A project report

on

Pharmaceutical Formulations of Tablets

and
Capsules Oral Dosages Forms

VIP Pharmaceuticals Pvt. Limited

Village- Manpura, Tehsil- Nalagarh,
District- Solan, H.P.- 174101

SUBMITTED BY:
Apeksha Garg

GUIDED BY:
Mr. Mohan Verma
(QC/QA Manager, VIP, Solan)

Mr. Ram Awadh

(GM Plant, VIP, Solan)

Hansraj College, University of Delhi

Malkaganj, New Delhi

1
 CERTIFICATE

This is to certify that the project entitled ‘Pharmaceutical

Formulations of Tablets and Capsules Oral Dosages Forms’ is an
authentic record of original work carried out by Apeksha Garg,
student of Hansraj College, University of Delhi carried out during a
period from 01.06.2016 to 15.07.2016 under the supervision of Mr.
Mohan Verma, VIP, Solan and Mr. Ram Awadh, VIP for the partial
fulfilment of degree of B.Sc.(H) Chemistry.

Mr. Mohan Verma Mr. Ram Awadh

QC/QA Manager GM Plant

2
 Acknowledgement
I would like to take this opportunity to express my gratitude towards
all the people who helped in various ways in the successful completion
of my project.

I would like to convey my gratitude to Mr. Mohan Verma for giving

me the constant source of inspiration and help in preparing the project,
personally correcting my work and providing encouragement
throughout the project.

I also thank Mr. Ram Awadh for steering me through the tough as well
as easy phases of the project in a result oriented manner with concern
attention.

Thanking You

Apeksha Garg

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 Index
1. Introduction…………………………………………...…………7-8
1.1 General
1.2 Background

2. Tablets…………………………………………………….....…9-11
2.1 Introduction
2.2 Properties
2.3 Advantages
2.4 Disadvantages

3. Types of Tablets………………………………………...…….12-18
3.1 Tablets ingested orally
3.2 Tablets used in oral cavities
3.3 Tablets administered by other routes
3.4 Tablets used to prepare solutions

4. Capsules………………………………………………...….….19-20
4.1 Introduction
4.2 Advantages
4.3 Disadvantages

5. Types of Capsules…………………………………………….21-22
5.1 Hard Gelatin Capsule
5.2 Soft Gelatin Capsule
5.3 Delayed Release Capsule
5.4 Extended Release Capsule

6. Formulation…………………………………...………………23-24
6.1 Enteral Formulations
6.2 Tablets
6.3 Capsule
6.4 Sustained Release

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7. Manufacturing of Tablets…………………………………….25-29
7.1 Pulverisation and Mixing
7.2 Granulation
7.2.1 Wet Granulation
7.3.2 Dry Granulation
7.3 Direct Compression
7.4 Tablet Coating

8. Problems faced in Tableting………………….……………….30-33

8.1 Problems due to excipient
8.1.1 Picking
8.1.2 Sticking
8.1.3 Mottling
8.2 Problems during process
8.2.1 Capping
8.2.2 Lamination
8.3 Problems due to machines
8.3.1 Double Impression

9. Tablet Coating…………….………………….……………….34-38
9.1 Introduction
9.2 Objective
9.3 Coating Process
9.3.1 Sugar Coating
9.3.2 Film Coating

10. Equipment……………………………...…...……………….39-44
10.1 Rapid Mixer Granulator
10.2 Double Cone Blender
10.3 Strip Packaging Machine
10.4 Tablet Compression Machine

11. Quality control tests…………………………………………45-50

11.1 Official Tests
11.1.1 Weight Variation
11.1.2 Content Uniformity

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 11.1.3 Disintegration Test
11.1.4 Dissolution Test
11.1.5 Friability Test
11.2 Unofficial Test
11.2.1 Tablet Thickness
11.2.2 Tablet Hardness

12. References……………………………………………………….51

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 1.Introduction
1.1 General

Pharmaceutical formulation:
It is the processes in which different chemical substances i.e., active
chemical substances will combine together to produce a medical
compound i.e., medical drug.

There are two types or classifications for pharmaceutical formulation,

these types are the following:

• Oral formulation- The most important characteristic for oral

formulation it must be overcome the problems which associated with
oral administration. The most critical problem is rate of drug solubility
i.e.; the active ingredient of the drug must be soluble in aqueous
solution in a constant rate. This point can be controlled through some
factors like particle size and crystal form. The oral formulation divided
in two parts which are: A- Tablet form & B- Capsule form.

• Topical medication forms- This type includes several parts as the

following: Cream, B- Ointment, C- Gel, D- Paste, and E- Powder.

Dosage Forms:
Dosage forms are pharmaceutical drug products in the form in which
they are marketed for use, with a specific mixture of active ingredients
and inactive components (excipients), in a particular configuration
(such as a capsule shell, for example), and apportioned into a
particular dose.
Dosage forms are the means (or the form) by which drug molecules are
delivered to sites of action within the body.

They are classified into two categories:

• Route of administration: which includes Oral, Topic, Ophthalmic,

Parenteral, Inhalational, Suppository.
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• Physical forms: which includes Solid, Semisolid, Liquid and
Gaseous.

1.2 Background

This process involves production of drug which characterized by two

things: first it must be a stable product; second it must be acceptable to
the patient who will use it. Besides that, in case of synthesis of an oral
medication (tablet or capsule) it will contain a variety of ingredients
besides the drug itself so it is an obligate matter to be sure that all of
these ingredients must be incorporate with each other. Therefore, it is
very important to do a lot of formulation studies in order to detect the
point of incorporation. Besides that, formulation studies must focus on
other factors like particle size, polymorphism, pH and solubility, in
order to check whether these factors will effect on bioavailability of the
drug or not.

