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TABLETS

Solid pharmaceutical dosage forms containing drug


substances with or without suitable diluents and prepared either
by compression or molding methods.

Advantages and disadvantages of tablet as a


dosage form
Advantages
1- Large scale manufacturing. Therefore, economy can be
achieved
2- Accuracy of dose
3- Made release profile can be achieved.
4- Longer expiry period and minimum microbial spillage

5- Not a sterile dosage form


6- Ease of packaging (blister or strip) and easy handling
7- Easy to transport in bulk. Can be carried by patients.
8- Organoleptic properties (taste, appearance and odour) are
best improved by coating of tablet.
9- Product identification is easy and markings done with the help
of grooved punches and printing with edible ink.
10- Different types of tablets are available like buccal, floating,
colon targeting, effervescent, dispersible, soluble, and
chewable, etc.

Disadvantages
1- It is difficult to convert a high dose poorly compressible
drug into a tablet of suitable size for human use.
2- Difficult to formulate a drug with poor wettability, slow
dissolution into a tablet.
3- Slow onset of action as compared to parenterals, liquid
orals and capsules.
4- The amount of liquid drug (e.g. Vitamin E, Simethicone)
that can be trapped into a tablet is very less.
5- Difficult to swallow for kids, terminally ill and geriatric
patients.
6- Patients undergoing radiotherapy cannot swallow tablet.

Tablet classified by route of administration and by the type


of drug delivery system they represent within that route.

A- ORAL TABLETS FOR INGESTION


These tablets are meant to be swallowed intact along with
a sufficient quantity of potable water.
1- Standard compressed tablets
2- Multiple compressed tablets
I. Compression coated tablet
II. Layered tablet
3- Modified Release tablet

4- Delayed action tablet


5- Targeted tablet
I. Floating tablet
II. Colon targeting tablet
6- Chewable tablet
7- Dispersible tablet

B- TABLETS USED IN THE ORAL CAVITY


The tablets under this group are aimed release in oral
cavity or to provide local action in this region.
The tablets under this category avoids first-pass
metabolism,
decomposition in gastric environment and gives rapid
onset of action.

1- Lozenges and troches


2- Sublingual tablet
3- Buccal tablet
4- Dental cones
5- Mouth dissolved tablet

C- TABLETS ADMINISTERED BY OTHER


ROUTES
These tablets are administered by other route except for
the oral cavity.
1- Vaginal tablet
2- Implants

D- TABLETS USED TO PREPARE SOLUTION


The tablets under this category are required to be
dissolved first in water or other solvents before administration
or application.
This solution may be for ingestion or parenteral
application or for topical use depending upon type of
medicament used.
1- Effervescent tablet
2- Hypodermic tablet
3- Soluble tablet

Standard compressed tablet


These tablets are formed by compression and contain
no special coating.

STANDARD COMPRESSED TABLET

1- Sugar-coated Tablets (SCT):


These are compressed tablets containing a sugar
coating. Covering the drug objectionable tastes or odours
Protecting materials sensitive to oxidation.

2. Film-Coated Tablets (FCT)


These are compressed tablets which are covered with
a thin layer or film of a water-soluble material.

Multiple Compressed Tablets (MCT)


These are compressed tablets made by more than one
compression cycle

A- Layered Tablets:
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.

MULTILAYERED TABLET

B- Press-Coated Tablets :
Such tablets, also referred to as dry-coated, are
prepared by feeding previously compressed tablets into a
special tableting machine and compressing another
granulation layer around the preformed tablets.
Used to separate incompatible drug substances
Give an enteric coating to the core tablets.
Both types of multiple-compressed tablets have been
widely used in the design of prolonged-action dosage forms.

COMPRESSION COATED TABLE

Modified release tablet


The main aim
Release the medicament slowly for long time duration
Improvement in patients compliance as the dosage
Reduced frequency
Reduced, side effects and toxicities
The drug release can be modified by providing suitable
micro environmental pH in the tablet e.g., acidic polymer,
succinic acid, etc. Similarly, inclusion of alkaline polymers
results in desirable drug release of acidic drugs.

Matrix technology
Products exhibit first order drug release characteristics.
Its necessary to employ specially designed materials or
strategies to manipulate tablet structure or geometry.
Combination of conventional HPMC matrix technology with
upper and lower layer.

MATRIX TABLET

Release of medicament can follow various


mechanisms
i)Diffusion is rate limiting
Movement of drug molecules occurs from high concentration
in the tablet to lower concentration in gastro intestinal fluids.
This movement depends on
1- surface area exposed to gastric fluid
2- diffusion pathway
3- drug concentration gradient
4- diffusion coefficient of the system

DIFFUSION RELEASE PATTERN

ii)Dissolution is rate limiting


The drugs with poor water solubility are sustained release
forms.
While for water soluble drugs, its possible to incorporate a
water insoluble carrier to reduce dissolution of the drug
particles are coated with this type of materials e.g.
Polyethylene Glycol

iii) Release is controlled by ion exchange


Ion exchangers are water insoluble resinous materials
containing salt forming anionic or cationic groups.
The drug release depends upon high concentration of
charged ions in gastro intestinal tract where, the drug
molecules are exchanged and diffused out of the resin into the
surrounding fluid.
This mechanism relies upon the ionic environment of resin
and not pH or enzyme on absorption site

iv)Osmotic pressure is rate limiting


Osmosis is a phenomenon in which the flow of liquid occurs
from lower concentration to higher concentration through a
semi permeable membrane which allows transfer of liquid only.

OSMOTIC RELEASE
PATTERN

Prolonged-Action Tablets:
Provide medication over a period of time.
The release of the drug substance is prevented for an
interval of time after administration or until certain physiological
conditions exist

Targeted tablet
When we need to release drug at a specific site in the
elementary tract, targeted drug delivery is a preferred option.

I. Gastro retentive Tablet


This type of dosage form is to be opted when drug release
is desired in stomach.
To retain the drug for longer time period in stomach,
following approaches can be used:
1- Low density tablet (effervescent or non effervescent)
2- Tablets that can expand in gastric environment (swelling)
and thus increasing the size so that it cannot cross the pyloric
sphincter.
3- Using mucoadhesive polymers that stick to mucosa of
stomach and provide slow drug release.
Drugs like Diazepam, Levodopa, and Ciprofloxacin are
successfully marketed in this formulation

II. Colonic tablets


When the aim is to deliver the drug into colon without
dilution in other regions of gastrointestinal tract
or the drug has poor absorption in stomach
or small intestine, colonic drug delivery is an answer of
choice.
Mechanisms for drug release in this area
1- Coating with pH sensitive polymer e.g., EudragitS100,
Eudragit L100,
2- Biodegradable polymer like polymers which are sensitive to
colonic bacteria
3- Bioadhesive polymers which selectively sticks to colonic
mucosa e.g., polycarbophils

Chewable tablet
The patients who have difficulty in swallowing tablets
whole or for children, chewable tablet serves as an attractive
alternative.
The advantage of this medication is that it can be taken
at any time or when water is not available. e.g Antacid and
multivitamin tablet which a patient can take as a daily dose

Dispersible tablet
These tablets disintegrate either rapidly in water, to form
a stabilized suspension, or disperse instantaneously in the
mouth to be swallowed without the aid of water.
So, its preferred for
Pediatric patients who cannot swallow a solid dosage
form
The drug is unstable if formulated in liquid formulation
Faster onset of action as compared to standard tablet

