Tablet Unit 1FINAL.pptx

TABLET
Delivered By MARIYAMBIBI MANDARAWALA
Assistant Professor
KSP.

According to USP, Tablet is defined as a
compressed solid dosage form containing
medicaments with or without Excipients.
According to the Indian Pharmacopoeia,
Pharmaceutical tablets are solid, flat or
biconvex dishes, unit dosage form, prepared by
compressing a drug or a mixture of drugs, with
or without diluents

From patients stand point:
They are easy to carry, easy to swallow and they are
attractive in appearance.
Unpleasant taste can be masked by sugar coating.
Some of the tablets are divided into halves and quarters
by drawing lines during manufacturing to facilitate
breakage whenever a fractional dose is required.

From the standpoint of manufacturer:
•An accurate amount of medicament, even if very small, can be
incorporated.
•Tablets provide best combined properties of chemical,
mechanical and microbiological stability of all the oral dosage
forms.
•Since they are generally produced on a large scale, therefore,
their cost of production is relatively low, hence economical.
•They are in general the easiest and cheapest to package and
ship among all oral dosage forms.
•Some specialized tablets may be prepared for modified
release profile of the drug.
•Product identification is potentially the simplest and cheapest
requiring no additional processing steps when employing an
embossed or monogrammed punch face.

Disadvantages of tablet dosage form
•Difficult to swallow in case of children and unconscious
patients.
•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 offer the best and
lowest cost.
•Some drugs resist compression into dense compacts, owing
to amorphous nature, low density character.

(a) Tablets ingested orally:
Compressed tablets
Multiple compressed tablets
Enteric coated tablets
Sugar coated tablets
Film coated tablets
Chewable tablets
(b) Tablets used in the oral cavities:
Buccal Tablets
Sublingual tablets
Lozenges
Dental cones
(c) Tablets administered by other routes:
Implantation tablets
Vaginal tablets
(d) Tablets used to prepare solutions:
Effervescent tablets
Dispensing tablets
Hypodermic tablets
Tablet triturates
Types of Tablets-

• Tablets ingested orally-
– Compressed tablets:-
– 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. Aspirin (Dispirin)
paracetamol tablets (Crocin).

Multiple compressed tablets / Layered
tablets-
 These are compressed tablets made by more than one
compression cycle. Such tablets are prepared by compressing
additional tablet granulation on a previously compressed
granulation. The operation may be repeated to produce
multilayered tablets of two or three layers.
 To avoid incompatibility, the ingredients of the formulation except
the incompatible material are compressed into a tablet and then
incompatible substance along with necessary excipients are
compressed over the previously compressed tablet.

Sustained action tablets:
These are the tablets which after oral administration
release the drug at a desired time and prolong the effect
of the medicament. These tablets when taken orally
release the medicament in a sufficient quantity as and
when required to maintain the maximum effective
concentration of the drug in the blood throughout the
period of treatment.
e.g. Diclofenac SR tablets.

Enteric coated tablets:
These are compressed tablet meant for administration
by swallowing and are designed to by-pass the
stomach and get disintegrated in the intestine only.
These tablets are coated with materials resistant to
acidic pH (like cellulose acetate phthalate, CAP) of the
gastric fluid but get disintegrated in the alkaline pH of
the intestine.

Sugar coated tablets:
These are compressed tablets containing a sugar
coating. Such coatings are done to mask the bitter and
unpleasant odour and the taste of the medicament. The
sugar coating makes the tablet elegant and it also
safeguard the drug from atmospheric effects.

Film coated tablets:
The compressed tablets having a film coating of some
polymer substance, such as hydroxyl propyl cellulose,
hydroxyl propyl methyl cellulose and ethyl cellulose.
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 than that of sugar coated tablets.

Chewable tablets:
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.
These tablets should have very acceptable taste and
flavour.
Ex- Antacid tablets (Digiene).

Tablets used in oral cavity
1) Buccal tablets:
These tablets are to be placed in the side of the
cheek (buccal pouch) where they dissolve or
erode slowly and are absorbed directly in the
buccal cavity without passing into the alimentary
canal.
Therefore, they are formulated and compressed
with sufficient pressure to give a hard tablets.
e.g. Progesterone tablets.

Sublingual tablets:
These tablets are to be placed under the tongue
where they dissolve or disintegrate quickly and are
absorbed directly without passing into GIT.
e.g. tablets of nitroglycerin, isoproterenol
hydrochloride or erythrityl tetranitrate.

Lozenges tablets:
These tablets are designed to exert a local effect in
the mouth or throat. These tablets are commonly
used to treat sore throat to control coughing in
common cold. They may contain local anaesthetics,
antiseptics, antibacterial agents and astringents.
These are prepared by compression at a high
pressure by the moulding process and generally
contain a sweetening agent, flavouring agent and a
substance which produces a cooling effect.
e.g. Vicks lozenges, Strepsils.

Dental cones:
These are compressed tablets meant for placement in the
empty sockets after tooth extraction. They prevent the
multiplication of bacteria in the socket following such
extraction by using slow-releasing antibacterial
compounds or to reduce bleeding by containing the
astringent.

