UNIT-2 TABLETS & COATING OF TABLETS

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Nov 29, 2013 (3 years and 8 months ago)

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Pharmaceutics
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VII (Pharmaceutical Technology
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PHARM
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362


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UNIT
-
2 TABLETS & COATING OF TABLETS


Pharmaceutical formulation
,
in
pharmaceutics
, is the process in which different chemical substances, including the
active
drug
, are combined to produce a final
medicina
l product
.

The way a drug is formulated can avoid some of the problems associated with
oral administration
.

Drugs are normally taken orally as tablets or caps
ules.

The drug (
active substance
) itself needs to be
soluble

in
aqueous

solution at a controlled rate. Such factors as
particle size

and
crystal

form can significantly affect
dissolution
. Fast dissolution is not always ideal. For example, slow dissolution rates can
prolong the duration of action or avoid initia
l high
plasma

levels. Treatment of active ingredient by special way as spherical
crystallization

can have some advantages for drug formulation.

Tablet form

A tablet is usually a
compressed preparation that contains:

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

80% of
fillers
,
disintegrants
,
lubricants
,
glidants
, and
binders
; and

10% of compounds which ensure easy
disintegration
,
disaggregation
, and dissolution of the tablet in the
stomach

or the
intestine
.

The disintegration 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
.

Some tablets are designed with an
osmotically

active core, surrounded by an impermeable membrane with a pore in it. This
allows the drug to
percolate

out from the tablet at a constant rate as the tablet moves through the
digestive tract
.

Tablets Dosage form
is one of a most prefered dosage form all over the world


Almost all drug molecules can be formulated in a tablet and process of manufactiring of tablets too is very simple , and is v
ery
flexible.


One can administere 0.01 mg of a drug dose to 1 gm of a
drug dose by oral route of administration , by formulating as a
tablet.


Tablet Dosage Forms

The tablet is the most commonly used oral dosage form. It is also quite complex in nature. The biggest problem is overcoming
the reduction in effective surface ar
ea produced during the compression process. One may start with the drug in a very fine
powder, but then proceeds to compress it into a single dosage unit.

Ingredients

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Tablet ingredients include materials to break up the tablet formulation.

Drug
-

may be poorly soluble, hydrophobic

Lubricant
-

usually quite hydrophobic

Granulating agent
-

tends to stick the ingredients together

Filler
-

may interact with the drug, etc., should be water soluble

Wetting agent
-

helps the penetration of wate
r into the tablet

Disintegration agent
-

helps to break the tablet apart

Coated tablets are used to mask an unpleasant taste, to protect the tablet ingredients during storage, or to improve the
tablets appearance. Another barrier is placed between the so
lid drug and drug in solution. This barrier must break down
quickly or it may hinder a drug's bioavailability.

Tablet


Common disk
-
shaped tablets

A
tablet

is a
pharmaceutical

dosage form. It comprises a mixture of active substances and
excipients
, usually in
powder

form,
pressed or compacted from a powder into a solid dose. The excipients can include diluents, binders or granulating agents,
glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to promote tablet break
-
up in the digestive
tract; s
weeteners or flavours to enhance taste; and pigments to make the tablets visually attractive. A polymer coating is
often applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to mak
e
it more resist
ant to the environment (extending its shelf life), or to enhance the tablet's appearance.

The compressed tablet is the most popular
dosage form

in use today. About two
-
thirds of all
prescriptions

are dispensed as
solid dosage forms, and half of these are compressed tablets. A tablet can be formulated to deliver an accurate dosage to a
specific
site; it is usually taken orally, but can be administered
sublingually
, buccally,
rectally

or
intravaginally
. The tablet is
just one of the many forms that an oral drug can take such as
syrups
,
elixirs
,
suspensions
, and
emulsions
. Medicinal tablets
were originally made in the shape of a disk of whatever color their components determined, but are now made in many
shapes and colors to help distinguish different medicines. Tablets are often stamped with symbols, letters, and numbers,

which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter.
Some tablets are in the shape of
capsules
, and

are called "caplets". Medicinal tablets and capsules are often called pills. This
is technically incorrect, since tablets are made by compression, whereas pills are ancient solid dose forms prepared by rolli
ng
a soft mass into a round shape. Other product
s are manufactured in the form of tablets which are designed to dissolve or
disintegrate; e.g. cleaning and deodorizing products.

Tabletting formulations

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In the tablet
-
pressing process, it is important that all ingredients be fairly dry, powdered or granul
ar, somewhat uniform in
particle size, and freely flowing. Mixed particle sized powders can segregate during manufacturing operations due to differen
t
densities, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content u
niformity but
granulation

should prevent this. Content uniformity ensures that the same API dose is delivered with each tablet.

Some APIs ma
y be tableted as pure substances, but this is rarely the case; most formulations include
excipients
. Normally, an
pharmacologically inactive ingredient (excipient) termed a
binder

is add
ed to help hold the tablet together and give it
strength. A wide variety of binders may be used, some common ones including
lactose
, dibasic calcium phosphate,
sucrose
,
corn (maize) starch, microcrystalline
cellulose
, povidone
polyvinylpyrrolidone

and modified cellulose (for example
hydroxypropyl methylcellulose and hydroxyethylcellulose).