Lozenges
The tablet is a flat faced at least about 18mm in diameter
and meant to suck and dissolves in the mouth.
Flavors and sweeteners are added to make tablets
palatable.
The tablet generally contains sucrose or lactose and gelatin
solution to impart smooth taste.
Lozenges for local action in mouth/ throat are: antiseptics,
antibiotics, demulcents or multivitamin tablet

Sublingual tablet
They are to be placed under the tongue and produce
immediate systemic effect by enabling the drug absorbed
directly through mucosal lining of the mouth beneath the
tongue.
The absorption avoids first-pass metabolism.
The tablets are usually small and flat
The tablet must dissolve quickly allowing the drug to be
absorbed quickly.
Designed to dissolve in small quantity of saliva.
The patient should avoid eating, drinking, smoking and
possibly talking in order to keep the tablet in place.
Swallowing of saliva should also be avoided since the saliva
may contain dissolved drug

Buccal tablet
- Drug absorption is desired but fast drug absorption is not
intended.
- The tablets are designed not to disintegrate.
- They are flat elliptical or capsules shaped tablets as it can
be easily held between gum and cheek.
- Tablet kept for 30-60 minutes in oral cavity,
- Avoid gritty or irritating sensation.
- Used when replacement hormonal therapy is to be
administered. Antifungal drugs are preferred to be
administered by this route. e.g., Miconazole

Dental cones
These tablets are designed to be loosely packed in the
empty socket remaining following a tooth extraction.

Mouth dissolved tablet


They are also called mouth-dissolving, fast-dissolving,
rapid-melt, porous, orodispersible, quick dissolving.
Preferred when fast action or relief is desired.
Most commonly used drugs under this formulation are the
agents active against migraine.
The tablets are designed to disintegrate as well as dissolve
within one minute or some within 10 seconds of oral
administration in limited quantity of saliva.

Vaginal tablet
This tablet undergoes slow dissolution and drug release in
vaginal cavity of women.
The tablet should be made compatible with plastic tube
inserters which are designed to place the tablet in the upper
region of vaginal tract.
These tablets generally release antibacterial, antiseptics or
astringents to treat vaginal infections or release steroids for
systemic absorption.

Implants
These tablets are inserted into subcutaneous tissue by
surgical procedures where they are very slowly absorbed over
a period of a month or a year.
The diameter not more than 8mm.
They are sterile formulation without excipients and made
hard with large particle size to achieve gradual drug release.

Effervescent tablet
The oral dosage forms are the most popular way of taking
medication despite having some disadvantages like slow
absorption and thus onset of action is prolong.
Drugs have limited level of stability in liquid form.
The tablet is quickly broken apart by internal liberation of
CO2 in water due to interaction between tartaric acid and citric
acid with alkali metal carbonates or bicarbonates in presence of
water.

Hypodermic tablet
These tablets contain one or more readily water soluble
ingredients and are intended to be added in water for injection
of sterile water to form a clear solution which is to be injected
parenterally.

Soluble tablet
Water soluble tablets are intended for application after
dissolution in water and contain an active ingredient should be
totally soluble in water at used concentrations.
All the excipients used to formulate these tablets are
required to be completely soluble in water including the
glidants, binders, etc.

Molded Tablets or Tablet Triturates


Tablet triturates are usually made from moist material
using triturate mold which gives them the shape of cut
sections of a cylinder. Such tablets must be completely and
rapidly soluble.

Dispensing Tablets
These tablets provide a convenient and quantity of
potent drug that can be incorporated readily into powders
and liquids

Tablets for solution


Compressed tablets to be used for preparing
solutions or imparting given characteristics to solutions
must be labeled to indicate that they are not to be
swallowed. Examples of these tablets, are Halazone
Tablets for Solution and Potassium Permanganate
Tablets for Solution

COMPRESSED TABLETS
In order for medicinal substances, with or without
diluents, to be made into solid dosage forms with pressure,
using available equipment, it is necessary that the material,
either in crystalline or powdered form, possess a number of
physical characteristics.
These characteristics include
The ability to flow freely,
Cohesiveness,
Lubrication.
Since most materials have none or only some of these
properties
Methods of tablet preparation;
1- Granulation method.
2- Direct compression.

Tablet Ingredients
In addition to the active or therapeutic ingredient, tablets
contain a number of inert materials. The latter are known as
additives.
Classified according to the part they play in the finished tablet.
The first group contains those which help to impart
satisfactory compression characteristics to the formulation.
These include
1- Diluents

2- Binders

3- Lubricants

The second group of added substances helps to give


additional desirable physical characteristics to the finished
tablet. Included in this group are
1- Disintegrators
4- Sweetening agents

2- Colors

3- Flavors

EXCIPIENT WITH THEIR FUNCTIONS IN TABLET FORMULATION

EXCIPIENT

FUNCTION

Diluents

Diluents make the required bulk of the tablet when


the drug dosage itself is inadequate to produce
tablets of adequate weight and size.

Binders

Binders are added to tablet formulations to add


cohesiveness to powders, thus providing the
necessary bonding to form granules, which under
compaction form a cohesive mass or a compact
which is referred to as a tablet.

Lubricants

Lubricants are intended to reduce the friction


during tablet formation in a die and also during
ejection from die cavity.

Disintegrates A disintegrate is added to most tablet formulations


to facilitate a breakup or disintegration of the tablet
when placed in an aqueous environment.

EXCIPIENT
Glidants

FUNCTION
Glidants are intended to promote the flow of tablet
granulation or powder mixture from hopper to the
die cavity by reducing friction between the particles.

Colours Colours are added to tablet formulation for following


purposes: to disappear colour drugs, product
identification and for production of more elegant
product.
Flavours

Flavours are added to tablet formulation in order to


make them palatable enough in case of chewable
tablet by improving the taste.

Adsorbents Adsorbents are capable of retaining large quantities


of liquids without becoming wet; this property of
absorbent allows many oils, fluid extracts and
eutectic melts to be incorporated into tablets.

A. Fillers (Diluents)
Tablet fillers or diluents comprise a heterogeneous group
of substances
Combinations are also a possibility, consideration should
be given to possible mixtures.
Tablet diluents or fillers can be divided into following
categories:
1- Organic materials - Carbohydrate and modified
carbohydrates.
2- Inorganic materials Calcium phosphates and others.
3- Co-processed Diluents.
Carbohydrate substances such as sugars, starches and
celluloses may also function as binders during wet granulation
process.
The inorganic diluents, do not exhibit binding properties
when used in wet granulation and direct compression.

Tablet diluent or filler may also be classified on the basis of


their solubility in water as soluble and insoluble.

INSOLUBLE TABLET FILLERS OR


DILUENTS

SOLUBLE TABLET FILLERS OR


DILUENTS

Starch
Powdered cellulose
Microcrystalline cellulose
Calcium phosphates, etc.

Lactose
Sucrose
Mannitol
Sorbitol, etc.

Calcium phosphates
They are widely used both as wet granulation and direct
compression diluents in tablet formulation. Bulk density of
calcium phosphates is higher than that of organic fillers.

Characteristic of Calcium Phosphates


1- They are directly compressible and are characterized by
brittle fracture on compression during tableting process.
2- Hard tablets are produced.
3- They exhibit good flow properties.
4- They are non hygroscopic.
5- They are inexpensive.
6- They are abrasive in nature and hence can cause wear
of tablet tooling.
7- Sometimes their alkalinity is a major source of drug
instability.