These tablets contain an excipient like lactose, sodium
bicarbonate and sodium chloride. These cones generally
get dissolved in 20 to 40 minutes time.


Tablets administered by other routes
Implantation Tablets:
 These tablets are placed under the skin or inserted subcutaneously by
means of minor surgical operation and are slowly absorbed. These may
be made by heavy compression but are normally made by fusion. The
implants must be sterile and should be packed individually in sterile
condition. Implants are mainly used for the administration of hormones
such as testosterone steroids for contraception. These tablets are very
usefully exploited for birth control purpose in human beings.
 The disadvantages of implant tablets are their administration, changing
rate of release with change of surface area and possibility of tissue
reactions.

Vaginal tablets:
These tablets are meant to dissolve slowly in the
vaginal cavity. The tablets are typically ovoid or pear
shaped for the ease of insertion. these tablets are
used to release steroids or antimicrobial agents. the
tablets are often buffered to promote a pH favorable to
the action of a specified antimicrobial agent. The
contains easily soluble components like lactose or
sodium bicarbonate.

(d)Tablets used to prepare solutions
(1)Effervescent tablets:
These tablets along with the active medicament contain
ingredients like sodium bicarbonate, citric acid and
tartaric acid which react in the presence of water
liberating carbon dioxide and producing effervescence
leading to disintegration of the tablet, thus fastens
solution formation and increase the palatability.
Eg. Histac (Ranitidine)

Dispensing tablets:
These tablets provide a convenient quantity of potent
drug that can be readily convert into powders and
incorporate into liquids, thus circumventing the
necessity to weigh small quantities. these tablets are
supplied primarily as a convenience for
extemporaneous compounding and should never be
dispensed as dosage form.
e.g. The drugs commonly incorporated are mild silver
potentiate, bichloride of mercury merbromin an
quarternary ammonium compounds.

Hypodermic tablets:
Hypodermic tablets are soft, readily soluble tablets
and originally were used for the preparation of
solutions to be injected.
These tablets are dissolved in sterile water or water
for injection and administered by parenteral route.
these tablets are not preferred now-a-days because
the resulting solution is not always sterile.

Tablet triturates (Moulded tablets):
 These are powders moulded into tablets. They are flat, circular
discs, usually containing a potent substance mixed with lactose,
lactose and sucrose, dextrose, or other suitable diluent.
 Since they are intended to disintegrate very quickly in contact
with moisture, water insoluble adjuncts are avoided. The name
‘tablet triturate’ is appropriate because they usually contain
triturations (trituration = dilution with an inert substance).

Tablets and capsules Ingredients/
Excipients-
In addition to active ingredients, tablet contains a
number of inert materials known as additives or
excipients.
Different excipients are:
Diluent / Filler
Binder and adhesive
Disintegrants
Lubricants and glidants
Colouring agents
Flavoring agents
Sweetening agents

Function of excipients-
Impart weight, accuracy, & volume
Improve solubility
Increase stability
Enhance bioavailability
Modifying drug release
Assist product identification
Increase patient acceptability
Facilitate dosage form design

 Definition- 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:
 They must be non-toxic and low cost.
 They must be commercially available in acceptable grade
 They must be physiologically inert, physically & chemically stable by
themselves & in combination with the drugs.
 They must be free from all microbial contamination.
 They do not alter the bioavailability of drug.
 They must be color compatible.

Characteristics of an ideal diluents
 They must be nontoxic and acceptable to the regulatory
agencies in all countries where the product is to be marketed.
 They must be commercially available in an acceptable grade
in all countries where the product is to be manufactured.
 They must be cheap compared to the active ingredients and
must be physiologically inert.
 They must be chemically stable alone and/or in combination
with the drug(s) and/or other tablet components.
 They must be color-compatible (should not produce any off-
color appearance).
 They must have no negative effects on the bioavailability of
the drug(s) in the product

Commonly used tablet diluents-
Commonly used tablet diluents-
1.Lactose-anhydrous and spray dried lactose
2.Directly compressed starch-Sta Rx 1500
3.Hydrolyzed starch-Emdex and Celutab
4.Microcrystalline cellulose-Avicel (PH 101and PH 102)
5.Dibasic calcium phosphate dehydrate
6.Calcium sulphate dihydrate
7.Mannitol and Sorbitol
8.Sucrose- Sugartab, DiPac, Nutab
9.Dextrose

Lactose
Lactose is the most widely used diluent for tablet
formulation. It is obtained in hydrous and
anhydrous form. The anhydrous form, picks up
moisture when exposed to elevated humidity.
Such tablets should be packed in moisture proof
packets or containers. When a wet granulation
method is employed, the hydrous form of
lactose should generally be used.
Two grades of lactoses are commercially
available:
A 60 to 80 mesh – coarse
a 80 to 100 mesh – regular grade

Advantages:
 Lactose has no reaction with most of the drugs, whether in hydrous
or anhydrous form.
 Lactose formulations show good release rates. Their granulations
are readily dried, and the tablet disintegration times of lactose
tablets are not strongly sensitive to variations in tablet hardness.
 It is a low cost diluent.
Disadvantages:
 Lactose reacts with amine drug bases in presence of alkaline
lubricants e.g. metal stearates (e.g. magnesium stearate) and
gradually discolours (dark brown) with time due to the formation of
furaldehyde. This reaction is called Maillard reaction.