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 2.Tablets
2.1 Introduction

Tablets may be defined as the solid unit

dosage form of medicament or
medicaments with or without suitable
diluents and prepared either by
moulding or by compression. It
comprises a mixture of active
substances and excipients, usually in powder form, pressed or
compacted from a powder into a solid dose. They vary in shape and
differ in size and weight, depending on amount of medicinal substance
s and the intended mode of administration.
2.2 Properties

• A tablet should have elegant product identity while free of defects like
chips, cracks, discoloration, and contamination.
• Should have sufficient strength to withstand mechanical shock during
its production, packaging, shipping and dispensing.
• Should have chemical and physical stability to maintain its physical
attributes over time.
• The tablet must be able to release the medicinal agents in a predictable
and reproducible manner.
• Must have a chemical stability over time so as not to follow alteration
of the medicinal agents.

2.3 Advantages

1. Tablets are elegant in appearance and convenient to use.

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2. The tablets dosage form are simple, economical in manufacturing,
most stable and most convenient in packaging, shipping and
transportation.

3.These can be manufactured to show product identification, e.g.

exhibiting the required markings on the surface.

4. A wide range of tablet types is available, offering a range of drug

release rates and durations of clinical effect. Tablets may be formulated
to offer rapid drug release or controlled drug release, the latter reducing
the number of daily doses required (and in so doing increasing patient
compliance).

5. Tablets may be formulated to contain more than one therapeutic

ingredients showing a combination thus reducing multiple tablets use.

6. It is very easy to mask the taste of bitter active ingredients thus make
convenience for patient.

7. Tablets can be formed for local effects e.g. In ulcerative colitis

special tablets can be used for rectal insertion.

8. Tablets provides accurate dosage to the patient

9. Tablets are generally an inexpensive dosage form.

2.4 Disadvantages

1. Its manufacturing involves several unit operation thus at each step

there is loss of ingredients of tablets.

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2. Finding of good compatibility between active and inactive
ingredients for tablets formulation require huge hit and trial
experimentation.

3. The absorption of therapeutic agents from tablets is dependent on

physiological factors, e.g. gastric emptying rate and shows interpatient
variation.

4. May be problematic for children and elders due to difficulties in

swallowing.

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 3.Types of Tablets
Tablets are classified according to their route of administration or
function. The following are the four main classification groups:
(A) Tablets ingested orally:
a. Compressed tables
b. Multiple compressed tables
c. Enteric coated tablets
d. Sugar coated tablets
e. Film coated tablets
f. Chewable tablets
(B) Tablets used in oral cavities:
a. Buccal cavities
b. Sublingual cavities
c. Lozenges
d. Dental Cone
(C) Tablets administered by other routes:
a. Implantation tablets
b. Vaginal tablets
(D) Tablets used to prepare solutions:
a. Effervescent tablets
b. Dispensing tablets
c. Hypodermic tablets
d. Tablet triturates

3.1 Tablets ingested orally

These tablets are designed to be swallowed expect the chewable

tablets. The tablets covered in this category are:

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3.1.1 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 diluent, binders, disintegrates,
lubricants, anti-adherents and in
many cases colorants.

Example: Aspirin, Crocin

3.1.2 Multiple compressed tablets

These are compressed tablets made by more than one compression

cycle.
Example: Diclofenac SR tablets

3.1.3 Enteric coated tablets

These are compressed tablets meant
for administration by swallowing and
are designed to by-pass the stomach
and get disintegrated in the intestine
only.
Example: Tablets containing anthelmintic and amoebicides
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3.1.4 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.

3.1.5 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.
They are generally tasteless.

3.1.6 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. A number of antacid tablets
and multivitamin tablets are prepared as chewable tablets.
Example: Vitamin C chewable tablets (CEILN-(Glaxo))

3.2 Tablets used in oral cavities

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3.2.1 Buccal tablets

These tablets are to be placed in the side of the

cheek where they dissolve or erode slowly and are
absorbed directly in the buccal cavity without
passing into the alimentary canal.

Example: Progesterone tablets

3.2.2 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.
Example: Tablets of Nitro-glycerine

3.2.3 Lozenges tablets

These tablets are designed to exert a
local effect in the mouth or throat. These
tablets are commonly used to treat sore
threat to control coughing in common
cold.
Example: Vicks lozenges

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3.2.4 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.

3.3 Tablets administered by other routes

3.3.1 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 disadvantages of implant
tablets are their administration changing
rate of release with change of surface area and possibility of tissue
reactions.

3.3.2 Vaginal tablets

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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 favourable to the action of a
specified antimicrobial agent. The contains easily soluble components
like lactose or sodium bicarbonate.

3.4 Tablets used to prepare solutions

3.4.1 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 hastens
solution formation and increase the
palatability.

3.4.2 Dispensing tablets

These tablets provide a convenient quantity of
potent drug that can be incorporated readily into
powders and 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.
Example: The drugs commonly incorporated are
mild silver potentiate, dichloride of mercury merbromin a quaternary
ammonium compounds.

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3.4.3 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.

3.4.4 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 trituration (trituration = dilution with an inert
substance).