Microcrystalline cellulose (Avicel)


1- Microcrystalline cellulose (MCC) is highly compressible and
is perhaps the most widely used direct-compression tablet
2- Hard tablets, at low compression pressures
3- It undergoes plastic deformation on compression and hence
it is more sensitive to lubricants.
4- It exhibits fair flowability.
5- It exhibits binding properties.
6- It also possesses disintegrant activity and thus promotes
fast tablet disintegration.

Sucrose
1- It requires high machine pressures, especially in cases
with over wetted granulations.
2- It is water soluble.
3- It possesses good binding properties.
4- It is slightly hygroscopic.
5- It is inexpensive.
6- It produces gritty mouth feel.
7- It is a calorie contributor and is cariogenic.
8- Tend to harden with time
9- Tend to brown with time

Mannitol
1- It exhibits poor flow properties.
2- It requires high lubricant content.
3- Expensive sugar used as a tablet diluent.
4- It is widely used in chewable tablets because of its negative
heat of solution, its slow solubility and its mild cooling
sensation in mouth.
5- It can be used in vitamin formulation, where moisture
sensitivity may create a problem.
6- It non hygroscopic.
7- It is free from grittiness.
8- It possesses low caloric value and is non-cariogenic.

Lactose
Characteristics of -Lactose monohydrate (hydrous)
1-Use in wet granulation.
2- It has poor flow properties.
3- -lactose monohydrate is water soluble.
4- It produces a hard tablet and the tablet hardness increases
on storage.
5- Disintegrant is usually needed in lactose containing tablets.
6- Drug release rate is usually not affected.
7- It contains approximately 5% moisture and hence is a
potential source of instability especially with moisture
sensitive drugs.
8- It is inexpensive.

Characteristics of Lactose spray dried


1- It is directly compressible diluent.
2- It exhibits free flowing characteristics.
3- It needs high compression pressures in order to produce
hard tablets.
4- Usually, neutral or acid lubricant should be used when
spray dried lactose is employed.
5- Expensive compared to anhydrous and hydrous lactose.

Characteristics of Lactose anhydrous


1- Directly compressible diluent.
2- It does not exhibit free flowing property.
3- It can pick up moisture at elevated humidity as a result of
which changes in tablet dimensions may occur.
4- It is inexpensive.

Co-processed diluents
Co-processing means combining two or more materials by
an appropriate process.
The products so formed are physically modified in such
a special way that they do not loose their chemical structure
and stability
e.g. Sucrose 97% and modified dextrins 3% (Di-Pac)

Molded Tablets or Tablet Triturates


Tablet triturates are usually made from moist material
using triturate mold which gives them the shape of cut
sections of a cylinder. Such tablets must be completely and
rapidly soluble.

Buccal tablet
- Drug absorption is desired but fast drug absorption is not
intended.
- The tablets are designed not to disintegrate.
- They are flat elliptical or capsules shaped tablets as it can
be easily held between gum and cheek.
- Tablet kept for 30-60 minutes in oral cavity,
- Avoid gritty or irritating sensation.
- Used when replacement hormonal therapy is to be
administered. Antifungal drugs are preferred to be
administered by this route. e.g., Miconazole

B- Binders
Binders holds powders together to form granules
The quantity used and the method of application must be
carefully regulated, since the tablet must remain intact until
swallowed and must then release its medicament.
Why Granulation?
To improve powder flow.
To improve compressibility.
To reduce fines.
To control the tendency of powders to segregate.
To control density.
To capture and fuse small quantities of active material.

Binders powder mix the mixture wetted with water,


alcohol-water mixtures, or a solvent, or the binder may be put
into solution in the water or solvent and added to the powder.
Solution of the binder, requires much less binding
material to achieve the same hardness than if added dry.
In some cases, it is not possible to get granules of
sufficient hardness using the dry method. In practice, solutions
of binders are usually used in tablet production.

Types of Binders
CLASSIFICATION OF BINDERS
SUGARS

NATURAL BINDERS

SYNTHETIC/SEMISYNTHETIC
POLYMER

Sucrose

Acacia

Methyl Cellulose

Liquid glucose

Tragacanth

Ethyl Cellulose

Gelatin

Hydroxy Propyl Methyl Cellulose

Starch Paste

Hydroxy Propyl Cellulose

Pregelatinized Starch

Sodium Carboxy Methyl Cellulose

Alginic Acid

Polyvinyl Pyrrolidone (PVP)

Cellulose

Polyethylene Glycol (PEG)


Polyvinyl Alcohols
Polymethacrylates

CHARACTERISTICS OF COMMONLY USED BINDER


BINDER

Starch Paste

SPECIFIED
CONCENTRATION

5-10%w/w

Methyl 1-5%w/w
Cellulose

COMMENTS

- Freshly prepared starch paste is


used
- Its method of preparation is very
critical .
-A
5%
solution
produces
granulations similar in hardness
to 10% starch paste.
-Do not harden with age
-Better
binder
for
soluble
excipients such as lactose,
mannitol, and other sugars.
- Disintegrate more readily
- Used either in wet or dry
granulation processes.

Pregelatinized
Starch (PGS)

5-10%w/w
(Direct
Compression)
5-10 %w/w
(Wet
Granulation )

- Rupture all or part of the granules in


the presence of water and
subsequently dried.
- It contains 5% free amylose, 15%
free amylopectin and 80% unmodified
starch.
- Obtained from maize, potato or rice
starch.
- Used as a tablet binder, diluent,
disintegrant and flow aid.
- They enhance both flow and
compressibility and can be used as
binders in Direct Compression as well
as Wet Granulation.
- High purity PGS allow simplified
processing as they swell in cold water
and therefore reduce time/costs
compared with traditional starch paste
preparation.

Polyvinyl 0.5-5%w/w - Soluble in both water and alcohol.


Pyrrolidone
- Used in wet granulation process.
(PVP)
- It is also added to powder blends
in the dry form and granulated in
situ by the addition of water,
alcohol or hydroalcoholic solution.
- Valuable binder for chewable
tablets.
- The drug release is not altered on
storage.
Polyethylene
Glycol (PEG)
6000

1015%w/w

- Used as a meltable binder.


- Anhydrous granulating agent
where water or alcohol cannot be
used .
- It may prolong disintegration time
when concentration is 5% or higher
- It improves the plasticity of other
binders.

Direct compression (DC) Binders


Due to ease of manufacture, product stability and high
efficiency, the use of Direct Compression for tableting has
increased.
For Direct Compression, directly compressible binders
are required which should exhibit adequate powder
compressibility and flowability.

COMMONLY USED DC BINDERS


a- Microcrystalline Cellulose,
b- Microcrystalline Cellulose,
c- Pregelatinized Starch,
d- Dibasic Calcium Phosphate Dihydrate

Mechanism of granule formation


Granules are formed in three stages:
1- Nucleation:
2- Transition:
3- Ball growth or enlargement of the granule

C- Lubricants
Used to ease the ejection off the tablet from the
die to prevent sticking of tablets to the punches, and to
prevent excessive wear on punches and dies.
Solid lubricants, act by boundary mechanism, results
from the adherence of the polar portions of molecules with
long carbon chains to the metal surfaces to the die wall.
Magnesium stearate is an example of boundary lubricant.
Hydrodynamic mechanism i.e. fluid lubrication where
two moving surfaces are separated.
Lubricants should be incorporated in the final mixing
step, after granulation is complete.