Calcium salts ((DCP/TCP)
 Dibasic calcium phosphate dihydrate (or dicalcium orthophosphate)
(DCP) [CaHPO4, 2 H2O], Calcium sulfate dihydrate (CaSO4 , 2H2O).
Advantages:
 Diluents that exist in their common salt form as hydrates, containing appreciable
bound water as water of crystallization. This bound water of calcium sulfate is not
released below 800C. They possess very low concentration of unbound moisture.
Hence, these
 salts are excellent diluents for water-sensitive drugs. It is superior to anhydrous
diluent, which has a moderate to high moisture demand.
Disadvantages:
 Tetracycline products made with calcium phosphate diluent had less than half the
bioavailability of the standard product. Divalent cation (Ca++) form insoluble
complexes and salts with number of amphoteric or acidic functionality antibiotics,
which generally reduces their absorption (which is also why milk should not be
co- administered with these drug).

Spray dried lactose
Advantages:
 It is used for direct compression (containing drug + diluent +
disintegrant + lubricant). In addition to the direct compression
properties, spray dried lactose also has good flow characteristics. It
can usually be combined with as much as 20 to 25% of active
ingredients without losing these advantageous features.
Disadvantages:
 If spray dried lactose is allowed to dry out and the moisture content
falls below the usual 3% level, the material loses some of its direct
compressional characteristics.
 Spray-dried lactose is especially prone to darkening in the presence
of excess moisture, amines, and other compounds owing to Maillard
reactions. Hence, a neutral or acid lubricant should be used.

Starch
Starch may be obtained from corn, wheat or
potatoes and rice. It is occasionally used as a
tablet diluent. USP grade of starch is usually
possesses moisture content between 11 to 14%.
Specially dried types of starch that have a
standard moisture level of 2-4% are available,
but are costly. Use of such starches in wet
granulation is wasteful since their moisture level
increase to 6-8% following moisture exposure.

Directly compressible starches
Sta–Rx 1500– free flowing, directly compressible
starch. It is used as diluent, binder, disintegrant.
Emdex and Celutab – are two hydrolyzed
starches – contains dextrose 90–92% and
maltose 3–5%
free flowing and directly compressible and may
be used in place or mannitol in chewable tablets
because of their sweetness and smooth feeling in
the mouth.

Dextrose (D–Glucose)
Available in two forms: as hydrates and
anhydrous forms.
Dextrose may sometimes be combined in
formulation to replace some of the spray- dried
lactose, which may reduce the tendency of the
resulting tablets to darken.

Mannitol
Advantages
Because of the negative heat of solution (cooling sensation
in the mouth) its slow solubility, and its pleasant feeling in the
mouth, it is widely used in chewable tablets.
It is relatively non-hygroscopic and can be used in vitamin
formulations.
Low calorie content and non-carcinogenic.
Disadvantages
Costly and has poor flow characteristics and usually require
fairly high lubricant level.

Sorbitol
It is an optical isomer of mannitol and is sometimes combined
with mannitol formulations to reduce the diluent cost.
Disadvantages:- It is hygroscopic at humidities above 65%.
Sucrose
Some sucrose based diluents are:
Sugar tab– 90 to 93% sucrose + 7 to 10% invert sugar
Di Pac – 97% sucrose + 3% modified dextrins
Nu Tab– 95% sucrose + 4% invert sugar + small amount of
corn starch + Mg-stearate
Advantages: They are all used for direct compression.
Disadvantages: All are hygroscopic when exposed to elevated
humidity.

Microcrystalline cellulose (MCC)
Trade Name : Avicel – is a directly compression
material
Two grades are available
PH 101 ® powder
PH 102® granules
Advantages: It acts as diluent and disintegrating
agents.

Binders and Adhesive
 Definition- Agents used to impart cohesive qualities to the
powdered material are referred to as binders or granulators.
 Objective of incorporating binders
 They impart a cohesiveness to the tablet formulation (both
direct compression and wet– granulation method) which
insures the tablet remaining intact after compression.
 They improves the free-flowing qualities by the formation of
granules of desired size and hardness.

Characteristics of binder
 Method-I
 Binders are used in dry form in the powder and then moistened with a solvent (of
the binder) to form wet lumps.
 Method-II
 Binders are often added in solution form. It requires lower concentration of binder.
 By Method-I the binder is not as effective in reaching and wetting each of the
particles within the mass of the powder. Each of the particle in a powder blend has
a coating of adsorbed air on its surface, and it is this film of air which must be
penetrated before the powder can be wetted by the binder solution.
 Method-III
 In direct compression method MCC, microcrystalline dextrose, amylose and PVP
are used – those have good flow property and cohesiveness as well.
 It has been postulated that MCC is a special form of cellulose fibril in which
individual crystallites are held together largely by hydrogen bonding. The
disintegration of tablets containing the cellulose occurs by breaking intercrystallite
bonds by the disintegrating medium.