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 4.Capsules
4.1 Introduction

Capsules are solid dosage forms in which the

drug is enclosed in either hard or soft soluble
container or shells. These shells are usually
formed from gelatin; however, they may
also have made up of starch or other suitable
substances. They are of various shapes and
sizes, and contain a single dose of one or more
active ingredients. They are intended for oral
administration. Capsules are usually intended to be administered orally
by swallowing them whole. Occasionally, capsules may be
administered rectally or vaginally.
In the manufacture of pharmaceuticals, encapsulation refers to a range
of dosage forms—techniques used to enclose medicines—in a
relatively stable shell known as a capsule, allowing them to, for
example, be taken orally or be used as suppositories.

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4.2 Advantages

• Neat and elegant in appearance.

• Enclosing the medication within capsule shells provides a tasteless,
odourless means of administering medication.
• The ready solubility of gelatin at gastric pH provides rapid release of
medication in the stomach.
• Since hard gelatin capsules may be compounded by the pharmacist,
this dosage form offers physician’s greater.
• Flexibility in dosages and drug combinations than is available with
prefabricated medication.

4.3 Disadvantages

• Very soluble salts, such as bromides or iodides should not be

dispensed in capsules, as the rapid release of such materials.
• May cause gastric irritation.
• Capsules are not suitable containers for liquids that dissolve gelatin,
such as aqueous or hydro alcoholic solutions.

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 5.Types of capsules

5.1 Hard Gelatin Capsules

Hard-shell capsules are usually formed from gelatins having relatively

high gel strength. Either type may be used, but blends of pork skin and
bone gelatin are often used to optimize
shell clarity and toughness. Hard-shell
capsules also may be formed from starch
or other suitable substances. Hard-shell
capsules may also contain colorants, such
as D&C and FD&C dyes or the various
iron oxides, opaquing agents such as
titanium dioxide, dispersing agents,
hardening agents such as sucrose, and preservatives. They normally
contain between 10% and 15% water.

Hard-shell capsules typically are filled with powder, beads, or granules.

Inert sugar beads (nonpareils) may be coated with active ingredients
and coating compositions that provide extended-release profiles or
enteric properties. Alternatively, larger-dose active ingredients
themselves may be suitably formed into pellets and then coated.
Semisolids or liquids also may be filled into hard-shell capsules;
however, when the latter are encapsulated, one of the sealing
techniques must be employed to prevent leakage.

5.2 Soft Gelatin Capsules

Soft-shell capsules made from gelatin (sometimes called softgels) or

other suitable material requires
large-scale production methods.
The soft gelatin shell is somewhat
thicker than that of hard-shell
capsules and may be plasticized by
the addition of a polyol such as
sorbitol or glycerine. The ratio of
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dry plasticizer to dry gelatin determines the “hardness” of the shell and
may be varied to accommodate environmental conditions as well as the
nature of the contents. Like hard shells, the shell composition may
include approved dyes and pigments, opaquing agents such as titanium
dioxide, and preservatives. Flavours may be added and up to 5%
sucrose may be included for its sweetness and to produce a chewable
shell. Soft gelatin shells normally contain 6% to 13% water. Soft-shell
capsules also may be printed with a product code, strength, etc. In most
cases, soft-shell capsules are filled with liquid contents. Typically,
active ingredients are dissolved or suspended in a liquid vehicle.
Classically, an oleaginous vehicle such as a vegetable oil was used;
however, non-aqueous, water-miscible liquid vehicles such as the
lower-molecular-weight polyethylene glycols are more common today
due to fewer bioavailability problems.

5.3 Delayed Release Capsules

Capsules may be coated, or, more commonly, encapsulated granules

may be coated to resist releasing the drug in the gastric fluid of the
stomach where a delay is important to alleviate potential problems of
drug inactivation or gastric mucosal irritation. Delayed release means
that there is an enteric coating or capsule that protects the medication
from being destroyed by gastric acids of the stomach to allow the active
ingredient to get to the intestine for proper absorption and functioning.

5.4 Extended Release Capsules

Extended-release capsules are formulated in

such manner as to make the contained
medicament available over an extended period
of time following ingestion. Expressions such
as “prolonged-action,” “repeat-action,” and
“sustained-release” have also been used to
describe such dosage forms.

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 6.Formulations
6.1 Enteral Formulations

Oral drugs are normally taken as tablets or capsules.

The drug (active substance) itself needs to be soluble in aqueous
solution at a controlled rate. Such factors as form can significantly
affect dissolution. Fast dissolution is not always ideal. For example,
slow dissolution rates can prolong the duration of action or avoid initial
high plasma levels. Treatment of active ingredient by special ways
such as spherical crystallization can have some advantages for drug
formulation.

6.2 Tablets

A tablet is usually a compressed preparation that contains:

 5-10% of the drug (active substance);

 80% of fillers, disintegrants, lubricants, and binders; and
 10% of compounds which ensure easy disintegration,
disaggregation and dissolution of the tablet in the stomach or
the intestine.
The dissolution time can be modified for a rapid effect or for sustained
release. Special coatings can make the tablet resistant to the stomach
acids such that it only disintegrates in the duodenum,
jejunum and colon as a result of enzyme action or alkaline ph. Pills can
be coated with sugar, varnish, or wax to disguise the taste.

6.3 Capsule

A capsule is a gelatinous envelope enclosing the active substance.

Capsules can be designed to remain intact for some hours
after ingestion in order to delay absorption. They may also contain a

23
mixture of slow- and fast-release particles to produce rapid and
sustained absorption in the same dose.