Often, an ingredient is also needed to act as a
disintegrant

to aid tablet dispersion once swallowed, releasing the API for
absorpti
on. Some binders, such as starch and cellulose, are also excellent disintegrants.

Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate and calcium
stearate.

Advantages and disadvantages

Variations on a comm
on tablet design, which can be distinguished by both color and shape

Tablets are simple and convenient to use. They provide an accurately measured dosage of the active ingredient in a
convenient portable package, and can be designed to protect unstable med
ications or disguise unpalatable ingredients.
Colored coatings, embossed markings and printing can be used to aid tablet recognition. Manufacturing processes and
techniques can provide tablets special properties, for example, sustained release or fast diss
olving formulations.

Some drugs may be unsuitable for administration by the oral route. For example, protein drugs such as insulin may be
denatured by stomach acids. Such drugs cannot be made into tablets. Some drugs may be deactivated by the
liver

when they
are carried there from the gastrointestinal tract by the
hepatic portal vein

(the "first pass effect"
), making them unsuitable for
oral use. Drugs which can be taken sublingually are absorbed through the oral
mucosae
, so that they bypass the liver and are
less susceptible to the first pass effect. The oral bioavailability of some drugs may be low due to poor absorption from the
gastrointestinal tract. Such drugs may need to be given in very high doses or by injection.

For drugs that need to have rapid
onset, or that have severe side effects, the oral route may not be suitable. For example
salbutamol
, used to treat problems in
the pulmonary system,
can have effects on the heart and circulation if taken orally; these effects are greatly reduced by
inhaling smaller doses direct to the required site of action.

Tablet properties

Tablets can be made in virtually any shape, although requirements of patient
s and tableting machines mean that most are
round, oval or capsule shaped. More unusual shapes have been manufactured but patients find these harder to swallow, and
they are more vulnerable to chipping or manufacturing problems.

Tablet diameter and shape a
re determined by the machine tooling used to produce them
-

a die plus an upper and a lower
punch are required. This is called a station of tooling. The thickness is determined by the amount of tablet material and the

position of the punches in relation to

each other during compression. Once this is done, we can measure the corresponding
pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure
applied during compression, and sometimes the harder
the tablet. Tablets need to be hard enough that they don't break up
in the bottle, yet friable enough that they disintegrate in the gastric tract.

Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist

and patient.
The mechanical strength of tablets is assessed using a combination of (i) simple failure and erosion tests, and (ii) more
sophisticated engineering tests. The simpler tests are often used for quality control purposes, whereas the more complex

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tests are used during the design of the formulation and manufacturing process in the research and development phase.
Standards for tablet properties are published in the various international pharmacopeias (USP/NF, EP, JP, etc.). The hardness

of tablets i
s the principle measure of mechanical strength. Hardness is tested using a hardness tester. The units for hardness
have evolved since the 1930s.

Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule fillin
g machine.
Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.

Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most
frequently used lubricants in tablets or hard gelatin capsules.

Manufacturing

Manufacture of the tableting blend

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.

W
et granulation

Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to
be properly controlled, as over
-
wetting will cause the granules to be too hard and under
-
wetting will cause them to
be too
soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvent
-
based systems but may not be
suitable for drugs which are degraded by hydrolysis.

Procedure

The active ingredient and excipients are weighed and mixed.

T
he 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 cornstarch, natural gums such as acacia, cellulose derivatives such as
methyl cellulo
se,
gelatin
, and povidone.

Screening the damp mass through a mesh to form pellets or granules.

Drying the granulation. A conventional tray
-
dryer or fluid
-
bed dryer are most commonly used.

Af
ter the granules are dried, they are passed through a screen of smaller size than the one used for the wet mass to create
granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can take a considerable time to ac
hieve a
uniformly mixed state. High shear wet granulation processes use equipment that mixes the powder and liquid at a very fast
rate, and thus speeds up the manufacturing process. Fluid bed granulation is a multiple
-
step wet granulation process
performed

in the same vessel to pre
-
heat, granulate, and dry the powders. It is used because it allows close control of the
granulation process.

Dry granulation

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Dry granulation processes create granules by light compaction of the powder blend under low pressures. T
he compacts so
-
formed are broken up gently to produce granules (agglomerates). This process is often used when the product to be
granulated is sensitive to moisture and heat. Dry granulation can be conducted on a tablet press using slugging tooling or on

a

roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densificati
on
and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced. However, dry
granulation

often produces a higher percentage of fine granules, which can compromise the quality or create yield problems
for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be adde
d
to the formulatio
n to facilitate the formation of granules.

Granule lubrication

After granulation, a final lubrication step is used to ensure that the tableting blend does not stick to the equipment during

the
tableting process. This usually involves low shear blending of
the granules with a powdered lubricant, such as
magnesium
stearate

or
stearic acid
.

Manufacture of the tablets

Whatever process is used to make the tableting blend, the process of making a tablet by powder compaction is very similar.
First, the powder is filled into the die from above. The mass of powder is determined by the position of t
he lower punch in
the die, the cross
-
sectional area of the die, and the powder density. At this stage, adjustments to the tablet weight are
normally made by repositioning the lower punch. After die filling, the upper punch is lowered into the die and the p
owder is
uniaxially compressed to a porosity of between 5 and 20%. The compression can take place in one or two stages (main
compression, and, sometimes, pre
-
compression or tamping) and for commercial production occurs very fast (500

50 msec
per tablet). F
inally, the upper punch is pulled up and out of the die (decompression), and the tablet is ejected from the die by
lifting the lower punch until its upper surface is flush with the top face of the die. This process is simply repeated many t
imes
to manufact
ure multiple tablets.

