granules without moisture requires
compacting and densifying the powders.
In this process the primary powder particles are
aggregated under high pressure.19
20. Dry granulation can be conducted under two
processes; either a large tablet (slug) is produced in
a heavy duty tablet press or the powder is squeezed
between two rollers to produce a sheet of materials
(roller compactor, commonly referred to as a
Avoid exposure of the powder to moisture and heat.
Used for powders of very low bulk density to ↑ their
Tablet disintegration and dissolution may be
retarded due to double lubrication and compaction
21. Steps of Dry Granulation
1. The blend of finely divided powders is forced into
the dies of a large capacity tablet press.
2. Then, compacted by means of flat faced
punches (Compacted masses are called slugs
and the process is slugging) or roll compactor to
produce sticks or sheets.
3. Slugs or sheets are then milled/screened to
produce granules(flow more than the original
22. Methods of Dry Granulation
A. Slugging technique
If a tablet press is used for the compaction process,
the term slugging is used. But since particles with a
small particle size do not flow well into the die of a
tablet press, the results are weight differences from
one tablet (slug) to another.
This in turn causes large fluctuations in the forces
applied onto the individual slugs,with translates in
variations of the slug’s mechanical strength.
Therefore, the properties of these granulates
obtained by milling the slugs cannot be controlled
well either. This is one of the main reasons why
slugging is hardly used any more as a dry granulation
23. B. Roller compaction technique
A Roller compactor generally consist of three major
A feeding system, which conveys the powder to
the compaction area between the rolls
A compaction unit, where powder is compacted
between two counter rotating rolls to a ribbon by
applying a force
A size reduction unit, for milling the ribbons to
the desired particle size.
24. Wet granulation:
Wet granulation is a process of using a solution
binder to the powder mixture.
The amount of liquid can be properly managed;
Over-wetting = the granules to be too hard,
Under-wetting =too soft and friable.
Aqueous solutions are safer than other solvents.
Steps involved in wet granulation:
1) Mixing of the drugs and excipients
2) Preparation of binder solution
3) Mixing of binder solution with powder mixture to
form wet mass
4) Coarse screening of wet mass using suitable sieve
25. 5) Drying of moist granules.
6) Screening of granulea through suitable sieve.
7) Mixing of screened granules with disintegrant,
glidant and lubricant.
Limitations of wet granulation:
Multiple separate steps are involved.
Not suitable for heat and moisture sensitive drugs
26. List of equipment used for wet
A) High Shear granulation:
Little ford Lodgie granulator
Little ford MGT granulator
B) Granulator with drying facility:
i) Fluidized bed granulator
ii) Day nauta mixer processor
iii) Double cone or twin shell processor
iv) Topo granulator
C) Special granulator:
i) Roto granulator
27. Special wet granulation techniques:
A) High shear mixture granulation:
Widely used in pharmaceutical industries.
Blending and wet massing accompanied by high
mechanical agitation by an impeler and a chopper
Mixing achieved through shear and compaction
1. Short proccesing time
2. Less amount of binder required
3. Highly cohesive material can be granulated
B) Fluid bed granulation:
Fluid bed granulation is process by which granules
are produced in a single equipment by spraying a
binder solution onto fluidized powder bed
1. The material processed by FBG are finer, free
flowing and homogeneous.
C) Extrusion and spheronization:
It is multiple step process capable of making
uniform sized spherical particles.
1. Applicable for both immediate and controlled
releases dosage form
D) Spray drying granulation:
It is special techniques that directly convert liquids
in to solid (dry powder) in single step and removes
1. Rapid process
2. Ability to be operated continuosly
3. Suitable for heat sensitive products
30. Physics of tablet making:
It is the ability of a powder to decrease the volume
Compression of a powder means reduction in bulk
volume of material as a result of displacement of
gaseous phase under pressure.
It is general term used to describe situation in which
powder material is subjected to some level of
The physics of compaction may be simply stated
as the compression and consolidation of two
phase systems due to applied force.
It is an increase of material resulting particle particle
During tablet manufacturing the compressional
process is followed by a decompression stage in
which applied force is removed to eject the tablet
from the die.
It is referred to as change of geometry of a solid
when it is subjected to opposing forces.