6.4 Sustained Release

There are a number of methods by which tablets and capsules can be

modified in order to allow for sustained release of the active compound
as it moves through the digestive tract. One of the most common
methods is to embed the active ingredient in an insoluble porous matrix,
such that the dissolving drug must make its way out of the matrix before
it can be absorbed. In other sustained release formulations, the matrix
swells to form a gel through which the drug exits.
Another method by which sustained release is achieved is through
an osmotic controlled-release oral delivery system, where the active
compound is encased in a water-permeable membrane with a laser
drilled hole at one end. As water passes through the membrane the drug
is pushed out through the hole and into the digestive tract where it can
be absorbed.

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 7.Manufacture of Tablets
In the tablet pressing process, the main guideline is to ensure that the
appropriate amount of active ingredient is in each tablet. Hence, all the
ingredients should be well-mixed. If a sufficiently homogenous mix of
the components cannot be obtained with simple blending processes, the
ingredients must be granulated prior to compression to assure an even
distribution of the active compound in the final tablet. Two basic
techniques are used to granulate powders for compression into a tablet:
wet granulation and dry granulation. Powders that can be mixed well
do not require granulation and can be compressed into tablets through
direct compression.

Manufacture of tablets involves certain well defined steps:

1. Pulverisation and mixing
2. Granulation
3. Compression
4. Coating

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7.1 Pulverisation 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.

7.2 Granulation

Simple powder may not have the desired flow property because there
are many types of forces acting between solid particles:

1. Frictional forces,
2. Surface tension forces,
3. Mechanical forces caused by interlocking of particles of irregular
shapes,
4. Electrostatic forces, and
5. Cohesive or Van der Waals forces

Though bulk density and shape of the particles are important but two
of the most common experiments done to get some idea about the flow
property are:

(i) angle of repose and

(ii) hopper flow rate measurement.

Values for angle of repose ≤ 30° usually indicate a free-flowing

material and Values of angle of repose ≥ 40° suggests a poorly flowing
material.

Hopper flow rates have been used as a method to assess flow ability of
the powder mass. In this method the flow of powder from a conical
hopper is continually monitored by the flow of material out of the
hopper on to a recording balance device.

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7.2.1 Wet Granulation

Wet granulation is a procedure of utilizing a fluid

cover to softly agglomerate the powder blend.
The measure of fluid must be legitimately
controlled, as over-wetting will bring about the
granules to be too hard and under-wetting will
make them be too delicate and friable. Fluid
arrangements have the benefit of being more
secure to manage than dissolvable based
frameworks yet may not be appropriate for
medications which are degraded by hydrolysis.

Procedure

Step 1: Milling of the drug and excipients - Active ingredients,

excipients etc. are milled to obtain a homogeneity in the final
granulation.
Step 2: Weighing - Weighing should be done in clean area with
provision of air flow system.
Step 3: Mixing - Blenders such as Double cone blender, V-Blender,
Ribbon Blender and Planetary mixer are used to mix dry powder mass.
Step 4: Wet Massing - The wet granulate is prepared by adding the
liquid binder–adhesive to the powder blend and mixing thoroughly.
Examples of binders/adhesives include aqueous preparations of corn
starch, natural gums such as acacia, cellulose derivatives such as
methyl cellulose, gelatin, and povidone.
Step 5: Wet Screening - Screening the damp mass through a mesh to
form pellets or granules.
Step 6: Drying - 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. A conventional
tray-dryer or fluid-bed dryer are most commonly used methods.

27
Step 7: Dry Screening - After the granules are dried, they are gone
through a screen of smaller size than the one utilized for the wet mass
to make granules of uniform size.
Step 8: Lubrication - The lubricant is blended very gently using
tumbling action to maintain the uniform granule size.

7.2.2 Dry Granulation

Dry granulation processes create

granules by light compaction of the
powder blend under low pressures. The Roller
compacts so-formed are broken up Compactor
gently to produce granules
(agglomerates). This process is often
used when the product to be granulated
is sensitive to moisture and heat.

The dry granulation process is used to

form granules without using a liquid
solution because the product granulated may be sensitive to moisture
and heat. Forming granules without moisture requires compacting and
densifying the powders. In this process the primary powder particles
are aggregated under high pressure. Swaying granulator or a high-shear
mixer-granulator can be used for the dry granulation.

Dry granulation can be conducted under two processes; either a large

tablet (slug) is produced in a heavy duty tabletting press or the powder
is squeezed between two counter-rotating rollers to produce a
continuous sheet or ribbon of materials

7.3 Direct Compression

Direct compression is a popular choice because it provides the shortest,

most effective and least complex way to produce tablets. The
manufacturer can blend an API with the excipient and the lubricant,

28
followed by compression, which makes the product easy to process. No
additional processing steps are required.

7.4 Tablet Coating

Reasons behind the coating of tablets:

1. To cover the taste, scent or shade of the medication. Enhancing

the item appearance, especially where there are obvious contrasts
in tablet core fixings from batch to batch.
2. Provide physical protection, facilitates handling, particularly in
high speed packaging / filling lines.
3. To provide chemical protection from its surrounding environment
(particularly air, moisture and light).
4. To control the release of drug from the tablet e.g. sustained
release tablets, repeat action tablets.
5. To shield the medication from the gastric environment of the
stomach with a corrosive safe enteric covering.

29
 8.Problems faced in Tableting
Tablet processing problems can be due to the problem in the
formulation or in the compression equipment, or both of them.