Common problems encountered during tablet manufacturing operations include:

poor (low) weight uniformity, usually caused by uneven powder flow into the die

poor (low) content uniformity, caused by uneven distribution of the API in the

tableting blend

sticking of the powder blend to the tablet tooling, due to inadequate lubrication, worn or dirty tooling, and sub
-
optimal
material properties

capping, lamination or chipping. Such mechanical failure is due to improper formulation design or

faulty equipment
operation.

capping is also occurred due to high moisture content.

In the
tablet
-
pressing process, it is important that all ingredients be dry, powdered, and of uniform grain size
as much as
possible. The main guideline in manufacture is to ensure that the appropriate amount of active ingredient is equal in each
tablet so ingredients should be well
-
mixed. Compressed tablets are exerted to great pressure in order to compact the
mater
ial. If a sufficiently homogenous mix of the components cannot be obtained with simple mixing, 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 prepare powders for granulation into a tablet: wet gr
anulation and dry granulation.

Powders that can be mixed well do not require granulation and can be compressed into tablets through Direct Co
mpression


Direct Compression


This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of
the ingredients having to be changed. This

is not very common because many tablets have active pharamaceutical
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ingredients which will not allow for direct compression due to their concentration or the excipients used in formulation are
not conducive to direct compression.


Granulation is the proce
ss of collecting particles together by creating bonds between them. There are several different
methods of granulation. The most popular, which is used by over 70% of formulation in tablet manufacture is wet
granulation. Dry granulation is another method u
sed to form granules.


Wet granulation

for tablets

Wet granulation is a process of using a liquid binder or adhesive to the power mixture. The amount of liquid can be properly
managed, and overwett
ing will cause the granules to be too hard and underwetting will cause the granules to be too soft and
friable. Aqueous solutions have the advantage of being safer to deal with than solvents.


Proc
edure of Wet Granulation
for tablets

Step 1: Weighing and Blending
-

the active ingredient, filler, disintegration agents, are weighed and mixed.

Step 2: The wet granulate is prepared by adding the liquid binder/adhesive. Examples of binders/adhesives incl
ude aqueous
preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, CMC, gelatins, and
povidone. Ingredients are placed within a granulator which helps ensure correct density of the composition.

Step 3: Scre
ening the damp mass into pellets or granules

Step 4: Drying the granulation

Step 5: Dry screening: After the granules are dried, pass through a screen of smaller size than the one used for the wet mass

to select granules of uniform size to allow even fill
in the die cavity

Step 6: Lubrication
-

A dry lubricant, antiadherent and glidant are added to the granules either by dusting over the spread
-
out
granules or by blending with the granules. Its reduces friction between the tablet and the walls of the die cav
ity. Antiadherent
reduces sticking of the tablet to the die and punch.

Step 7:
Tableting
: Last step in which the tablet is fed into the die cavity and then compressed between a lower and an upper
punch.

Water may be used as the liquid binder, but sometimes many actives are not compatible with water. Water mixed into the
powder can form bonds between powder particles that are strong enough to lock them in together. However, once the water
dries, the

powders may fall apart and therefore might not be strong enough to create and hold a bond. Povidone also known
as polyvinyl pyrrolidone (PVP) is one of the most commonly used pharmaceutical binders. PVP and a solvent are mixed with
the powders to form a b
ond during the process, and the solvent evaporates. Once the solvent evaporates and powders have
formed a densely held mass, then the granulation is milled which results in formation of granules


D
ry granulation
for tablets

This process is used when the product needed to be granulated may be sensitive to moisture and heat. Dry granulation can
be conducted on a press using slugging tooling or on a roller compactor commonly referred to as a chilsonato
r. Dry
granulation equipment offers a wide range of pressure and roll types to attain proper densification. However the process may
require repeated compaction steps to attain the proper granule end point.


Process times are often reduced and equipment req
uirements are streamlined; therefore the cost is reduced. However, dry
granulation often produces a higher percentage of fines or noncompacted products, which could compromise the quality or
create yield problems for the tablet. It requires drugs or excipi
ents with cohesive properties.


Some granular chemicals are suitable for direct compression (free flowing) e.g. potassium chloride.

Tableting excipients with good flow characteristics and compressibility allow for direct compression of a variety of drugs.


Fluidized bed granulation


It is a multiple step process performed in the same vessel to pre
-
heat, granulate and dry the powders. It is today a commonly
used method in pharmaceuticals because it a
llows the individual company to more fully control the powder preparation
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process. It requires only one piece of machinery that mixes all the powders

and granules on a bed of air.