Classification of lubricants
Lubricant are classified according to their water solubility
i.e. water insoluble and water soluble.

Water Insoluble Lubricants


Water insoluble lubricants are most effective and used at
reduced concentration than water soluble lubricants.
Since these lubricants function by coating, their
effectiveness is related with their surface area, extent of particle
size reduction, time, procedure of addition and length of mixing.

Water Soluble Lubricants


Water Soluble Lubricants are used when a tablet is
completely soluble or when unique disintegration and dissolution
characteristics are required.
Tablet containing soluble lubricant shows higher
dissolution rate than tablet with insoluble lubricants.

LIST OF INSOLUBLE LUBRICANTS


INSOLUBLE
LUBRICANTS

CONCENTR
ATION

COMMENTS

Stearates
(Magnesium
Stearate,
0.25 -1
Calcium
Stearate,
Sodium stearate)

-Reduce tablet strength


-Prolong
disintegration
and
dissolution due to hydrophobic
nature
-Widely used.

Talc

1 -2

-Insoluble but not hydrophobic


- Acts as both lubricant and glidant
-It
is
less
efficient
- It has the disadvantage of
retarding disintegration.

Waxes

15

- Not generally used as lubricants

Stearowet C

15

- less likely to interfere


disintegration and dissolution

Mineral oil

Up to 5

- Universal application because it is


unreactive, odorless, tasteless

with

Starch

Stearic acid

1- 2

-Derived from a number of


sources: corn, potato and rice
-Used as a filler, binder,
disintegrant and film-former
-It
is
available
both
as
hydrophilic and hydrophobic
corn starch.
- Most commonly used.
- More efficient lubricants

1-5

- less efficient lubricant


-Not melt under usual conditions
of storage
-It should not be used with
alkaline
salts
of
organic
compounds
-Causes sticking to the punches.

LIST OF SOLUBLE LUBRICANTS


WATER
SOLUBLE
LUBRICANTS

CONCENTRATION
(%W/W)

Boric acid

Sodium
benzoate

Sodium oleate

Sodium acetate

Sodium Lauryl
sulfate (SLS)

15

Magnesium
lauryl sulfate
(MLS)

1-2

COMMENTS

- Waterproofing properties
-It appears that magnesium
lauryl sulfate is at least as
efficient as magnesium
stearate and has the
advantage of reduced
interference with dissolution

In selecting a lubricant, the following should be


considered:
1- Lubricants reduce the bonding properties of many excipient.
2- Lubricants should be added last to the granulation and tumble
blended for not more than 10 min.
3- The optimum amount of lubricant must be determined for each
formulation. Excess lubricant is no more effective but rather
interferes with both disintegration and bioavailability by
waterproofing the granules and tablet.
4- Lubricant efficiency is a function of particle size; therefore, the
finest grade available should be used and screened through a
100 to 300-mesh screen before use.

D- Disintegrants
Disintegrant is the term applied to various agents
added to tablet granulation for the purpose of causing the
compressed tablet to break apart (disintegrate) when placed
in an aqueous environment.
The stronger the binder, the more effective must be
the disintegrating agent in order for the tablet to release its
medication.
Ideally, it should cause the tablet to disrupt, not only
into the granules from which it was compressed, but also
into the powder particles from which the granulation was
prepared.

Methods of addition of disintegrants


1- External addition
2- Internal addition
1- Mixing just prior to compression.
2- In the internal addition method, the disintegrant is mixed
with other powders before wetting the powder mixture with the
granulating solution. Thus, the disintegrant is incorporated
within the granule.
When this method is used, part of the disintegrant can be
added internally and part externally.
This provides immediate disruption of the tablet into the
previously compressed granules while the disintegrating agent
within the granules produces further erosion of the granules to
the original powder particles.

SCHEMATIC REPRESENTATION OF TABLET DISINTEGRATION AND


SUBSEQUENT DRUG DISSOLUTION

Types of disintegrants
Starch
Most widely used disintegrant
Starch 1500 is a physically modified cornstarch that meets all
the specifications of pregelatinized starch NF.
Starch thus functions as the classical disintegrant.
Starch 1500 versatile disintegrating agent as both an internal
and external disintegrant in tablet formulations.
Avicel (microcrystalline cellulose)
- Highly effective disintegrant.
-Fast wicking rate for water, hence, it and starch make an
excellent combination for effective and rapid disintegration
-Tendency to develop static charges with in creased moisture
content, sometimes causing striation or separation in the
granulation. To overcome drying the cellulose to remove the
moisture.
-It can be used with almost all drug except those that are
moisture-sensitive (such as aspirin, penicillin, and vitamins)

Solka floe (purified wood cellulose)


Used alone or in combination with starch as a disintegrating for
penicillin, and other drugs that are pH- and moisture-sensitive.
More effective when used in combination with clays such as kaolin,
bentonite, or Veegum.
This combination is especially effective in tablet formulations
possibly having a high moisture content (such as ammonium chloride,
sodium salicylate, and vitamins).

Alginic acid
Its affinity for water and high sorption capacity make it an excellent
disintegrant.
It is insoluble in water
Slightly acid in reaction,
Should be used only in acidic or neutral granulations.
It can be used with aspirin and other analgesic drugs.
If used with alkaline salts or salts of organic acids, it tends to form
soluble or insoluble alginates that have gelling properties and delay
disintegration.
It can be successfully used with ascorbic acid, multivitamin
formulations, and acid salts of organic bases.

Explotab (sodium starch glycolate)


Absorb water rapidly and swell.
Guar gum
Naturally occurring gum
It is a free-flowing, completely soluble, neutral polymer
composed of sugar units and is approved for food use.
It is available in various particle sizes and finds general
use as a tablet disintegrant.
It is not sensitive to pH, moisture content, or solubility of
the tablet matrix.
Excellent disintegrant
It is not always pure white, and it sometimes varies in
color from off-white to tan.
It also tends to discolor with time in alkaline tablet.

Polyclar AT (Polyplasdone XL and Polyplasdone XL 10)


Crosslinked, insoluble homopolymers
Ranges in particle size
Reduced mottling in tablet formulations.
Tablet hardness and abrasion resistance are less affected by
the addition of Polyplasdone XL as compared to starches,
cellulose, and pectin compounds.
Tendency toward tablet capping is reduced.
Polyplasdone XL provide rapid disintegration and improved
dissolution.
Amberlite IPR 88 (ion exchange resin)
Swell in the presence of water thereby acting as a disintegrant.
Care must be taken in the selection of a resin as a disintegrant
adsorb drugs upon them.
Anionic and cationic resins have been used to absorb
substances and release them when the charge changes.

Methyl cellulose, sodium carboxymethylcellulose, and


hydroxypropylcellulose
Swell on contact with water.
Used in conjunction with the above disintegrant

Mechanism of tablet disintegrants


The tablet breaks to primary particles by one or more of the
mechanisms listed below:1- By capillary action
2- By swelling
3- Because of heat of wetting
4- Due to disintegrating particle/particle repulsive forces
5- Due to deformation
6- Due to release of gases
7- By enzymatic action

Superdisintegrants
Passes faster disintegrating formulation is increased.
Superdisintegrants which are effective at low concentration
and have greater disintegrating efficiency and they are more
effective intragranularly.
Hygroscopic therefore not used with moisture sensitive
drugs.
Superdisintegrants act by swelling a

Mechanism of superdisintegrants by swelling

pt060479_figure1.wmv

LIST OF SUPERDISINTEGRANTS
SUPERDISINTE
GRANTS

EXAMPLE

MECHANISM OF
ACTION

Crosscarmellose

Crosslinked
cellulose

-Swells 4-8 folds in


< 10 seconds.
-Swelling and
wicking both.