8.1 Problems due to excipient

8.1.1 Picking

Picking happens when a part of the tablets

gets sticks to the punch surface and gets
eroded from the tablet surface.

S.No. Cause Remedy

The letters to be embossed should
Due to engraving or
be in large size particularly on small
1. embossing on the upper
punches, or the size of the tablet be
punch
increased.
The punch surface should be coated
2. Rough punch surface with chromium so as to get a
smooth non adherent face of punch.
Colloidal silica may be added in the
3. Sticky surface of tablet formula as polishing agent to avoid
sticking to the punch
4. Too deep dividing lines Reduce the depth of the division.
5. Excess moisture. Proper drying of granules.
Hot granules while The granules are to be dried so that
6.
compression they do not stick.
Reduce the amount or change the
binder so that the adhesive force is
7. Excess binder.
reduced and more cohesive it
becomes.

30
8.1.2 Sticking

It refers to the sticking of the tablet material with the die walls. Due to
this sticking with the die walls, additional force is required to eject the
tablet form the die walls.

S.No. Cause Remedy

1. Low pressure Increase the pressure of punching
Increase the contact time by
2. Fast compression
reducing the speed
Greater concavity of the Reduce the concavity of the punch
3.
punch to optimum level.

8.1.3 Mottling

Mottling is an unequal distribution of

colour on a tablet, with light or dark
patches in an otherwise uniform
surface.

Reason: One cause of mottling may be a coloured drug, whose colour

differs from the colour of excipients used for granulation of a tablet.

S.No. Cause Remedy

A dye may cause mottling
The formulator is intended to
when it migrates to the
1. change the solvent system, binder
surface during the
system, drying temperature.
granulation process
The addition should in the
When coloured binder sequence of First the powder
solution is not evenly colorant is added followed by the
2.
distributed during mixing binder like acacia followed by the
process addition of granulating liquid, and
properly mixed.
A colored active Addition of appropriate colouring
3.
ingredient used along agent.

31
 with colourless
excipients.

8.2 Problems during process

8.2.1 Capping

Capping is the partial or complete

separation of the top or bottom crowns of a
tablet from the main body of the tablet.

Reason: Capping is usually due to the air-

entrapment in a compact during
compression, and subsequent expansion of
tablet on ejection of a tablet from a die.

S.No. Cause Remedy

To remove the excess of fines the
Large number of fines in
1. granulation material should be
the material
passed through 100 to 200 mesh.
2. Improperly dried granules Dry the granules properly.
Inadequate or improper Increase the quantity of binder or
3.
binder use and appropriate one.
Compression may not be
Compress the tablet material at
4. firm due to cool
higher temperature.
temperature
Improper setting of the
Correct height of the lower punch
lower punch, which
5. should be adjusted so that the tablet
causes the sweep off blade
is smoothly ejected out.
to cut the surface

32
8.2.2 Lamination

Lamination is the separation of tablet into

two or more distinct layers.

Reason: Air entrapment during

compression and subsequent release on
ejection

S.No. Cause Remedy

Pre compression step should be
Fast decompression of the included in the process, so that the
1.
tablet pressure at the final compression
is reduces.
Granules may contain Suitable adsorbent or absorbent
2.
oily or waxy material should be added.

8.3 Problems due to machine

8.3.1 Double Impression

It is seen when the tablet punches have engraving or monograms on it

to be embossed on the tablet.

S.No. Cause Remedy

-Use keying in tooling, i.e. insert a

key alongside of the punch, so that it
Free rotation of either
fits the punch and prevents punch
upper punch or lower
1. rotation.
punch during ejection
-Newer presses have anti-turning
of a tablet.
devices, which prevent punch
rotation.

33
 9.Tablet Coating
9.1 Introduction

Tablet coating can be described as a process of applying an edible paint

on the surface of a pharmaceutical dosage form to achieve specific
benefits. This is an additional process in tableting which causes an
increase in the cost of tablet production. Coating can be applied to
several kinds of solid dosage forms like tablets, pellets, pills, drug
crystals, etc. When a coating solution is applied to a batch of tablets in
a coating pan, the surfaces of the tablets get covered with a tacky
polymeric film. The tablets are then allowed to dry and the film
eventually forms a non-sticky dry surface. The coating technique
involves parameters such as the spray pattern, drop size, and nozzle
spacing (in addition to multiple other non-spray related parameters)
which must all be precisely controlled in order to ensure uniform
distribution of the coating material.

9.2 Objective

• To mask the disagreeable odour, colour or taste of the tablet.

• To offer a physical and/or chemical protection to the drug.
• To control and sustain the release of the drug from the dosage form.
• To incorporate another drug which create incompatibility problems.
• To protect an acid-labile drug from the gastric environment.
• Increasing the mechanical strength of the dosage form.

9.3 Coating process

It is most desirable that the coating should be uniform and should not
crack under stress. Hence, various techniques were designed for the
application of the coating on the tablet surface. Generally, the coating
solutions are sprayed onto the uncoated tablets as the tablets are being
agitated in a pan, fluid bed, etc. As the solution is being applied, a thin
film is formed which sticks to each tablet. The liquid portion of the
coating solution is then evaporated by passing air over the surface of
34
the tumbling pans. The coating may be formed either by a single
application or may be developed in layers through the use of multiple
spraying cycles.

Two types of tablet coating are popular –

(i) Sugar coating and

(ii) Film coating

9.3.1 Sugar Coating

Tablet coating developed originally from the use of sugar to mask the
taste and provide an attractive appearance to at the core.