Tablet Compactio
n Simulator
Tablet formulations are designed and tested using a laboratory machine called a Tablet
Compaction Simulator or Powder Compaction Simulator. This is a computer controlled device that can measure the punch
positions, punch pressures, friction forc
es, die wall pressures, and sometimes the tablet internal temperature during the
compaction event. Numerous experiments with small quantities of different mixtures can be performed to optimise a
formulation. Mathematically corrected punch motions can be pr
ogrammed to simulate any type and model of production
tablet press. Small differences in production machine stiffness can change the strain rate during compaction by large
amounts, affecting temperature and compaction behaviour. To simulate true production

conditions in today's high speed
tablet presses, modern Compaction Simulators are very powerful and strong.


Initial quantities of active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator
reduces the amount of powd
er required for development.


Load controlled tests are particularly useful for designing multi
-
layer tablets where layer interface conditions must be
studied.
Pharm
aceutical Process Validation


Tablet compaction simulator

Tablet formulations are designed and tested using a laboratory machine called a Tablet Compaction Simulator or Powder
Compaction Simulator. This is a computer controlled device that can measure the
punch positions, punch pressures, friction
forces, die wall pressures, and sometimes the tablet internal temperature during the compaction event. Numerous
experiments with small quantities of different mixtures can be performed to optimise a formulation. M
athematically
corrected punch motions can be programmed to simulate any type and model of production tablet press. Initial quantities of
active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator reduces the amount of

powder required for product development.

Tablet presses


The tablet pressing operation

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An old Cadmach rotary tablet press

Tablet presses
, also called tableting machines, range
from small, inexpensive bench
-
top models that make one tablet at a
time (single
-
station presses), with only around a half
-
ton pressure, to large, computerized, industrial models (multi
-
station
rotary presses) that can make hundreds of thousands to millions

of tablets an hour with much greater pressure. The tablet
press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer. Common manufacturers of
tablet presses include Fette, Korsch, Kikusui, Manesty, IMA and Courtoy. Tabl
et presses must allow the operator to adjust the
position of the lower and upper punches accurately, so that the tablet weight, thickness and density can each be controlled.
This is achieved using a series of cams, rollers, and/or tracks that act on the ta
blet tooling (punches). Mechanical systems are
also incorporated for die filling, and for ejecting and removing the tablets from the press after compression. Pharmaceutical

tablet presses are required to be easy to clean and quick to reconfigure with diffe
rent tooling, because they are usually used
to manufacture many different products.

Tablet is a form of pharmaceutical dosage. It is made of active substances and
excipients, usually in powder form, pressed into a solid form. The excipients can include dil
uents, binders or granulating
agents, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to promote tablet break
-
up in the
digestive tract; sweeteners or flavours to enhance taste; and pigments to make the tablets visually at
tractive. A polymer
coating is often applied to make the tablet smoother and easier to swallow, to control the release rate of the active
ingredient, to make it more resistant to the environme
nt, or to enhance the tablet's.

The compressed tablet is the mos
t popular dosage form in use today. A tablet can be formulated to deliver an accurate
dosage to a specific site; it is usually taken orally. The tablet is just one of the many forms that an oral drug can take su
ch as
syrups, elixirs, suspensions, and emuls
ions. Medicinal tablets were originally made in the shape of a disk of whatever color
their components determined, but are now made in many shapes and colors to help distinguish different medicines. Tablets
could have marks with symbols, letters, and numbe
rs to be easily identified. Sizes of tablets range from a few millimeters to
about a centimeter.

The mechanical device that makes tablets is called a tablet press.

Generally the tablet press can produce lots of kinds of products in a form of tablet.

The gr
anulated product or powder from hopper comes to the die between two punches.

The punches then press together with a certain power and form a tablet. Firstly the lower punch comes down to create a
cavity in a die, and then the product comes to the die accor
ding to the depth of cavity. In the next step the excess of product
is scrapped away from the top of die. After that the upper punch goes down by a move of compression roll. The tablet is
ejected by lower pu
nch going up after compression.

There are two typ
es of tablet presses: single
-
punch tablet pre
sses and rotary tablet presses.

Rotary tablet presses can hold any number of punches and can produce up t
o one million tablets per hour.

Tablet presses that have two and more hoppers can produce multi
-
layered ta
blets.


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Tablet coating

Many tablets today are coated after being pressed. Although sugar
-
coating was popular in the past, the process has many
drawbacks. Modern tablet coatings are
polymer

and
polysaccharide

based, with
plasticizers

and
pigments

included. Tablet
coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during
the coating process, and must follow the fine contours of embossed characters or logos on ta
blets. Coatings are necessary for
tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also
useful to extend the shelf
-
life of components that are sensitive to moisture or oxidation. Specia
l coatings (for example with
pearlescent effects) can enhance brand recognition.

If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an
enteric coating

can be used, which
is resistant to
stomach

acid, and dissolves in the less acidic area of the intestines. Enteric coatings are also used for medicines
that can be nega
tively affected by taking a long time to reach the
small intestine
, where they are absorbed. Coatings are
often chosen to control the rate of dissolution of the drug in the g
astrointestinal tract. Some drugs will be absorbed better at
different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a
coating that dissolves quickly and easily in acid will be selected. If th
e rate of absorption is best in the large intestine or colon,
then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing.

There are two types of
coating machines

used in the pharmaceutical industry: coating pans and automatic coaters. Coating
pans are used mostly for sugar coating of pellets. Automatic coaters are used for all kinds of coatings; they can be equipped

with remote control
panel, dehumidifier, dust collectors. The explosion
-
proof design is required for alcohol containing
coatings.