-Swells in two dimensions.


-Direct compression or
granulation

Crosslinked
PVP

-Swells very little


and returns to
original size after
compression but act
by capillary action

-Water insoluble and


spongy in nature so get
porous tablet

Sodium starch
glycolate
Explotab
Primogel

Crosslinked
starch

-Swells 7-12 folds in


<30 seconds

-Swells in three dimensions


and high level serve as
sustain release matrix

Alginic acid NF
Satialgine

Crosslinked
alginic acid

-Rapid swelling in
aqueous medium or
wicking action

-Promote disintegration in
both dry or wet granulation

Ac-Di-Sol
Crosspovidone
Polyplasdone

SPECIAL COMMENT

Factors affecting disintegration


Effect of fillers
If soluble fillers are used then it may cause increase in viscosity of
the penetrating fluid which tends to reduce effectiveness of strongly
swelling disintegrating agents and as they are water soluble, they are
likely to dissolve rather than disintegrate.
Insoluble diluents produce rapid disintegration with adequate
amount of disintegrants.
Effect of binder
As binding capacity of the binder increases, disintegrating time of
tablet increases
Effect of lubricants
Mostly lubricants are hydrophobic this hydrophobic coating
inhibits the wetting and consequently tablet disintegration.
Effect of surfactants
Surfactants are recommended to decrease the hydrophobicity of
the drugs because the more hydrophobic the tablet the greater the
disintegration time. The speed of water penetration was increased by
the addition of a surfactant.

Glidants
Glidants are materials that improve the flow
characteristics of granulations by reducing interparticulate
friction.
The effects produced by different glidants depend on
(a)Chemical nature of the powder or granule (i.e., the
presence of unsaturated valences, ionic or hydrogen bonds on
the respective surfaces that could interact chemically)
(b) Physical factors including particle size, shape, and
distribution of the glidant and various other formulation
components, moisture content, and temperature.
Hydrophilic glidants tend to be more effective on
hydrophilic powders, and the opposite is true for hydrophobic
glidants.

The improvement is dependent on the size and concentration


of the fine particles; the smaller the particles, the lower the
concentration required to produce an increased flow.
Silica-type glidants
- Most efficient probably because of their small particle size
- Improved the flow properties of granulations as reflected
- In increased tablet weight
- In decreased weight variation in the tablets.
They are available as two types, both insoluble:
(a)the pyrogenie silicas prepared by burning silicon
tetrachloride in an atmosphere of oxygen
(b) the hydrogels, which are prepared by the precipitation of
soluble silicates.

Coloring Agents
Colors in compressed tablets serve functions other than
making the dosage form more esthetic in appearance.
Serving as a means of identification to the user.
A color lake is the combination by adsorption of watersoluble dye to a hydrous oxide of a heavy metal resulting in an
insoluble form of the dye.
The most common method of adding color to a tablet
formulation is to dissolve the dye in the binding solution prior to
the granulating process.
Anther approach is to adsorb the dye on the starch or
calcium sulfate from its aqueous solution, the resulting powder
is dried and blended with the other ingredients.

Frequently during drying, colors in wet granulations


migrate, resulting in an uneven distribution of the color in the
granulation.
After compression the tablets will have a mottled
appearance due to the uneven distribution of the color.
Migration of colors may be reduced by drying the
granulation slowly at low temperatures and stirring the
granulation while it is drying.
Water-soluble anionic dyes for natural starches has
been demonstrated to preventing color migration.
Other additives have been shown to act as dye
migration inhibitors. Tragacanth (1%) acacia (3%, and talc 7%)

Prevention of mottling can be helped also by the use of


lubricants and other additives which have been colored
similarly to the granulation prior to their use.
Color mottling is an undesirable characteristic common
to many commercial tablets.

Flavours
Flavors are commonly used to improve the taste of
chewable tablets as well as mouth dissolved tablets.
Flavors are incorporated either as solids (spray dried
flavors) or oils or aqueous (water soluble) flavors.
Solids that is dry flavors are easier to handle and
generally more stable than oils.
Oil is usually added at the lubrication step because of its
sensitivity to moisture and their tendency to volatilize when
heated during drying.
The maximum amount of oil that can be added to
granulation without affecting tableting characteristics is 0.5 to
0.75 %w/w.
Aqueous flavors are less used because of its instability
on aging.

Sweeteners
Sweeteners are added primarily to chewable tablets.
Saccharin is 500 times sweeter than sucrose.
Disadvantages has a bitter after taste and is carcinogenic.
Aspartame is about 180 times sweeter than sucrose.
Disadvantage its lack of stability in the presence of moisture.

SOME OF THE SWEETENERS USED IN TABLET FORMULATION


NATURAL SWEETENERS

ARTIFICIAL SWEETENERS

Mannitol
Lactose
Sucrose
Dextrose

Saccharin
Cyclamate
Aspartame

Adsorbents
Adsorbents are substances capable of holding quantities
of fluids in an apparently dry state.
Silicon dioxide, for example, possesses a vast surface
area, it can hold up to 50% of its weight in water and still act as
a free-flowing powder. It readily absorbs and releases water,
thus being very useful with hygroscopic materials.
Magnesium carbonate and magnesium oxide are
employed with drug extracts which contain oily components,
unless the extracts are sensitive to alkali.
Other substances that may serve as adsorbents are
bentonite, kaolin, magensium aluminum silicate, and tricalcium
phospphate.
Combinations of these various excipients are also
feasible
Dried starch can be used as disintegrant and also as
adsorbent.

Preparation of Components for Compression:


Methods preparing tablets. These are:
1. Dry methods.
a. Direct compression.
b. Granulation by compression.
2. Wet methods.
a. Wet granulation.
b. Special procedures.
The dry methods are superior to those employing liquids,
since these dry processes do not require the equipment and
handling expenses required in wetting and drying procedures.

The direct
manufacture

compression

process

tablet

Diluent

Active ingredient(s)

Lubricant

of

Mixing

Disintegrant agent

Compression

Glidant

Directly Compressible Vehicles:


A directly compressible vehicle is an inert substance
Compressible diluents currently available are spray dried
lactose, anhydrous lactose, calcium phosphate, mannitol,
sorbitol, and microcrystalline cellulose as single entities.
Most of the characteristics of a good, directly
compressible vehicle have already been described before.
Others are: rapid disintegration, physiological inertness,
tastelessness, ability to be reworked, capacity for poorly
compressible ingredients, and cheapness.

Limitations to the use of these materials:


1. Difference is particle size and bulk density between the
diluent and the active ingredient may lead to stratification and
variation in drug content of tablets.
2. Unless the drug itself is easily compressible, the amount
present is limited to a maximum of 30% of the tablet weight.
3. The drug may interact with the vehicle as amine
compounds do with spray dried lactose.
4. Static charges that have developed on the drug during
comminution and mixing may prevent uniform distribution.