32. Process of compression:
Deformation at the point of contact
Fragmentation and deformation
Deformation of the solid body
33. Tablet processing problems &
1. Binding in the die
6. Excessive weight variation
7. Fissured or pitted surface
8. Soft tablets
9. Protracted disintegration
10. Mottled tablets
11. Drug instability
12. Variation of medicament content
34. In-process controls:
IPC are checks that are carried out before the
manufacturing process is completed. This may
include control of equipment and environment
In process material should be tested for identity,
strength, quality and purity.
Objective of in-process control are both quality
control and process control.
35. Evaluation test for tablets:
Percentage of medicament(assay)
36. Mouth dissolving tablets (MDT):
These are the dosage forms that
rapidly disintegrate and/or dissolve to release
medicament as soon as they come in contact
Fast melting tablets
Fast dissolving tablets (FDT)
Oral disintegrating tablets (ODT)
Oro-dispersible tablets (ODT)
Ease of administration
Convenience of administration
More rapid drug absorption from pre-gastric area
Insufficient mechanical strength
Careful handling required
It may leave unpleasant taste in mouth if not
38. Method of mfg. of MDT:
1) Freeze drying or lyophillization: It is the process
in which water is sublimed from the product after it is
frozen to create amorphous porous structure that can
Active drug is dissolved in aqueous solution
The mixture is done by weight and poured in wells of
preformed blister packs
Trays holding this packs are passed through liq.
Nitrogen freezing tunnel to froze the drug solution
Frozen blisters are placed in refrigerated cabinets
After freeze drying the aluminum foil packing is
Disadvantages: a) time consuming b) expensive c)
2) Tablet molding:
a) Solvent method:
Moistening the powder blend with hydro-alcoholic
Compression at low pressure in molded plates to
form wetted mass.
The solvent is then removed by air drying.
b) Heat method:
Preparations of suspension that contains drug,
agar and sugar
Suspension is poured in blister packaging wells
Solidifying the agar at room temperature to form
Drying is done at 30ºC under vacuum.
Compared to Lyophilization tablets produced are
easy to scale up for industrial manufacture.
3) Spray drying:
In this process,
o Gelatin is used as supporting agent and matrix
o Mannitol as bulking agent
o Sodium starch glycolate (SSG) as
• All these products are used in spray dried form for
• Tablets manufactured by the spray drying technique
have been reported to disintegrate in less than 20
To generate porous matrix volatile ingredients are
incorporated in the formulation and subjected to
Highly volatile substances like ammonium
bicarbonate, ammonium carbonate, benzoic acid,
camphor, naphthalene, urea, phthalic anhydride
may be compressed along with other excipients.
This volatile material is removed by sublimation.
• Tablets manufactured by the spray drying technique
have been reported to disintegrate in 10-20 sec.
5) Direct compression:
It is the most cost effective and simplest
manufacturing technique. This technique is applied
for MDT because of availability of superdisintegrants
and sugar based excipients.
6) Mass extrusion:
This technology involves softening the active blend
using solvent mixture of water soluble PEG and
Then subsequent expulsion of softened mass
through extruder to get cylinder of the product in to
43. Evaluation of MDTs:
1) Weight variation
4) Wetting time
5) In Vitro drug release
6) Crushing strength
8) Modified disintegration
9) Disintegration in oral
10) Water absorption
11) In Vitro dispersion
44. Buccal tablets:
Buccal region offers an attractive route of
administration for controlled systemic drug delivery.
Buccal delivery is the administration of drugs
through the mucosal membrane lining the cheeks.
It is preferred route because buccal mucosa has an
expanse of smooth muscle and relatively immobile
mucosa which makes it a more desirable region for
Direct entry of drug in to systemic circulation
Bypasses first pass metabolism.
Need for the device to maintain its position for many
Smaller area of the tissue available for drug
Low tissue permeability.
Buccal drug delivery system:
They are hydrophilic polymeric matrices that are
capable of swelling when placed in aqueous media.
They swell infinitely and component molecules
dissolve from the surface of matrix.
Then drug release occurs through the spaces or
channels within the network.
Commonly employed dosage form.
Unlike conventional tablets they don't contain
disintegrating agent and tend to remain intact
during the drug release period.
Generally it contains two layers one is drug
containing matrix layer and second is impermeable
It is monoconvex, tablet like mucoadhesive buccal
Striant adheres to gum tissue above the incisors
with the flat surface facing the cheek mucosa.
The active ingredient in striant is testosterone and
insertion of striant is done twice a day.
These are patches designed either as matrix
controlled or membrane controlled devices.