The sugar coating process can be subdivided into six main steps:

1. Sealing: A seal coat is applied over the tablet to prevent moisture

penetration into the tablet core. Shellac was previously used as a
sealant. But due to polymerization problems, it was replaced by
zein (a corn protein derivative).

2. Sub-coating: This step is done to round the edges and increase the
tablet weight. Sugar coating can increase the tablet weight by 50
to 100% at this step.

3. Smoothing: To cover and fill in the imperfections in the tablet

surface caused by the sub-coating step.

4. Colour Coating: To impart an elegant and uniform colour.

5. Polishing: Powdered wax (beeswax or carnauba) is applied to

provide a desired lustre.

6. 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.

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9.3.2 Film Coating

As the sugar coating process is very time consuming and is dependent

on the skills of the coating operator, this technique has been replaced
by film coating technology. The process involves spraying of a solution
of polymer, pigments and plasticizer onto a rotating tablet bed to form
a thin, uniform film on the tablet surface. The choice of polymer mainly
depends on the desired site of drug release (stomach/ intestine), or on
the desired release rate.

Materials used for Film Coating:

1. Film Formers

Criteria:
(a)Solubility requirement for the intended use e.g. free water-solubility,
slow water-solubility or pH -dependent solubility
(b) Capacity to produce an elegant looking product
(c) High stability against heat, light, moisture, air and the substrate
being coated
(d) No inherent colour, taste or odour
(e) High compatibility with other coating solution additives
(f) Nontoxic with no pharmacological activity
(g) High resistance to cracking
(h) Film former should not give bridging or filling of the debossed
tablet
(i) Compatible to printing procedure

Examples:
Non-enteric materials:Hydroxypropyl methylcellulose (HPMC)
Methylhydroxy ethyl cellulose (MHEC)
Ethylcellulose (EC)
Hydroxypropyl cellulose (HPC)
Polyvinyl pyrrolidone (PVP)
Sodium carboxymethyl cellulose (Sod. CMC)
Polyethylene glycols (PEG)

36
 Acrylate polymers e.g. Eudragit E

Enteric materials: Cellulose acetate phthalate (CAP)

Acrylate polymers (Eudragit L, S)
Hydroxypropyl methylcellulose phthalate (HPMCP)
Polyvinyl acetate phthalate (PVAP)

2. Solvents

Criteria:
(a) It should either dissolve or disperse the polymer system.
(b) It should easily disperse other coating solution components into the
solvent system.
(c) Small concentration of polymers (2 to 10%) should not result in an
extremely viscous solution system (> 300 cps), creating process
problems.
(d) It should be colourless, tasteless, odourless, inexpensive, non-toxic,
inert and non-inflammable.
(e) It should have no environmental impact.

3. Plasticizers

As solvent is removed, most polymeric materials tend to pack together

in 3-D honey comb arrangement. "Internal" or "External" plasticizing
technique is used to modify quality of film. Combination of plasticizer
may be used to get desired effect. Concentration of plasticizer is
expressed in relation to the polymer being plasticized. Recommended
levels of plasticizers range from 1-50 % by weight of the film former.
Commonly used plasticizers are castor oil, PG, glycerine, lower
molecular weight (200-400 series), PEG, surfactants, etc. For aqueous
coating PEG and PG are more used while castor oil and spans are
primarily used for organic-solvent based coating solution. External
plasticizer should be soluble in the solvent system used for dissolving
the film former and plasticizer. The plasticizer and the film former must
be at least partially soluble or miscible in each other.

37
4. Colorants

Colourants can be used in solution form or in suspension form. To

achieve proper distribution of suspended colourants in the coating
solution requires the use of the powdered colourants (<10 microns).
Most common colourants in use are certified FD & C or D & C
colourants. These are synthetic dyes or lakes. Lakes are choice for
sugar or film coating as they give reproducible results. Concentration
of colourants in the coating solutions depends on the colour shade
desired, the type of dye, and the concentration of opaquant-extenders.
If very light shade is desired, concentration of less than 0.01 % may be
adequate on the other hand, if a dark colour is desired a concentration
of more than 2.0 % may be required. The inorganic materials (e.g. iron
oxide) and the natural colouring materials (e.g. anthocyanins,
carotenoids, etc.) are also used to prepare coating solution. Magenta red
dye is non absorbable in biologic system and resistant to degradation
in the gastro intestinal track.

5. Opaquant extenders

These are very fine inorganic powder used to provide more pastel
colours and increase film coverage. These inorganic materials provide
white coat or mask colour of the tablet core. Colourants are very
expensive and higher concentration is required. These inorganic
materials are cheap. In presence of these inorganic materials, amount
of colourants required decreases. Most commonly used materials are
titanium dioxide, silicate (talc & aluminium silicates), carbonates
(magnesium carbonates), oxides (magnesium oxide) & hydroxides
(aluminium hydroxides). Pigments were investigated in the production
of opaque films and it was found that they have good hiding power and
film-coated tablets have highlighted intagliations.

6. Miscellaneous coating solution components

Flavours, sweeteners, surfactants, antioxidants, antimicrobials, etc.

may be incorporated into the coating solution.

38
 10.Equipments
10.1 Rapid Mixer Granulator

Rapid mixer granulator is widely used

equipment in pharmaceutical
manufacturing. It is used to mix the
pharmaceutical ingredients and make
the granules before compression.
Impellers and chopper are mainly
responsible for wet granulation in the
rapid mixer granulator.