The directly compressible vehicles now in use


1. Anhydrous lactose
Directly compressible
Good flow properties.
Reduced to a finer state of subdivision without loss of
compressibility.
2. Spray dried lactose
Roughly spherical or consists of spherical aggregates and thus
has improved flow.
Combination, of microcrystal's and amorphous solids produces
a form that has good compressibility.
Unfavorable characteristics
(a)loss of flow and compressibility when reworked or milled,
(b) a browning reaction which occurs in the presence of basic
compounds such as amines, this reaction. Moisture has also
been shown to be a contributing factor
(c) a loss of compressibility if the usual content of
approximately 3% water is lost on storage.

3. Dicalcium phosphate dihydrate


- Moderately coarse
- Can be compressed directly.
- Its flow properties are adequate
- Capable of being compressed into tablets directly when
blended with active ingredients.
4. Emcompress
- Is an agglomerated form of dicalcium phosphate with a
distinctive particle size and excellent compressibility.
- Cohesiveness increases its capacity for other substances
in the formulation.
- Great fluidity makes it ideal for compression on high
speed machines.
- It is stable in normal storage and does not absorb
moisture.
- Its pH is slightly above neutral.

In several instances, tablets containing a new drug


and dicalcium phosphate dihydrate and stored for as long
as 12 weeks at 40 and 50C lost 10% or more of their
original weight.
This is equivalent to one mol of water.
Such a loss did not occur at room temperature nor at
high humidity conditions such as 35C/85%.
No degradation of the active ingredient took place
nor did the phenomenon happen with all the drugs which
were formulated with this base material.

5. Granular mannitol
-Developed especially as a directly compressible vehicle for
chewable tablets.
-It flows easily and improved fluidity to high levels of materials
which normally do not flow.
-Cannot be used with concentrations of other materials
exceeding 25% by weight.
6. Crystalline sorbitol
-Use a vehicle for chewable multivitamin tablets.
-It is hygroscopic. Because of its hygroscopicity, it is
susceptible to lumping in storage and cannot generally be
milled
-Reduction in particle size will result in poor flow.
7. Microcrystalline cellulose
Extremely compressible material.
The majority of these microcrystals range in size from 1 to 10
microns.

Tableting is a Compaction Process and Involves


Two Steps

View of Punch Train

Double-Ended Compression Rotary (Multistation)


Press

Dry granulating, Slugging, or Roller compaction


Mixed powders into an object to be reground into a precise
powder.
This action increases particle density, improves powder flow
and captures fines.
1. Granulate materials which are sensitive to heat and/or
moisture.
2. Produce a uniform particle size range.
3. Improve flow properties.
4. Control dust.
5. Control bulk density.
6. Produce uniform blends
7. Control particle hardness.
8. Improve wetting or dispersion rates

The dry granulation process of tablet manufacture


Active ingredient(s)

Diluent
Mixing

Binder

Lubricant
First compression
(by tablet press or roller compactor)

Milling
Sieving
Lubricant
Disintegrant agent

Mixing
Second compression

Glidant

-Powders can be compacted using a tablet press; this is called


Slugging.
-Once slugging is completed or powders are compacted on a
Roller Compactor, they are milled.
-Only sufficient pressure to compact the mass is used
-The speed of the press should be regulated so that firm slugs
may be produced.
-During subsequent milling they will break
down into granules without developing
excessive amounts of fine powder.
-Slugging utilizes less equipment
and space than wet granulating.

The wet granulation process of tablet manufacture


Active ingredient(s)
Water

Mixing

Diluent

Wetting

Binder
Granulation
Drying

Sieving
Lubricant
Disintegrant agent

Mixing
compression

Glidant

The mass should moist rather than wet or pasty,


The solution should be fluid enough to disperse readily in the
mass
This kneading of the mass in large blenders requires 15
minutes to an hour.
The length of time depends on the wetting properties of the
powder mixture and the granulating fluid, and upon the efficiency
of the mixer.
The moist mass is broken up into coarse, granular aggregates
by passing it through a hammer mill or oscillating granulator
equipped with screens with large perforations.
The purpose is to increase surface area to facilitate removal of
moisture.
After drying, the granulation is screened again, the size of the
screen depending upon the grinding.

Special Procedures
There are several other ways to prepare granulations,
all of which combine wetting the powders to form granules and
drying them in the same piece of equipment.
One method is with the spray dryer.
The drug may now be mixed with this base in
proportions as high as one to one.
If the drug is stable to the temperatures and solvents
used, it may be included in the slurry.

Cdi.exe

Proposed Manufacturing Process

Problems in tablet manufacturing


An ideal tablet should be free from any visual defect or
functional defect.
I. Tableting Process
II. Excipient
III. Machine
A- BINDING
B- STICKING, PICKING and FILMING
C- CAPPING and LAMINATION
D- CHIPPING and CRACKING
E- MOTTLING
F- WEIGHT VARIATION
G- HARDNESS VARIATION
H- DOUBLE IMPRESSION

A.Binding
Definition : Binding in the die or difficult ejection is usually
due to insufficient lubrication.
Reason: Binding is usually due to excessive amount of
moisture in granules, lack of lubrication and/or use of worn
dies.
This may be overcome by
1. Increasing lubrication.
2. Using a more efficient lubricant.
3. Improving the distribution of the lubricant by screening
through an 30-mesh screen
4. Reducing the size of the granules.
5. Increasing the moisture content of the granulation.
6. Reduce pressure .
7. Compressing at a lower temperature and/or humidity

B. Sticking, Picking, and Filming:


Definition: Sticking refers to the tablet material adhering to
the die wall.
Picking is a form of sticking in which a small portion of
granulation sticks to the punch face and grows with each
revolution of press, picking out a cavity on the tablet face.
Filming is a slow form of picking and is largely due to excess
moisture in the granulation, high humidity, high temperature,
or loss of highly polished punch faces due to wear.
Reason: Improperly dried or improperly lubricated granules.
Picking is of particular concern when punch tips have
engraving or embossing letters

These may be overcome by:


1. Decreasing the moisture content of the granulation.
2. Changing or decreasing the lubricant.
3. Adding an adsorbent (i.e., silica aerogel, aluminum
hydroxide, microcrystalline cellulose).
4. Polishing the punch faces.
5. Cleaning and coating the punch faces with light
mineral oil, low-viscosity dimethylpolysiloxane.

C- Capping and Lamination


Definition: Capping is the term used, when the upper or lower
segment of the tablet separates horizontally, either partially or
completely from the main body of a tablet and comes off as a
cap, during ejection from the tablet press, or during
subsequent handling.
Reason: Capping is usually due to the airentrapment in a
compact during compression, and subsequent expansion of
tablet on ejection of a tablet from a die.

Lamination
Definition: Lamination is the separation of a tablet into two
or more distinct horizontal layers.

Reason: Airentrapment
during
subsequent release on ejection.
exaggerated by higher speed of turret.

compression
and
The condition is

Possible cause of
capping/lamination

To overcome capping and laminating:


1. Changing the granulation procedure.
2. Increasing the binder.
3. Adding dry binder such as pregelatinized starch, gum
acacia, powdered sorbitol, PVP, hydrophilic silica, or
powdered sugar.
4. Increasing or changing lubrication.
5. Decreasing or changing lubrication.
6. Decreasing the upper punch diameter by 0.0005 in. to
0.002 in. depending on the size.