They are preferred over buccal tablets because of
their flexibility and comfort.
50. Evaluation of buccal tablets:
In vitro dissolution
In vitro diffusion/permeability study
In vitro diffusion/permeability study:
The in vitro buccal drug permeation study is carried
out through sheep buccal mucosa using at
37±0.2ºC, mucosa mounted between the donor and
The buccal tablet is placed with the core facing the
membrane and the compartments clamped
The donor and receptor compartments were filled
with phosphate buffer pH 6.4 and the
hydrodynamics in the receptor compartment is
maintained by stirring with a magnetic bead at 50
1ml sample is withdrawn at predetermined time
intervals and analyzed for drug content using UV
The cumulative amount of permeated drug was
plotted versus time and the steady state flux was
calculated using the formula:
ΔM is the amount of drug transported across the
Δt is time and A is the diffusional area.
The swelling rate of the tablet is evaluated by using
pH 6.4 phosphate buffer.
The initial weight of tablet is determined (W1).
Then tablet is placed in pH 6.4 phosphate buffer (6
ml) in a petridish placed in an incubator at 37 ± 1ºC
and the tablet is removed at different time intervals
(0.5, 1, 2, 3, 4, 5, 6, 7, 8 hr), blotted with filter paper
% Swelling index = [(W2-W1)/W1] x100
The surface pH of the tablets is determined in order
to investigate the possibility of any side effects on
the oral cavity.
As acidic or alkaline pH is found to cause irritation
to the buccal mucosa, hence an attempt has been
made to keep the surface pH close to the neutral
A combined glass electrode is used for this
purpose. Buccoadhesive tablets are left to swell for
2 hr on the surface of 1 ml of distilled water at room
The surface pH is measured by means of electrode
by bringing it in contact with the tablet surface and
allowing to equilibrate for 1 min.
Bio adhesive/mucoadhesive strength:
A modified balance method is used to determining
the ex vivo mucoadhesive strength.
Fresh sheep buccal mucosa is obtained and the
mucosal membrane is separated by removing
underlying fat and loose tissues. The membrane is
washed with distilled water and then with phosphate
buffer (pH 6.4) at 37ºC.
The sheep buccal mucosa is cut into pieces and
washed with phosphate buffer (pH6.4). A piece of
buccal mucosa is tied to glass slide which was fixed
on plank and the plank is assembled with a crown
After hydrating the mucosa with distilled water, the
tablet is brought in contact with the mucosa by
applying little force for minute. After initial contact
the tablet is encircled by a thread which fastened a
light plastic beaker through the crown block.
Then water is dropped in to beaker until the tablet
and sheep mucosa are pulled apart by the gravity of
The beaker containing water is weighed and
minimum detachment force was calculated
This detachment force gives the mucoadhesive
strength of the buccal tablet in grams.
Force of detachment (dynes) = Actual wt for
detachment (gm) × g
Where g= acceleration due to the gravity
58. Floating tablets:
Floating drug delivery systems (FDDS)
They have a bulk density less than gastric fluids and so
remain buoyant (floating) in the stomach without affecting
the gastric emptying rate for a prolonged period of time.
Improved drug absorption, because of increased GRT and
more time spent by the dosage form at its absorption site.
Delivery of drugs for local action in the stomach.
Minimizing the mucosal irritation due to drugs, by drug
releasing slowly at a controlled rate.
Treatment of gastrointestinal disorders such as gastro-
Simple and conventional equipment for manufacture.
Floating systems require high level of fluid in the
stomach for the delivery system to float and work
These systems also require the presence of food to
delay their gastric emptying.
There are limitations to the applicability of floating
system for drugs that have solubility or stability
problem in the highly acidic gastric environment or
that are irritants to the gastric mucosa.
Drugs such as nifedipine as well as isosorbide
dinitrate, which are well absorbed along the entire
GI tract and undergoes significant first pass
metabolism may not be desirable candidate since
the slow gastric emptying may lead to reduced
60. Factors controlling gastric retention time of
Density of Dosage Form:
Dosage forms having density lower than that of the
gastric fluids experience the floating behavior and
hence the gastric retention. A density of <1.0 gm/ml is
required to exhibit the floating property.
Size of the Dosage Form:
The mean gastric residence times of the non-floating
dosage forms are highly variable and greatly
dependent on their size. In most cases, the larger the
size of the dosage form, the greater will be the
gastric retention time, because the larger size would
not allow the dosage form to quickly pass through the
pyloric antrum into the intestine.