Starch paste
 Corn starch is often used in the concentration of 10–20%.
 Method of preparation:- Corn starch is dispersed in cold purified water to
make a 5 to 10% w/w suspension and then warming in water both with
continuous stirring until a translucent paste is formed.. (Actually
hydrolysis of starch takes place.)
 Liquid glucose:- 50% solution in water is fairly common binding agent.
 Sucrose solution:- 50% to 74% sugar solution is used as binder. They
produce hard but brittle granules. Their cost is low.
 Gelatin solution
 Concentration 10–20% aqueous solution
 Should be prepared freshly and added in warm condition other wise it
will become solid.
 Method of preparation
 The gelatin is dispersed in cold water and allowed to stand until
hydrated. The hydrated mass is warmed in water bath to dissolve.

Cellulosic solutions
HPMC (Hydroxy propyl methyl cellulose)
Soluble in cold water.
Method of preparation: HPMC is dispersed in hot
water, under agitation. The mixture is cooled as
quickly as possible and as low as possible
HEC (Hydroxy ethyl cellulose), HPC (Hydroxy
propyl cellulose) are other successful binders.
PVP(Polyvinylpyrollidone) Used as an aqueous
or alcoholic solution. Concentration 2% and may
vary.

Disintegrants
 Definition:- A disintegrant is a substance to a mixture of substances,
added to tablet to facilitate its breakup or disintegration after
administration in the GIT. The active ingredients must be released from
the tablet matrix as efficiently as possible to allow for its rapid
dissolution.
 Disintegrants can be classified chemically as: Starches, clays,
celluloses, alginates, gums and cross-linked polymers.
 Starch
 Corn starch, potato starch.
 For their disintegrating effect starches are added to the powder
blends in dry state.
 Mode of action:
 Starch has a great affinity for water and swells when moistened, thus
facilitating the rupture of the tablet matrix.
 Others have suggested that the spherical shape of the starch grains
increases the porosity of the tablet, thus promoting capillary action.
 Normally 5% w/w is suggested and for rapid disintegration 10 – 15%
w/w may be taken.

Super disintegrants
 Super disintegrants like Croscarmelose - cross linked cellulose,
Crospovidone - cross linked polyvinyl pyrrolidone and Sodium starch
glycolate- cross linked starch
 Mode of action
 Croscarmelose swells 4 to 8 fold in less than 10 seconds
 Crospovidone acts by wicking or capillary action.
 Sodium starch glycolate swells 7 to 12 folds in less than 30 seconds.
 Other materials
 Methyl cellulose, Agar, Bentonite, Cellulose,
Alginic acid, Guargum, and Carboxymethyl cellulose.
 Sodium lauryl sulfate is a surfactant. It increases the rate of wetting
of the tablet, thus decreases the disintegrating time.

Lubricant and Glidants Objectives:
 Prevents adhesion of the tablet material to the surface of dies and
punches.
 Reduce inter-particular friction, improve the rate of flow of tablet
granulation.
 Facilitate ejection of the tablets from the die cavity.
 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.
 Example: Stearic acid, Stearic acid salt - Stearic acid, Magnesium
stearate, Talc, PEG (Polyethylene glycols), Surfactants.
 Glidants are intended to promote flow of granules or powder material
by reducing the friction between the particles.
 Example: Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative -
Colloidal silicas such as Cab-O- Sil, Syloid, Aerosil in 0.25-3% conc.
 Antiadherents are used for the purpose of reducing the sticking or
adhesion of any of the tablet ingredients or powder to the faces of the
punches or to the die wall.

Coloring agent
Objectives of using colors that
(i) It makes the tablet more esthetic in appearance and
(ii) (ii) Colour helps the manufacturer to identify the
product during its preparation. Colorants are obtained
in two forms dyes and lakes.
Dyes are dissolved in the binding solution prior to the
granulating process. However, during drying their color
may migrate to the surface and may produce mottling of
the tablet. So another approach is to adsorb the dye on
starch or calcium sulfate from its aqueous solution; the
resultant powder is dried and blended with other
ingredients.
Color lakes are dyes which are adsorbed onto a hydrous
oxide of a heavy metal (like aluminium) resulting in an
insoluble form of the dye.

Flavours and Sweeteners
Flavours are usually limited to chewable tablets or other
tablets intended to dissolve in the mouth. Flavour oils are
added to tablet granulations in solvents, are dispersed on
clays and other adsorbents or are emulsified in aqueous
granulating agents (i.e. binder).
 The use of sweeteners is primarily limited to chewable tablets.
 E.g. Sugar
 Mannitol– 72% as sweet as sugar, cooling & mouth filling effect
 Saccharin– Artificial sweetener, 500 times sweeter than sucrose
 Disadvantages (i) it has a bitter after taste and (ii) carcinogenic
 Cyclamate– either alone or with saccharin– it is banned
 Disadvantage – lack of stability in presence of moisture

Manufacturing of Tablets
Manufacture of tablets involves certain well
defined steps: namely:-
Pulverization and mixing.
Granulation.
Compression.
Coating (if required)