D- Chipping and Cracking


Definition: Chipping is defined as the breaking of tablet
edges, while the tablet leaves the press or during
subsequent handling and coating operations.
Reason: Incorrect machine settings, specially mis-set
ejection take-off.

Cracking
Definition: Small, fine cracks observed on the upper and
lower central surface of tablets, or very rarely on the sidewall
are referred to as Cracks.
Reason: It is observed as a result of rapid expansion of tablets,
especially when deep concave punches are used.

These problems may be overcome by one or more of the


following:
1. Polishing punch faces.
2. Reducing fines.
3. Reducing granule size.
4. Replacing nicked or chipped punches.
5. Adding dry binder such as pregelatinized starch, gum acacia,
PVP, spray-dried corn syrup, powdered sugar, or finely
powdered gelatin.

E- Mottling
Definition: Mottling is the term used to describe an unequal
distribution of colour on a tablet, with light or dark spots
standing out 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.

These problems may be overcome by one or more of the


following:
1- Use appropriate colourants
2- Change the solvent system
3- Change the binder
4- Reduce drying temperature
5- Use a smaller particle size
6- Mix properly and reduce size if it is of a larger size to
prevent segregation.
7- Incorporate dry colour additive during powder blending
step, then add fine powdered adhesives such as acacia and
tragacanth and mix well and finally add granulating liquid.

F. Weight Variation:
When a granulation is unsatisfactory, each tablet made from it
may vary in weight beyond accepted norms.
The causes are four:
1. The size and distribution of the granules being compressed.
2. Poor flow. When the granulation does not flow readily, it
tends to move spasmodically through the feed frame so that
some dies are incompletely filled.
3. Poor mixing. Sometimes the lubricants and glidants have
not been thoroughly distributed. The flow of particles is
impaired and the granules do not move efficiently into the dies.
4. Punches, When lower punches are of unequal lengths-the
difference may be only a few thousandths of an inch-the fill
each die varies because the fill is volumetric.

G. Hardness variation:
Hardness depends on the weight of material and the
space between the upper and lower punches at the moment
of compression. If the volume of material varies or the
distance between punches varies, hardness likewise is
inconsistent.
The degree of hardness of the tablet depends on its
physical size and shape together with the characteristics of
the chemicals that go into the formulation and the pressure
applied during compression.
If the tablet initially is too hard, it may not disintegrate in
the requisite period of time. Should it be too soft, it may not
withstand the necessary multiple shocks occurring during
handling, shipping, and dispensing.

H- Double impression
Definition: Double Impression involves only those
punches, which have a monogram or other engraving on
them.
Reason: At the moment of compression, the tablet receives
the imprint of the punch. Now, on some machines, the lower
punch freely drops and travels uncontrolled for a short
distance before riding up the ejection cam to push the tablet
out of the die, now during this free travel, the punch rotates
and at this point, the punch may make a new impression on
the bottom of the tablet, resulting in Double Impression.
If the upper punch is uncontrolled, it can rotate during the
short travel to the final compression stage and create a
double impression.

TABLET CHARACTERISTICS
Compressed tablets may be
described by a number of specifications.

characterized

or

Content uniformity
Diameter size
Shape
Thickness
Weight
Hardness
Disintegration time
Dissolution time
The diameter and shape depend on the die and the
punches selected for the compression of the tablet.

QUALITY CONTROL FOR TABLETS


1.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.
The force is measured in kilograms and when used in
production, hardness of 4 kg is considered to be minimum for a
satisfactory tablet.
If the tablet is too hard, it may not disintegrate in the
required period of time, if it is too soft it will not withstand the
handling during packaging and shipping operations.

2- Friability test
Evaluate the ability of the tablet to withstand abrasion in
packaging, handling, and shipping.

3- Tablet Thickness
The thickness of the tablet from production run to
production-rum is carefully controlled.
Thickness can vary with no change in weight due to
difference in the density of the granulation and the pressure
applied to the tablets, as well as the speed of tablet
compression.
Not only is the tablet thickness important in reproducing
tablets identical in appearance but also to insure that every
production lot will be usable with selected packaging
components.
Tablet thickness is determined with a caliper or thickness
gauge which measures the thickness in millimeters.

4- Tablet Weight
The volumetric fill of the die cavity determines the
weight of the compressed tablet.
After the tablet machine is in operation the weights of
the tablets are checked routinely to insure that proper weight
tablets are being made.
Twenty tablets are weighed individually and the average
weight is calculated.
Large Weight

Percentage Difference

130 mg or less

10

More than 130 mg through 324 mg

7.5

More than 324 mg

5- Content Uniformity
In order to ensure that every tablet contains the amount
of drug substance intended with little variation among tablets
within a batch.
The required specification for this test is that uniformity
of dosage unit should be within a range of 85%115% with a
relative standard deviation of less than or equal to 6%.

6- Tablet Disintegration
To be absorbed, a drug substance must be in solution and
the disintegration test is a measure only of the time required
under a given set of conditions for a group of tablets to
disintegrate into particles.
The disintegration test is used as a control for tablets
intended to be administered by mouth, except where tablets
are intended to be chewed before being swallowed or where
tablets are designed to release the drug substance over a
period of time.
Fluid is usually water at 37C, but in some cases the
monographs direct that Simulated Gastric Fluid used.
For most uncoated tablets the period is 30 min.
For coated tablets up to 2 hours may be required
For sublingual tablets time is 3 min.

7- Dissolution Test
Measuring the amount of time required for a given
percentage of the drug substance in tablet to go into solution
under a specified set of conditions in an in vitro test.
It is intended to provide a step towards the evaluation of
the physiological availability of the drug substance,
Both the safety and effectiveness of a specific dosage
form must be demonstrated initially by means of appropriate in
vivo studies and clinical evaluation.
Provides an in vitro control procedure to eliminate
variations among production batches.

Many procedures have been proposed for determining the


dissolution rates of active substances from solid dosage
forms.
Three types of apparatus are officially recognized
Apparatus I (USP basket method)
Apparatus 2 (USP paddle method)
Apparatus 3 (modified disintegration equipment method).
The basket method is preferred by the USP unless otherwise
indicated in the monograph.

Tablet Coating
The purpose of tablet coating is to
1. Enhance palatability and mask the unpleasant taste and odor
of the active drug substance
2. Increase the stability of an active drug substance during
exposure to light, moisture and atmospheric oxygen
3. Increase the mechanical integrity of the tablet during
manufacturing, packaging and shipping
4. Enhance the elegance and glossy appearance of the tablet
core
5. Protect the patients clothes and hands from staining due to a
colored or migrating active drug substance

6. Modify the drug release profile, such as with an enteric


coating, sustained release coating, osmotic pump, etc.
7. Avoid side effects caused by the active drug substance (i.e.
prevention of gastric irritation by employing an enteric polymer
coating)
8. Avoid incompatibility of active drug substances by physical
separation of the incompatibles into the core and coat
9. Identify the product using a coating unique to a particular
manufacturer

Sugar coating Tablets


The sugar coating of tablets may be divided into the
following steps:
1) waterproofing and sealing (if needed)
2) subcoating
3) smoothing and final rounding
4) fishing and coloring (if desired)
5) polishing

Waterproofing and Sealing Coats.