Food Intake and Nature of the Food
Food intake, the nature of the food, caloric content,
and frequency of feeding have profound effect on
the gastric retention of the dosage form.
Usually the presence of food increases the GRT
(Gastric retention time) of the dosage form and
increases drug absorption by allowing it to stay at
the absorption site for a longer time.
Food containing high calorific value and certain
foodstuffs, especially fats, appear to have an
inhibitory effect on gastric emptying.
Approaches for FDDS
Hydrodynamically balanced systems (HBS)
63. Hydro-dynamically balanced
These are single-unit dosage forms, containing
one or more gel-forming hydrophilic polymers.
The formulation method includes a simple
approach of thoroughly mixing the drug and the
After oral administration this dosage form swells
in contact with gastric fluids and attains a bulk
density of < 1. The air entrapped within the
swollen matrix imparts buoyancy to the dosage
The so formed swollen gel-like structure acts as a
reservoir and allows sustained release of drug
through the gelatinous mass.
Figure shows the HBS by mixing the polymer with
drug and usually administered in a gelatin
capsule. The capsule rapidly dissolves in the
gastric fluid then hydration and swelling of the
surface polymers produces a floating mass.
Drug release is controlled by the formation of a
hydrated boundary at the surface. Continuous
erosion of the surface allows water penetration to
the inner layers, maintaining surface hydration
65. Gas generating system:
These buoyant systems utilise matrices prepared with
swellable polymers (methocel), polysaccharides
(chitosan), effervescent components like sodium
bicarbonate, citric acid and tartaric acid or chambers
containing a liquid that gasifies at body temperature
In single unit systems, effervescent
substances are incorporated in the
hydrophilic polymer, and CO2 bubbles
are trapped in the swollen matrix. (Fig. a)
Bilayer or multilayer systems have
also been designed. Drug and
excipients can be formulated
independently and the gas generating
unit can be incorporated into any of the
layers. (Fig. b,c)
66. Raft forming system:
The mechanism involved in this system includes
the formation of a viscous cohesive gel in contact
with gastric fluids, wherein each portion of the
liquid swells, forming a continuous layer called a
raft. This raft floats on gastric fluids because of
low bulk density created by the formation of CO2
Raft-forming systems have received much
attention for the delivery of antacids and drug
delivery for gastrointestinal infections and
Because raft-forming systems produce a layer on
the top of gastric fluids, they are often used for
gastroesophageal reflux treatment.
67. Low density system:
Low-density systems have density less than 1 g/cm3
with immediate buoyancy.
They are made from low-density materials,
entrapping oil or air.
Polycarbonate, Eudragit S, cellulose acetate,
calcium alginate, agar and low methoxylated pectin
are commonly used as polymers.
The single unit, floating system, consisting of low-
density polypropylene foam powder, matrix-forming
polymers (HPMC, polyacrylates, sodium alginate,
corn starch, carrageenan, agar, guar gum, arabic
gum), drug and filler.
68. Matrix tablets:
These are the formulations in which drug is
uniformly dissolved or dispersed in release
Such devices can be formulated as conventional
or bi-tri layered matrix systems.
1) Hydrophilic matrix:
The release retarding material is water
swellable or swellable erodible hydrocolloid
such as high mol. wt HPMC, HPC, xanthan
gum, sodium alginate, guar gum and cross
linked polymers of acrylic acid.
Hydrophilic matrices are porous systems.
Depending upon the behavior of hydrophilic
polymer two types of matrices are possible;
Free swelling matrix
2) Hydrophobic matrix:
In this matrix release retarding material is used that is
i) slowly soluble, erodible or digestible e.g. waxes
such as cetyl alcohol etc.
ii) Insoluble or non-digestible e.g. EC,
Depending upon the method of incorporation of
drug into matrix hydrophobic matrices further
classified as porous and non-porous matrix..
i) Porous matrix:
This matrix is one where drug and matrix is
simply mixed and compressed into tablets or the
drug dispersed in the polymer solution followed by
ii) Non porous matrix:
This matrix is one where matrix material is first
melted and then drug is incorporated in it through
mixing followed by congealing the mass with
Two types of non porous system is possible;
a) Dissolved drug non porous system
b) Dispersed drug non porous system
Note: Evaluation parameters as per conventional