The Tablet Coating Process

Many solid pharmaceutical dosage mediums are produced with coatings,

either on the external surface of tablets, or on
m
aterials dispensed within gelatine capsules. Coating serves a number of purposes:

Protects the tablet (or the capsule contents) from stomach acids

Protects the stomach lining from aggressive drugs such as enteric coated

aspirin

Provides a delayed release o
f the medication

Helps maintain the shape of the tablet

Ideally, the tablet should release the material gradually and the drug should be available for digestion beyond the stomach.
The coating can be specially formulated to regulate how fast the tablet dis
solves and where the active drugs are to be
absorbed into the body after ingestion.

Many factors can affect the end
-
use properties of pharmaceutical tablets:

Chemical composition

Coating process

Drying time

Storage and environmental monitoring

Coating Process Design & Control

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Tablet coating takes place in a controlled atmosphere inside a perforated rotating drum. Angled baffles fitted into the drum
and air flow inside the drum provide means of mixing the tablet bed. As a result, the tablets are

lifted and turned from the
sides into the centre of the drum, exposing each tablet surface to an even amount of deposited/sprayed coating.


The liquid spray coating is then dried onto the tablets by heated air drawn through the tablet bed from an inlet
fan. The air
flow is regulated for temperature and volume to provide controlled drying and extracting rates, and at the same time,
maintaining the drum pressure slightly negative relative to the room in order to provide a completely isolated process
atmosp
here for the operator.


Tablet coating equipment may include spray guns, coating pan, polishing pans, solution tanks, blenders and mixers,
homogenizers, mills, peristaltic pumps, fans, steam jackets, exhaust and heating pipes, scales and filters. Tablet co
ating
processes may include sugar coating (any mixtures of purified water, cellulose derivatives, polyvinyl, gums and sugar) or fil
m
coating (purified water, cellulose derivatives).

The coating process is usually a batch driven task consisting of the follo
wing phases:

Batch identification and Recipe selection (film or sugar coating)

Loading/Dispensing (accurate dosing of all required raw materials)

Warming

Spraying (application and rolling are carried out simultaneously)

Drying

Cooling

Unloading

A control s
ystem must therefore provide flexibility in the way in which accurate and repeatable control of the coating
environment is achieved and will include the following features:

Precise loop control with setpoint profile programming

Recipe Management System for

easy parameterization

Sequential control for complex control strategies

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Secure collection of on
-
line data from the coating system for

analysis and evidence

Local operator display with clear graphics and controlled access to parameters

The Eycon
TM

Visual S
upervisor is an ideal solution for the

tablet coating

process.

Tablet coating


After being produced many tablets require to be coated. In the past was popular sugar coating but now more tablets are
coated with polymer, polysaccharide and alcohol based
solutions which include different pigments and plasticizers.

There are many reasons for coating of tablets:



-


Suppression of unpleasant taste

-


Easy swallowing

-


Extending the expiration date of sensitive to oxygen and moist
ure components

-


Embossing the special characters or logo

-


Control of dissolution of ingredients in the digestive tract

To suit all its purposes coating must be resistant and prevent tablets from sticking.



There are two types of coat
ing machines: automatic coaters and coating pans.

Coating pans are simple machines and they are mainly used for sugar coatings of round
-
shaped tablets and pellets.

Automatic coaters are used for all kinds of coatings, including enteric coatings. They can b
e equipped with solution
preparation system, dust collectors, air treatment units etc. The explosion
-
proof design is available for alcohol
-
based
coatings.


Picking and sticking


This is when the coating removes a piece of the tablet from the core. Overwe
tting or examples or excessive film tackiness
causes tablets to stick to each other or to the coating pan. On drying, at the point of contact, a piece of the film may rema
in
adhered to the pan or to another tablet, giving a “picked” appearance to the table
t surface and resulting in a small exposed
area of the core. It is caused by over
-
wetting the tablets, by under
-
dr
ying, or by poor tablet quality

REMEDY:

A reduction in the liquid application rate or increase in the drying air temperature and air volume usually solves this
problem. Excessive tackiness may be an indication of a poor formulation.


Twinning

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This is the term for two tablets that stick toget
her, and it’s a common problem with capsule shaped tablets.

REMEDY :
Assuming you don’t wish to change the tablet shape, you can solve this problem by balancing the pan speed and
spray rate. Try reducing the spray rate or increasing the pan speed. In some
cases, it is necessary to modify the design of the
tooling by very slightly changing the radius. The change is almost impossible to see, but it prevents the twinning problem.


Color Variation

This problem can be caused by processing conditions or the formu
lation. Improper mixing, uneven spray pattern and
insufficient coating may result in color variation. The migration of soluble dyes, plasticizers and other additives during dr
ying
may give the coating a mottled or spotted appearance.

REMEDY:

1. The use of

lake dyes eliminates dye migration.

2. A reformulation with different plasticizers and additives is the best way to solve film instabilities caused by the ingred
ients.


Orange Peel


This refers to a coating texture that resembles the surface of an oran
ge. Inadequate spreading of the coating solution before
drying causes a bumpy or “orange
-
peel” effect on the coating.