Pulverization and mixing-
 In this step the different solid / powder ingredients are reduced to
the same particle size since particles of different sizes will
segregate while mixing.
 Various equipments like Cutter mill, Hammer mill, Roller mill and
Fluid energy mill is required to reduce the large lumps.
 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)
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.
 Percolation Segregation:- air void Ex- Tea & Coffee jar.
 Trajectory Segregation:- kinetic energy Ex- powder heap

(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 avoid
cross- contamination.
 Step-III Mixing Commonly used blenders are:
 Double cone blender
 V – blender
 Ribbon blender
 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:
 Method-I Method-II
 Drug + Diluent Drug + Diluent
 Dry binder is added Binder Solution is added Blended uniformly

 Suitable solvent is added to activate the dry binder
 Blended in a Sigma - mixer or Planetary mixer till properly wet mass is
formed
 Therefore, when
 (i) a small quantity of solvent is permissible, method-I is adopted and

(ii) a large quantity of solvent is required method-II is adopted.
 However, method-II will give more cohesiveness than method-I if the
amount of binder remains constant.
 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
 (i) passage through a hand screen (in small scale production) or,
 (ii) passage through an oscillatory granulator of hammer mill equipped with
screens
 having large perforations (# 6 – 8 mesh screen).
 Purpose (i) Increase particle contact point
 (ii) Increase surface area to facilitate drying.

 Step-VI Drying
 Drying is usually carried out at 600C. 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 make monosize by passing through
mesh screen.
 For drying granules the screen size to be selected depends on the
diameters of the punch. The following sizes are suggested:
 Tablet diameter uptoMesh Size
 3/16 ”# 20
 3.5 / 16 – 5/16” # 16
 5.5/16 – 6.5/16” # 14

7.0/16 or larger # 12

 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.

 (b) Dry Granulation
 Dry granulation is followed in situations where (i) the effective dose
of a drug is too high for direct compaction and (ii) 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.
 Slug:
 Slug may described as poorly formed tablets or, may be described
as compacted mass of powdered material.
 Purpose: To impart cohesiveness to the ingredients, so as to form
tablets of desired properties.
 Method: It is done either by (i) high capacity heavy duty tablet
press
 (ii) Chilsonator roller compactor.

 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. (Aspirin, Vitamin C).
 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.

Direct Compression Method-
1. Milling
2. Weighing
3. Sieving
4. Blending
5. Compression
Advantages:
(i) It is much more quicker than any of the previous process
 Minimum number of steps are required.
 Modified diluents, binders etc. are available in the market which
assure spherical shape of the granules to modify flow property.
However, they are not used extensively.
 If active medicament is less in amount then there will be no problem
but in case of high dose large amount of active ingredient is to be
replaced by specially treated vehicles to improve flow property or
compressibility.
 These specially treated materials are costly.

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 under go deformation-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 quantitive chang 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 with in 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.
 Single station – stamping press Multi- station- Rotary press

Tablet machine out put is regulated by three basic characteristic like:-
No of tooling sets
No of compression station
Rotational speed of press.
Rotary presses are engineered for fast & economical
production of all kind of tablet.
Ex- The monestry nova rotary tablet press.
Gradually modification made in machines by using
hydraulic or pneumatic pressure to control pressure roll
in place of spring for smoother pressure.
Special type machine:-
Fette machine- Chill the compression(For low MP
substance like wax)
Versa press- For multi-layer tablet
Tablet Tooling Set

Its gives definite size, shape of tablet and certain
identification marking.
For this purpose different types of punches are used-
 Flat faced bevel edged.
 Shallow concave (Round / Capsule shaped)
 Standard concave (Round / Capsule shaped)
 Deep concave (Round / Capsule shaped)
 Extra deep.
 Modified ball
 Auxillary Equipment-
 Mechanized feeder: Due to short D Well time (Monestry
granulation feeding device)
Mechanized hopper loading equipment:
Bulk granulation container:
Electronic monitoring device: To maintain fixed force

Tablet Processing Problems and
its remedies-
 Tablet Processing Problems and its remedies-
 An ideal tablet should be free from any visual defect or functional defect.
With the development of technology, the production process had become
more simplified and more mechanized.
 But now the tablet punching machines are all mechanized, the
mechanical feeding of feed from the hopper into the die, electronic
monitoring of the press, but tablet process problem still persist.
 An industrial pharmacist usually encounters number of problems during
manufacturing. Majority of visual defects are due to inadequate quality or
inadequate moisture in the granules ready for compression or due to
faulty machine setting. Functional defects are due to faulty formulation.

 The Imperfections known as: ‘VISUAL DEFECTS’ are either related
to Imperfections in any one or more of the following factors:
 Formulation design
 Tableting process
 Capping
 Lamination
 Process Related
 Cracking
 Chipping
 Visual Defects
 Sticking
 Formulation Related
 Picking
 Binding
 Machine Related
 Double Impression
 Machine

Capping and Lamination
 Capping is the partial or complete separation of the top or bottom crowns of a
tablet from the main body of the tablet.
 Lamination is the separation of tablet into two or more distinct layers. Usually these
problems are apparent immediately after compression, or even hour or days later.