For tablets affected by moisture
The waterproofing solution (usually alcoholic)
Warm air is blown into the pan during the coating to enhance
the drying and to prevent tablets from sticking together.
Ex. shellac, cellulose acetate phthalate, polyvinyl acetate
phthalate.
Subcoating
3 to 5 subcoats of a sugar-based syrup are applied.
The sucrose and water syrup also contains gelatin, acacia, or
(PVP) to enhance the coating of the tablets.
When the tablets are partially dry they are spray with a
dusting powder, usually a mixture of powdered sugar and starch
but sometimes talc, acacia
Warm air is applied to the rolling tablets
Subcoating process is repeated until the tablets are of the
desired shape and size.

Smoothing and Final Rounding


addition of simple syrup
This syrup is sucrose-based with or without additional
components as starch and calcium carbonate.
Warm air is applied to hasten the drying time of each coat.

Finishing And Coloring


More simple syrup, containing dyes (water-soluble) or
pigments (water-insoluble).
Use of water-soluble dyes necessitates smooth application
and slow drying to avoid migration, which would ruin the
desired uniform appearance

Imprinting
Uses pharmaceutical grade printing inks to provide
additional identification

Polishing
The main purpose of polishing is to obtain a
transparent, glossy and reflective coating with no opalescence
or cloudiness remaining from previous steps.
Makes the product more stable upon storage
The polishing step can be performed by incorporating
waxes, fats
Two or three coats of wax may be applied depending
upon the desired gloss.

Disadvantage of sugarcoating
1- Tedious
2- Time-consuming
3- Specialized, requiring the expertise of highly skilled
technicians
4- Increase weight of the original uncoated tablets.
5- Vary slightly in size from batch to batch and within a batch.
6- Large tablets are not as easily swallowed as are small
tablets

Film-Coating Tablets
A film coating is defined as a thin and uniform polymer
based coat of about 20 to 100 m in thickness, which is applied
to the surface of substrates such as tablets, granules, powder,
capsules, or pellets.

Advantages of Film Coating


1. Enhance the elegance and glossy appearance of the dosage
form
2. Product identification after coating
3. Improve mechanical integrity and resistance of the dosage
form upon handling and shipping from manufacturing site to
patients
4. Modify the pharmaceutical function of the dosage form,
especially for enteric or modified release coating

5. Increase flexibility in types of formulations coated and


processing equipment required
6. Minimal weight increase (about 2-3 % of tablet core weight)
compared to a sizeable increase when using a sugar coating
(doubling the weight of tablet core)
7. Significantly reduced processing time, with increased
process efficiency and output
8. Minimize dusting

Film-coating solutions may be nonaqueous or aqueous.


The nonaqueous solutions contain the following types of
materials to provide the desired coating to the tablets:
1. A film former capable of producing smooth, thin films
reproducible under conventional coating conditions and
applicable to a variety of tablet shapes. Example: cellulose
acetate phthalate.
2. An alloying substance providing water solubility or
permeability to the film to ensure penetration by body fluids
and therapeutic availability of the drug. Example:
polyethylene glycol.
3. A plasticizer to produce flexibility and elasticity of the coating
and thus provide durability. Example: castor oil,

4. A surfactant to enhance spreadability of the film during


application. Example: polyoxyethylene sorbitan derivatives.
5. Opaquants and colorants to make the appearance of the
coated tablets handsome and distinctive. Examples: Opaquant,
titanium dioxide; colorant, FD & C or D & C dyes.
6. Sweeteners, flavors, and aromas to enhance the
acceptability of the tablet to the patient. Examples: sweeteners,
saccharin; flavors and aromas, canillin.
7. A glossant to provide luster to the tablets without a separate
polishing operation. Example: beeswax.
8. A volatile solvent to allow the spread of the other
components over the tablets while allowing rapid evaporation to
permit an effective yet speedy operation. Example: alcoholacetone mixture.

Disadvantages of Organic Solvent Systems


1. Environmental, fire and toxicity hazards
2. Requires flameproof equipment to reduce hazardous
working environment for the operator.
3. Residual solvent from coating process.
4. Requires solvent recovery systems.
5. High cost of the process due to the required use of special
safety equipment with organic solvents.

AQUACOAT water-based colloidal coating dispersion


and contains a 30% ethyl cellulose pseudolatex.
Pseudolatex dispersions have high solids content for
greater coating ability and a relatively low viscosity.
The low viscosity allows less water to be used in the
coating dispersion, resulting in a lesser requirement for waterevaporation and a reduced likelihood of water interference with
the tablet formulation.
A plasticizer may be incorporated into the dispersion to
assist in the production of a denser, less-permeable film, with
higher gloss and greater mechanical strength.

A typical aqueous film-coating formulation contains the


following:
1. Film-forming polymer (7-18%). Examples: cellulose ether
polymers as hydroxypropyi methylcellulose, hydroxypropyi
cellulose, and methylcellulose.
2. Plasticizer (0.5-2.0%). Examples: glycerin, propylene glycol,
diethyl phthalate, and dibutyl subacetate.
3. Colonant and opacifier (2.5-8%). Examples: FD & C or D & C
Lakes and iron oxide pigments.
4. Vehicle (water, to make 100%).

Erosion of the tablet edge due to a soft or friable tablet or


because the pan was turning too fast or both.
Peeling and breakage also appear here.

These tablets likely broke because they had poor hardness.

Very porous tablet that prevented the coating from adhering to


the surface.
These tablets should have been coated longer, and the
atomization pressure should have been reduced to decrease
the slight orange peel, or textured, surface.

I attribute the peeling to excessive moisture within the tablet,


which prevented the coating from adhering.
a picking defect. That is usually caused by over-wetting the
tablet or by a tablet that is too soft.

Picking and sticking.


This is when the coating removes a piece of the tablet
from the core. It is caused by over-wetting the tablets, by underdrying, or by poor tablet quality.

Bridging.
This occurs when the coating fills in the lettering or logo
on the tablet and is typically caused by improper application of
the solution, poor design of the tablet embossing, high coating
viscosity, high percentage of solids in the solution, or improper
atomization pressure.
Erosion.
This can be the result of soft tablets, an over-wetted
tablet surface, inadequate drying, or lack of tablet surface
strength.

Twinning
This is the term for two tablets that stick together, and its
a common problem with capsule shaped tablets. Assuming you
dont wish to change the tablet shape,
You can solve this problem by balancing the pan speed
and spray rate.

Peeling and frosting


This is a defect where the coating peels away from the
tablet surface in a sheet.
This could be due to a defect in the coating solution, overwetting, or high moisture content in the tablet core.

Mottled color
This can happen when the coating solution is improperly
prepared, the actual spray rate differs from the target rate, the
tablet cores are cold, or the drying rate is out of spec.

Enteric Coating
Enteric coated solid dosage forms are intended to pass
through the stomach intact to disintegrate and release their drugcontent for absorption along the intestines.
Enteric coating materials may be applied to either whole
compressed tablets or to drug particles or granules used in the
subsequent fabrication of tablets or capsules.
The coating may be applied in multiple portions to build a
thick coating or they may be applied as a thin film coat.
The coating systems may be aqueous-based or organicsolvent-based and are effective so long as the coating material
resists breakdown in the gastric fluid
Materials used in enteric coatings are pharmaceutical
shellac,
hydroxypropyi methylcellulose phthalate, polyvinyl
acetate phthalate, diethyl phthalate, and cellulose .acetate
phthalate.