It is usually the result of high atomization pressure in combination with spray rates that are too high. This also indicates
that
spreadi
ng is impeded by too rapid drying or by high solution viscosity.

REMEDY:
Thinning the solution with additional solvent may correct this problem.


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 specification.


Capping and Lamination



This is when the tablet separates in laminar fashion. Capping is partial or complete separation of top or bottom crowns of
tablet main
body. Lamination is separation of a tablet into two or more distinct layers. Friability test can be

used to reveal
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these problems

The problem stems from improper tablet compression, but it may not reveal itself until you start coating. How you operate
the
coating system, however, can exacerbate the problem.

REMEDY :

Be careful not to over
-
dry the tablets in the preheating stage. That can make the tablets brittle and promote
capping.



Roughness


A rough or gritty surface is a defect often observed when coa
ting is applied by a spray. Some of the droplets may dry too
rapidly before reaching the tablet bed, resulting in the deposits on the tablet surface of “spray dried” particles instead of

finely divided droplets of coating solution. Surface roughness also i
ncreases with pigment concentration and polymer
concentration in the coating solution.

REMEDY:

Moving the nozzle closer to the tablet bed and reducing the degree of atomization can decrease the roughness due
to “spray drying”.


Hazing / Dull Film

This is
sometimes called Bloom. It can occur when too high a processing temperature is used for a particular formulation.
Dulling is particularly evident when cellulosic polymers are applied out of aqueous media at high processing temperatures. It

can also occur i
f the coated tablets are exposed to high humidity conditions and partial salvation of film results.


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. During drying, the film may shrink and pull away from the sharp corners of an intagliation or bisect,
resulting in a “brid
ging” of the surface. This defect can be so severe that the monogram or bisect is completely obscured.

REMEDY:

Increasing the plasticizer content or changing the plasticizer can decrease the incidence of bridging.


Filling

Filling is caused by applying to
o much solution, resulting in a thick film that fills and narrows the monogram or bisect. In
addition, if the solution is applied too fast, Overwetting may cause the liquid to quickly fill and be retained in the monogr
am.

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REMEDY:
Judicious monitoring of th
e fluid application rate and thorough mixing of the tablets in the pan can
prevent filling.



Erosion



This can be the result of soft or friable tablets (and the pan turning too fast), an over
-
wetted tablet surface, inadequate
drying, or lack of tablet s
urface strength.


Peeling and frosting

This is a defect where the coating peels away from the tablet surface in a sheet. Peeling indicates that the coating solution

did not lock into the tablet surface. This could be due to a defect in the coating solution
, over
-
wetting, or high moisture
content in the tablet core which prevented the coating to adhering.


Chipping

This is the result of high pan speed, a friable tablet core, or a coating solution
that lacks a good plasticizer


Blistering

When coated tablets

require further drying in ovens, too rapid evaporation of the solvent from the core and the effect of high
temperature on the strength, elasticity and adhesion of the film may result in blistering.

REMEDY:

Milder drying conditions are warranted in this ca
se.


Cracking

It occurs if internal stresses in the film exceed the tensile strength of the film.

REMEDY: tensile strength of the film can be increased by Using higher molecular weight polymers or polymer blends.

Pill
-
splitters

It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored,
but there are devices called
pill
-
splitters

which cut unscored and scored tablets. Tablets with special coatings (for
example enteric coatings or controlled
-
release coatings) should not be broken before use, as this will expose the
tablet core to the digestive juices, circumventing the intended del
ayed
-
release effect.

Evaluation of tablet

1. General Appearance:

The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lo
t
-
to
-
lot uniformity and tablet
-
to
-
tablet uniformity. The control o
f general appearance involves the measurement of size, shape,
color, presence or absence of odor, taste etc.

2. Size & Shape:

It can be dimensionally described & controlled. The thickness of a tablet is only variables. Tablet thickness can be measured

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

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3. Unique identification marking:

These marking utilize some form of embossing, engraving or printing. These markings include company name or s
ymbol,
product code, product name etc.

4. Organoleptic properties:

Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against
standard color.

5. Hardness:

Tablet requires a certain amount of stren
gth or hardness and resistance to friability to withstand mechanical shakes of
handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength.

6.

Friability:

Friability of a tablet can determine in laboratory by R
oche friabilator. This consist of a plastic chamber that revolves at 25
rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operate for 100 revolutions. The

tablets are reweighed. Compress tablet that lose less than

0.1 to 0.5 % of the Tablet weigh are consider acceptable.

7. Weight Variation test (U.S.P.):

Take 20 tablet and weighed individually. Calculate average weight and compare the individual tablet weight to the average.
The tablet pass the U.S.P. test if no m
ore that 2 tablets are outside the percentage limit and if no tablet differs by more than
2 times the percentage limit.

8. Content Uniformity Test:

Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of the 10 table
ts must contain not
less than 85% and not more than 115% of the labeled drug content and the 10th tablet may not contain less than 75% and
more than 125% of the labeled content.

If these conditions are not met, remaining 20 tablet assayed individually and
none may fall out side of the 85 to 115% range.