Detection: Subjecting tablets to the friability test is the quickest way to reveal such
problems.
 Reason and Remedies
 a) Reason: Entrapment of excess air in the granules during compression. If the
granules are light and fluffy this type of problems are encountered frequently.
 Remedies: Increasing the density of granules by adding more binder or
changing the solvent of binder.
 Reason: New set of punches and dies are very tightly fitted; i.e. the clearance
is very negligible hence air cannot come out.
 Remedy: In that case punch diameter should be reduced by 0.005” (i.e. 5 thou)
 Reason: Granules should not be completely dried. if over dried or under dried
then capping may take place.
 Remedy: So moisture content should be kept within 1 – 4%.
 Reason: Tooling set used for longer period of time will form claw-shaped curve
on tip of the punch or wear ring in die in compression area – this form capping.
 Remedy: Punches and dies are changed.

Picking and Sticking
 Picking: -When some portion of the surface of the tablet is removed – it is
termed as picking.
 Sticking: - Sticking refers to tablet materials adhering to the die wall.
Serious sticking at ejection cause chipping.
 Causes and Remedies of picking
 Cause: When punch tips have engraving or embossing, usually of
letters B, A, O are difficult to manufacture cleanly. These may produce
picking.
 Remedy:
 Lettering should be designed as large as possible, particularly on punches
of small diameter.
 Plating of the punch faces with chromium produces smooth, non-adherent
face.
 Colloidal Silica (Cab-o-sil) is added as polishing agent that makes the
punch faces smooth; so that material does not cling to them

 Causes and Remedies of Sticking
 Causes: Excessive moisture may be responsible for sticking.
 Remedy: Further drying of the granulation is then required.

During compression heat is generated and
 low m.p. lubricants e.g. stearic acid may produce sticking.
 Remedy: Low melting point lubricant are replaced with high
melting point lubricants (e.g. Poly ethylene glycol)
 Low m.p. substances, either active ingredients or additives may
soften sufficiently form the heat of compression to cause sticking.
 Remedies:
 Dilution of active ingredient with additional high m.p. diluents.
 Increase in the size of tablet.
 If a low m.p. medicament is present in high concentration then
refrigeration of the granules and then compressing may be the order or
using fette compression machine.

Mottling
 Mottling
 Mottling is an unequal distribution of color on a tablet, with light or
dark patches in an otherwise uniform surface.
 Cause: Migration of water soluble dyes to the surface while drying.
 Remedies:
 Change the solvent system and change the binder system
 Reduce the drying temperature
 Grind to a smaller particle size.
 Use lakes instead of water-soluble dyes.

Quality Control Tests for Tablets-
 General appearance: - Size, shape, and thickness: This is important to
facilitate packaging and to decide which tablet compressing machine to use.
 Organoleptic properties: which include color, odor and taste of the tablets.
 Weight uniformity and Content uniformity: The tablet should contain the
correct dose of the drug.
 Dissolution test: Drug should be released from tablet in a controlled and
reproducible way.
 Weight variation, thickness & diameter: The appearance of tablet should be
elegant & its weight, size & appearance should be consistent.
 Hardness & friability: The tablet should show sufficient mechanical strength
to withstand fracture & erosion during manufacture & handling.
 These factors must be controlled during production and verified after
production, hence called In-process control

Official Standards as per I.P.
 Uncoated tablet:
 Uniformity of container content and Content of active ingredient.
 Uniformity of weight and Uniformity of content.
 Disintegration test.
 Enteric coated tablet:
 Dispersible tablet:
 Uniformity of dispersion.
 Soluble tablet:
 Effervescent tablet:
 Disintegration/Dissolution/Dispersion test.

Weight Variation
 This test is based on the fact that, if the weight variation is within the limits
then it can be said that the amount of medicament will uniform
considerably. Conversely, if the weight variation is not in limits then it can
be concluded that the active medicament will ununiform considerably.
 Sources of weight variation
 Weight variation is solely dependent on the poor flow property of granules
and filling of die cavity. Poor flow properties arise from: (a) improper
lubrication, (b) size of granules and
 adjustment of lower punch.
 Weight variation test
 The U.S.P. weight variation test is run by weighing 20 tablets individually,
calculating the average weight, and comparing the individual tablet
weights to the average. The tablets meet the USP test if “not more than 2
tablets are outside the percentage limit and if no tablet differs by more
than 2 times the percentage limit.”

Content Uniformity test
Weight variation test is applicable when the amount of
medicament in the tablet is high.
In potent drug the medicament is less in amount in
comparison to the other excipients. The weight variation may
meet the pharmacopoeial limitation but this will not ensure
the correct variation of potency. hence, in this case the
weight variation test is followed by content uniformity test.
In this test 30 tablets are randomly selected for sample, and
at least 10 of them are assayed individually according to the
official assay method.
9 of the 10 tablets must have potency within ± 15 % of the
labelled drug content. Only 1 tablet may be within ± 25%.
If this condition is not met then the tablets remaining from the
30 must be assayed individually and none may fall outside ±
15% of the labeled content.