Impellers: Impellers are fixed at the bottom of the dome shaped

stainless steel bowl. It has two full length and two half-length blades.
These impellers are designed in such a way that small blades lift the
material and full length blades push the material to mix well. These
impellers break up the wet mass into small pieces and granules.
Chopper: These are specially designed small blades located at the
bottom of the dome. It rotates at high speed ﴿2880/1440﴾RPM to give
easy and uniform granulation. Chopper cuts the wet lumps of material
into small sized parts those are mixed equally by the impellers and its
speed is responsible for the size of the granules. Chopper doesn't have
any significant effect on the granule size when impeller speed is high
﴾above 200 RPM﴿.

Principle of Working:

In rapid mixer granulator, formation of granules occurs by rising,

whirling and tumbling motion of material. Dry mixing is done by
adding all ingredients into the RMG by rotation of impeller and
chopper at high speed. During the addition of binder solutions to the
powder impeller and chopper are operated at low speed. After the
formation of wet mass impeller and chopper are operated at high speed
to form the granules of required size.

39
Dry mixing takes about 3‐5 minutes to mix the ingredients; wet mixing
takes 5‐10 minutes to make the wet mass of material while the
granulation process takes 5‐10 minutes to make 0.5 mm to 1.5 mm
sized granules. Mixing time consumed in processing is depends upon
the ingredients quantity and their particle size.

10.2 Double Cone Blender

The Double Cone Blender is an efficient and versatile machine for

mixing dry powder and
granules homogeneously. All
the contact parts are made of
stainless steel. The effective
volume for optimum
homogeneity is between 35-
70% of gross volume. The
SLANT double cone design
eliminates dead sports, which
occasionally occur in
conventional double cone
mixer. It can be used for pharmaceutical, food, chemical and cosmetic
products etc.

Application

(i) Dry powder mixing for tablets and capsule formulations

(ii) Dry granules sub lots mixing to increase the batch size at
bulk lubrication stage of tablet granules.

Salient Features

 The conical shape at both end enables uniform mixing and easy
discharge.
 The cone is statically balanced which protects the gear box and
motor from any excessive load.
 Powder is loaded into the cone through a wide opening and
discharged through a butterf.

40
  Depending on the characteristic of the product, paddle type
baffles can be provided on the shaft for better mixing, uniform
blending and de-agglomeration.
 Contact parts are made of S.S.304 or S.S.316.
 Flame proof electricals can be provided as optional.
 'Slant' design (off centre) CLIN CONE BLENDER.
 Dust free bin charging system ensures minimum material
handling.

10.3 Strip Packaging Machine

Strip Packing Machine is a high speed packing

machine suitable for a variety of products like
tablets, Capsules, draggers etc. High quality
sealing is achieved with features such as
temperature controllers, variable pressure for
sealing rollers and rugged and precision
construction.

Special Features

(i) Available in different models of 2, 4, 6, 8, 10 and 12 Track,

capacity from 400 to 3000 Tab./min. with max. sealing
width of 250 mm.
(ii) Standardised, quickly interchangeable parts.
(iii) Compact steel fabricated body with adequate inspection
windows.
(iv) Adjustable foil cutting and slitting device.
(v) Noiseless, trouble-free smooth operation
(vi) Vibratory feed control for higher output.
(vii) Cavity shape and knurl design of choice.
(viii) Cartridge type heaters and therinostatic temperature control
suitable for all types of packing materials.
(ix) Ensures air tight leak-proof packing.
(x) Suitable for most heat scalable foils like Paper Poly,
Aluminium Poly, Cello Poly, Cellophane, Glassine Poly.

41
10.4 Tablet Compression Machine

Tablet compression machine makes the tablets by

pressing the granules in die with lower and upper
punch. Tablets are being formed by compressing the
granules using the compression machines. Different
innovations to tablet compression machines are
being done to improve the production rates and now
it is possible to produce more than 500,000 tablets
per hour. A tablet formation takes place by the
combined pressing action of two punches and a die.

Principle
The basic principle behind the tablet compression machine is hydraulic
pressure. This pressure is transmitted unreduced through the static
fluid. Any externally applied pressure is transmitted via static fluid to
all the directions in same proportion. It also makes it possible to
multiply the force as needed.

42
Different Stages of Compression Process
The tablet compression procedure that is used in different
pharmaceutical companies is divided into four distinct stages. These
are named as filling, metering, compression and ejection. These all four
steps are explained below:

1. Filling: This procedure of the tablet compression machine involves

transfer of the granules into position for tablet compression. The
ultimate product is then blended for homogeneous blend. Then the
mixture flows to the compressing tool punch‐die cavity. The punch‐die
cavity is made of punch‐die and lower punch. Then the position of
lower punch in the die is responsible for the volume of the cavity. This
volume must be appropriately adjusted for weight of granules to be
compressed to make the tablets.

2. Metering: The metering procedure for the tablet compression

procedure involves removal of excess granules from the compression
machine. At this stage the required weight ﴾volume ﴿of granules to be
compressed into tablets is controlled by the height of the lower punch
in the die and the height of the lower punch is controlled by the
metering cam. The lower punch is raised to the required level in the die
to get the required weight of granules in the punch‐die cavity. The
excess granules are scraped from the surface of the die table. The
metering method is similar to the process used to determine the
weight of flour during the making of a cake.