9. Disintegration Test (U.S.P.):

The U.S.P. device to test disintegration uses 6 glass tubes that are 3” long; open at the top and 10 mesh screen at the botto
m
end. To test for disintegration time, one table
t is placed in each tube and the basket rack is positioned in a 1
-
L beaker of
water, simulated gastric fluid or simulated intestinal fluid at 37 ± 20 C such that the tablet remain 2.5 cm below the surfac
e of
liquid on their upward movement and not closer t
han 2.5 cm from the bottom of the beaker in their 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 perforate
d plastic discs on each tablet.

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

Disintegration time: Uncoated tablet: 5
-
30 mi
nutes

Coated tablet: 1
-
2 hours

10.

Dissolution

Test:

A) Apparatus
-
1 (Basket Type):

A single tablet is placed in a small wire m
esh basket attached to the bottom of the shaft
connected to a variable speed motor. The basket is immersed in a
dissolution

med
ium (as specified in monograph) contained
in a 1000 ml flask. The flask is cylindrical with a hemispherical bottom. The flask is maintained at 37±0.50C by a constant
temperature bath. The motor is adjusted to turn at the specified speed and sample of the f
luid are withdrawn at intervals to
determine the amount of drug in solutions.

B) Apparatus
-
2 (Paddle Type ):

It is same as apparatus
-
1, except the basket is replaced by a paddle. The dosage form is
allowed to sink to the bottom of the flask before stirrin
g. For dissolution test U.S.P. specifies the dissolution test medium and
volume, type of apparatus to be used, rpm of the shaft, time limit of the test and assay procedure for.

The test tolerance is expressed as a % of the labeled amount of drug dissolved
in the time limit.

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The quantitative evaluation and assessment of a tablet‘s chemical, physical and bioavailability properties are important in t
he
design of tablets and to monitor product quality. These properties are important since chemical breakdown or

interactions
between tablet components may alter the physical tablet properties, and greatly affect the bioavailability of the tablet
system.

General

appearance of tablets, its visual identity and overall ‘elegance’ is essential for consumer acceptance, control of lot
-
to
-
lot uniformity and general tablet
-
to
-
tablet uniformity and for monitoring the production process. The control of general
appearance i
nvolves measurement of attributes such as a tablet’s size, shape, color, presence or absence of odour, taste,
surface textures, physical flaws and consistency.

Tablets Size and shape


The shape and dimensions of compressed tablets are determined by the ty
pe of tooling during the compression process. At a
constant compressive load, tablets thickness varies with changes in die fill, particle size distribution and packing of the
powder mix being compressed and with tablet weight, while with a constant die fil
l, thickness varies with variation in
compressive load. Tablet thickness is consistent from batch to batch or within a batch only if the tablet granulation or powd
er
blend is adequately consistent in particle size and particle size distribution, if the pun
ch tooling is of consistent length, and if
the tablet press is clean and in good working condition.

The thickness of individual tablets may be measured with a micrometer, which permits accurate measurements and provides
information of the variation betwee
n tablets. Tablet thickness should be controlled within a ±5% variation of a standard
value. Any variation in thickness within a particular lot of tablets or between manufacturer’s lots should not be apparent to

the unaided eye for consumer acceptance of t
he product. In addition, thickness must be controlled to facilitate packaging.

The physical dimensions of the tablet along with the density of the material in the tablet formulation and their proportions,

determine the weight of the tablet. The size and s
hape of the tablet can also influence the choice of tablet machine to use,
the best particle size for granulation, production lot size that can be made, the best type of tableting processing that can
be
used, packaging operations, and the cost of productio
n.

The
USP

has provided limits for the average weight of uncoated compressed tablets. These are applicable when the tablet
contains 50mg or more of the drug substance or when the
latter comprises 50% or more, by weight of the dosage form.
Twenty tablets are weighed individually and the average weight is calculated. The individual tablet weights are then
compared to the average weight. Not more than two of the tablets must differ fr
om the average weight by not more than the
percentages stated in Table 1. No tablet must differ by more than double the relevant percentage. Tablets that are coated
are exempted from these requirements but must conform to the test for content uniformity if

applicable
3
.



Average weight



Percent difference

130mg or less

10

More than 130mg through 324mg

7.5

More than 324mg

5

Weight variation requirements

Organoleptic properties

Color is a vital means of identification for many pharmaceutical tablets and is also usually important for consumer
acceptance. The color of the product must be uniform within a single tablet, from tablet to tablet and from lot to lot. Non
uniformity of co
loring not only lack esthetic appeal but could be associated by the consumer with non uniformity of content
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and general poor product quality. Non uniformity of coloring is usually referred to as mottling. The eye cannot differentiate

small differences in c
olor nor can it precisely define color and efforts have been made to quantitate color evaluations.
Reflectance spectrophotometry, tristimulus colorimetric measurements and micro reflectance photometer have been used to
measure color uniformit
y and gloss on

a tablet surface

.

Odor may also be important for consumer acceptance of tablets and can provide an indication of the quality of tablets as the
presence of an odor in a batch of tablets could indicate a stability problem, such as the characteristic odor
of acetic acid in
degrading aspirin tablets. However, the presence of an odor may be characteristic of the drug (e.g. vitamins), added
ingredients (e.g. flavoring agent) or the dosage form (e.g. film
-
coated tablets).