Disintegration Test of Tablets
 The time a tablet takes to disintegrate is the disintegration time.
 To test the disintegration time one tablet is placed in each tube, and the basket
rack assembly is positioned in a 1-litre beaker of water, simulated gastric fluid or
simulated intestinal fluid, at 370C±20C, such that the tablet remains 2.5 cm from
the bottom of the beaker.
 A standard motor moves the basket up and down through a distance of 5 to 6 cm
at a frequency of 28 to 32 cpm (cycles per minute).

Dissolution Test
 Disintegration test simply identifies the time required for the tablet to break
up under the condition of the test but it does not ensure the drug release in
the bulk of the fluid.
 Rate of dissolution is directly related to the efficacy of the drug. Rate of
dissolution is a good index for comparing the bioavailability of two tablet
products of the same drug.
Apparatus-I (Basket)
 In general, a single tablet is placed in a small wire mesh basket and
immersed in the dissolution medium (as specified in the monograph)
contained in a 1000 ml flask at 370 ± 0.50C. Generally it is rotated at 50
rpm unless otherwise specified.
Apparatus-2 (Paddle)
 The same equipment is used. Instead of basket a paddle is introduced as
the stirring element. The tablet is allowed to sink at the bottom of the flask
before stirring.
 Limit: A value of t90% (i.e 90% drug release) within 30 minutes is often
considered satisfactory and is an excellent goal since a common dissolution
tolerance in the USP/NF is not less than 75% dissolved in 45 minutes.

Tablet Hardness
 The resistance of the tablet to chipping, abrasion or breakage under
conditions of storage, transportation and handling before usage depends
on its hardness.
 Method:
 A tablet is taken between the 2nd and 3rd finger and pressing it with the
thumb as fulcrum. If the tablet breaks with a “sharp snap”, yet, it does not
break when it falls on the floor – is said to possess proper hardness.
 Instruments used:
 Monsanto Hardness Tester
 Strong Cobb Hardness Tester -Manual mode.
 Pfizer Hardness Tester.
 Erweka Hardness tester. – Automatic.
 Schleuniger Apparatus. – Operates without manual involvement.
 Hardness of a tablet:
 The hardness at which the tablet crushes is the hardness of the tablet.
 Unit of hardness: Kg/sq.in. or lb/ sq.in
 Limit: Generally maximum 5 kg/sq.in. hardness is required.

Friability
 Friability
 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, i.e. the
friability.
 Instrument: Roche Friabilator
 Objective of friability test:
 This apparatus is designed to evaluate the ability of the tablet to
withstand abrasion, in handling, packaging and shipping operation.
 Method: 20 tablets, previously weighed are taken in the plastic
chamber of the laboratory friability tester. In the plastic chamber the
tablets are subjected to abrasion and shock by rotating the plastic
chamber at 25 rpm for 4 mins (i.e. total 100 revolutions). The tablets
are dedusted and reweighed.
 Limit: - For conventional compressed tablet the weight loss should be
within 0.5 to 1.0 %.

Tablets Coating
Reasons Behind Coating of Tablets:
To mask the taste, odour or colour of the drug. Improving
the product appearance, particularly where there are visible
differences in tablet core ingredients from batch to batch.
Provide physical protection, facilitates handling, particularly
in high speed packaging / filling lines.
To provide chemical protection from its surrounding
environment (particularly air, moisture and light).
To control the release of drug from the tablet e.g. sustained
release tablets, repeat action tablets.
To protect the drug from the gastric environment of the
stomach with an acid resistant enteric coating.

Components Considered in Tablet
Coating
 Tablet Properties: - Shape, Tolerance, Surface area.
 Tablet to be coated must possess the proper physical characteristics like
spherical shape and uniform surface.
 To tolerate attrition of tablets during coating process they must be
resistant to abrasion and chipping.
 As the tablet surfaces that are brittle and soften in presence of heat or
effected by coating composition and tend to become rough in the early
stages of coating process are unacceptable for film coating.
 Coating process: -
 Coating equipment
 Coating parameters.
 Facility & ancillary equipment.
 Automation of coating process.

 Coating composition: - which involves polymers, color, plasticizer, solvent. Types of Coating-
 Sugar Coating.
 Sealing-
 Objectives- (i) To prevent moisture penetration into the tablet core, a seal coat is applied and (ii) To strengthen the tablet
core without a seal coat, the over wetted tablets would absorb excess moisture, leading to tablet softening, and may affect
the physical and chemical stability.
 Ingredients
 Alcoholic solutions of Shellac (10 – 30% solid) or alcoholic solution of zein,
 Alcoholic solution of cellulose acetate phthalate (CAP) or alcoholic solution of polyvinyl acetate phthalate.
 Sub-coating-
 Objectives-To round the edges and build up the tablet size. Sugar coating can increase the tablet weight by 50 to 100% at
this step.
 Method:- The sub-coating step consists of alternately applying a sticky binder solution to the tablets followed by a dusting
of sub-coating powders and then drying. Subsequent coatings are applied in the same manner until the tablet edges have
been covered and the desired thickness is achieved.
 Smoothing (Syruping)-
 Objectives-To cover and fill in the imperfections in the tablet surface caused by the sub- coating step.
 Ingredients-Simple syrup solution (approximately 60–70%(w/w)). Often the smoothing syrups contain a low percentage of
titanium dioxide (1–5%) as an opacifier. This gives a very bright and reflective background for the subsequent coloring
step.
 Color coating-
 Objective-To impart an elegant and uniform colour.
 Ingredient-Syrup (60 – 70% sucrose) containing the desired color.
 Method-Syrup solutions containing the dyes are coated upto 60 individual applications until the desired color is achieved.
After each application of color, the coatings are dried. In the finishing step a few clear coats of syrup may be applied.
 Polishing-
 Objective-To produce the desired luster on the surface of the tablet.