3. Compression: During compression stage the top and bottom

punches come together by pressure within the die to form the tablet. As
the punches enter into the compression stage, the top and bottom
punches move between two large wheels called compression rolls.
These compression rolls push the punches to words the die to form the
product. So, distance between the top and bottom punches determines
the thickness and the hardness of the tablets. When the punches are so
close together, a thin and hard tablet is created.

43
4. Ejection: The ejection procedure for the tablet compression process
involves removal of the tablet from the lower punch‐die station. In this
stage, the
upper punch retracts from the die cavity and rises above the turret table.
Then the lower punch rises in the die, which in turn pushes the tablet
upward to
the top surface of the die table and out of the die cavity. Then by a
scrapper tablets are collected in the container.
There are different types of compression machines are available for
tablet manufacturing and these have their identification on the basis of
the number of
tablet compression stations as 25 station, 35 stations, 55 stations etc.

44
 11.Quality Control Tests
Quality control is concerned with sampling, specifications for raw
material, and finished product, testing, documentation, release product,
analytical methodologies and good laboratory practice.

Specifications for tablets:

1. The tablet should include the correct dose of the drug (Weight
uniformity and content uniformity test).
2. The drug should be released from the tablet in a controlled and
reproducible way (Dissolution test).
3. The tablet should show sufficient mechanical strength to withstand
fracture and erosion during manufacturing and handling (Hardness and
friability test).
4. The appearance of the tablet should be elegant and its weight, size
and appearance should be consistent (Visual observation, weight
variation, thickness and diameter of the tablet).
5. The tablet should be packed in a safe manner.

Two Types of tests:

(A) Official Quality Control Tests:

a. Uniformity of content of active ingredient (Uniformity of
weight & Content uniformity)
b. Disintegration test
c. Dissolution test
d. Friability test

(B) Unofficial Tests:

a. Tablet thickness
b. Tablet hardness

45
11.1 Official Tests

11.1.1 Weight Variation

This test is based on the fact that, if the weight variation is not much
then it can be said that the amount of medicament will not vary
considerably. Conversely, if the weight variation is larger than it can be
concluded that the active medicament will also vary considerably.

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
(c) adjustment of lower punch.

Weight variation test

Weigh 20 tablets individually (i.e. determine the weight of each

tablet alone; X1, X2, X3… X20)
Calculate the average weight of tablets (X) = (X1+X2 +X3+…+
X20)/20

Limits according to USP

 Weight of tablet 130 mg or less than
% error = ±10%
 Weight of tablet 130-324 mg or less than

46
 % error = ±7.5%
 Weight of tablet 324 mg or less than
% error = ±5%
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.”

11.1.2 Content Uniformity

USP defines content uniformity test for tablets containing less than
≤25 mg and less than ≤ 25% of tablet weight in case of coated or
uncoated tablets.
● Determining the amount of drug in a sample of tablets (10).
● The average drug content is calculated.
● The content of the individual tablets should fall within specified
limits in terms of % deviation from the mean (85 – 115%). If not
comply, repeat using 20 more tablets. No one should be 75 – 125%
deviation.

11.1.3 Disintegration Test

The USP device to disintegrate the tablets uses 6 glass tubes that are 3”
long; open at top and 10 mesh screen at the bottom end. To test for
disintegration time, one tablet is placed in each tube and the basket rack

47
is positioned in a 1-L beaker of water, stimulated gastric fluid or
stimulated intestinal fluid at 37 ± 2℃ such that the tablet remains 2.5cm
below the surface of liquid on the upward movement and not closer
than 2.5cm from bottom of the beaker in the downward movement.
Move the basket containing the tablets up and down through a distance
of 5-6 cm at a frequency of 28 to 32 cycles per minute. Floating of the
tablets can be prevented by placing perforating plastic discs on each
tablet.

According to the test, the tablet must disintegrate and all the particles
must pass through the 10 mesh screen in the specified time. If any
residues remain, it must have soft mass.

Disintegration time: Uncoated tablet: 5-30 minutes

Coated tablet: 1-2 hours

11.1.4 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 1: 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 37° ± 0.5℃.
Generally, it is rotated at 50 rpm unless otherwise specified.

48
Apparatus 2: 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 is not less than 75% dissolved in 45
minutes.

11.1.5 Friability Test

Friability of a tablet can determine in laboratory by

Roche friabilator. This consists of a plastic chamber
that revolves at 25 rpm, dropping the tablets through
a distance of six inches in a friabilator, which is then
operate for 100 revolutions. The tablets are
reweighed. Compress tablet that lose less than 0.5
to 1.0 % of the tablet weigh are consider acceptable.

11.2 Unofficial Tests

11.2.1 Tablet Thickness

The thickness of a tablet is only variables. Tablet thickness can be

measured by micrometre or by other device. Tablet thickness should be
controlled within ± 5% variation of standard value.

11.2.2 Tablet Hardness

The hardness at which the tablet crushes is the

hardness of the tablet.

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

49
when it falls on the floor – is said to possess proper hardness.

Unit of hardness: Kg/sq.in. or lb/ sq.in

Limit: Generally maximum 5 kg/sq.in. hardness is required.

50
 10.References
 http://4my3939.blogspot.in/
 http://www.slideshare.net/nitinkadam3/tablets/1
 https://en.wikipedia.org/wiki/Pharmaceutical_formulation
 http://druginfocentre.blogspot.in/2013/02/capsules-capsules-are-
solid-dosageforms.html
 http://faculty.ksu.edu.sa/Diaa/Documents/tablet%20and%20cap
sules.pdf

51