Ingredients-Mixtures of waxes (like beeswax, carnauba wax, candella wax or hard paraffin).
 Method-Either this mixture of waxes is applied as powder or as dispersions in various organic solvents in a polishing pan
(canvas line pan).
 Printing-In order to identify sugar-coated tablets often it is necessary to print them, using pharmaceutical grade ink, by means of a
process of offset rotogravure.

Film Coating
 Film coating adds 2 to 5% to the tablet weight. Film coating is a complex
process that involves the application of thin (in the range of 20-200 μm)
polymer-based coatings to an appropriate substrate (tablets, pellets,
granules, capsules, powders, and crystals) under conditions that permit:
 Balance between (and control of) the coating liquid, addition rate and
drying process.
 Uniformity of distribution of the coating liquid across the surface of product
being coated.
 Optimization of the quality (both visual and functional) of the final coated
product.
 Advantage-
 Substantial reduction in quantity of coating applied (2-4% for film coating,
compared with 50-100% for sugar coating).
 Faster processing times and Improvement in process efficiency and
output.
 Greater flexibility in optimizing formulations as a result of the availability of
a wide range of coating materials and systems.
 Ability to be applied a wide range of pharmaceutical products.

Types
 Pan-pour method-
 Viscous coating materials are directly added from some container into the rotating pan moving with the
tablet bed. Tablets are subjected to alternate solution application, mixing and then drying.
 Disadvantages:
 The method is relatively slow and it relies heavily on the skill of the operator.
 Tablets always require additional drying to remove the latent solvent.
 Aqueous film coating is not suitable for this method because localized over wetting will produce
physicochemical instability.
 Pan-spray method-
 Coating material is sprayed over the tablet bed from nozzles and hot air is passed through the tablet bed
to dry it. The variables to be controlled is pan-spray film coating process are:
 Pan variables:
 Uniform mixing is essential to deposit the same quantity of film on each tablet.
 1. Pan design or baffling: Some tablet shapes mixes freely while other shapes may require a specific
baffling arrangement to ensure adequate mixing.
 Disadvantages: Baffles may produce chipping and breakage if not selected properly.
 Pan speed
 Pan speed affects mixing and the velocity at which the tablet pass under the spray.
 Too slow speed cause localized over-wetting resulting in tablets sticking to each other or to the pan.
 Too high speeds may not allow enough time for drying before the same tablets are reintroduced to the spray.
This results in a rough coating appearance on the tablets.
 Optimum pan speed: 10 – 15 rpm for nonaqueous film coating.
 3 – 10 rpm for aqueous film coating

Fluidized bed process (air
suspension coating)
 Fluidized bed process (air suspension coating)
 This process have been successfully used for rapid coating of tablets, granules and capsules.
 Process variables are as follows: (a) Chamber design and air flow rate controls the fluidization pattern, (b) Tablet
shape, size and density, (c) Volume and rate of air flow either too high rate produce attrition and breakage of tablets
or too low rate ® mass does not move fast enough through the spray region ® over-wetting occurs and (d) Inlet and
exhaust air temperature.
 Examples-
 Non-enteric materials: e.g. Hydroxypropyl methylcellulose (HPMC), Methyl hydroxy ethyl cellulose (MHEC), Ethyl
cellulose (EC), Polyvinyl pyrrolidone (PVP), Sodium carboxymethyl cellulose (Sod. CMC), Polyethylene glycols
(PEG), Acrylate polymers e.g. Eudragit E
 Enteric materials: e.g. Cellulose acetate phthalate (CAP), Acrylate polymers (Eudragit L, S), Hydroxypropyl
methylcellulose phthalate (HPMCP), Polyvinyl acetate phthalate (PVAP).
 Spray variables
 Rate of liquid application.
 Spray pattern.
 Degree of atomization
 These three spray variables are interdependent. For spraying two types of systems are there:
 (a) High-pressure, airless system and (b) low-pressure, air atomization system.

(d) Process air variables (temperature, volume, rate) are required for optimum drying of the coating by evaporation
of the solvent. The balance between the supply and exhaust air flow should be such that all the dust and solvent are
confined within the coating system
 Enteric Coating
 Pan-pour method.
 Pan-spray method.
 Fluidized bed process (air suspension coating)

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