Taste is also important for consumer a
cceptance of certain tablets (e.g. chewable tablets) and many companies utilize taste
panels to judge the preference of different flavors and flavor levels in the development of a product. Taste preference is
however subjective and the control of taste in
the production of chewable tablets is usually based on the presence or
absence of a specified taste.

Content Uniformity Test For Tablets

The content uniformity test is used to ensure that every tablet contains the amount of drug substance intended with li
ttle
variation among tablets within a batch. Due to increased awareness of physiological availability, the content uniformity test

has been included in the monographs of all coated and uncoated tablets and all capsules intended for oral administration
wher
e the range of size of the dosage form available include 50mg or smaller sizes. Tablet monographs with a content
uniformity requirement do not have weight variation requirements
4
. For content uniformity test, representative samples of
30tablets are selec
ted and 10 are assayed individually. At least 9must assay within ±15% of the declared potency and none
may exceed ±25%.

The variability of dosage form (solid) is controlled and assessed by the content uniformity tests. It is recommended to go fo
r a
random

sampling.

The size range of the dosage form is less than or equal to 50mg

Tablets:

30 units are kept aside.

10 tablets are assayed.

Results are interpreted as follows

All tablets
-

85%
-
115%
-

RSD</= 6

If the above condition is not achieved, the results
should be as follows inorder to pass the test

Percentage purity should be within 75%
-
125%

20 tablets (remaining) are assayed.

Out of 30 tablets, 1 tablet can be outside 85
-
115%

Not even one should be above 75%
-
125%

RSD</= 7.8%

Capsules:

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10 capsules are ta
ken and subjected to assay.

They will pass the test if

All capsules
-

85%
-
115%
-

RSD</= 6

If the above condition is not satisfied still they can pass the test under following conditions

Percentage purity should be within 75%
-
125%

20 tablets (remaining) are
assayed.

Out of 30 tablets, <3 tablets can be outside 85
-
115%

Not even one should be above 75%
-
125%

RSD<7.8%

Mechanical strength of tablets

The mechanical strength of a tablet provides a measure of the bonding potential of the material concerned and this

information is useful in the selection of
excipients
. An excessively strong bond may prevent rapid disintegration and
subsequent
dissolution

of a drug. Weak bonding characteristics may limit the selection and/or proportion of
excipients
, such
as lubricants, that would be added to the formulation.

The mechanical properties of pharmaceutical tablets are quantifiable by the fr
iability, hardness or crushing strength
, crushing
strength
-
friability values, tensile
strength

and brittle fracture Index

.

Friability Test

for Tablets


Friction and shock are the forces that most often cause tablets to chip, cap or break. T
he
friability test

is closely related to
tablet hardness and is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling

and
shipping. It is usually measured by the use of the Roche friabilator. A number of tablets are weighed and placed in the
apparatus where they are exposed to rolling and repeated shocks as they fall 6 inches in each turn within the apparatus. Afte
r
four

minutes of this treatment or 100 revolutions, the tablets are weighed and the weight compared with the initial weight.
The loss due to abrasion is a measure of the tablet friability. The value is expressed as a percentage. A maximum weight loss

of not mor
e than 1% of the weight of the tablets being tested during the friability test is considered generally acceptable and
any broken or smashed tablets are not picked up
3
. Normally, when capping occurs, friability values are not calculated. A
thick tablet ma
y have less tendency to cap whereas thin tablets of large diameter often show extensive capping, thus
indicating that tablets with greater thickness have reduced internal stress.

Hardness or Crushing strength of Tablets

The resistance of tablets to
capping
, abrasion or breakage under conditions of storage, transportation and handling before
usage depends on its
hardness
. The small and portable
hardness tester

was manufactured and introduced by Monsanto in
the Mid 1930s. It is now designated as either the Mo
nsanto or Stokes hardness tester. The instrument measures the force
required to break the tablet when the force generated by a coil spring is applied diametrally to the tablet. The Strong
-
Cobb
Pfizer and Schleuniger apparatus which were later introduced me
asures the diametrically applied force required to break the
tablet.

Hardness, which is now more appropriately called crushing strength determinations are made during tablet production and
are used to determine the need for pressure adjustment on tablet ma
chine. If the tablet is too hard, it may not disintegrate in
the required period of time to meet the
dissolution

specifications
; if it is too soft, it may not be able to withstand the handling
during subsequent processing such as coating or packaging and shipping operations. The force required to break the tablet is
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measured in kilograms and a crushing strength of 4Kg is usually c
onsidered to be the m
inimum for satisfactory tablets
. Oral
tablets normally have a hardness of 4 to 10kg ; however, hypodermic and chewable tablets are usually much softer ( 3 kg )
and some sustained release tablets are much harder (10
-
20 kg ).
Tablet
hardness

have been associated with other tablet
properties such as density and porosity. Hardness generally increase with normal storage of tablets and depends on the
shape, chemical properties, binding agent and pressure applied during compression.

Anoth
er measure of the mechanical strength of pharmaceutical tablets that have been used is the
crushing strength
-
friability
ratio

(CSFR). The CS provides a measure of tablet strength while F is a measure of tablet weakness. Studies have shown that
the higher t
he CSFR values, the stronger the tablet.

Tensile strength

A non
-
compendial method of measuring the mechanical strength of tablets that is now widely used is the tensile strength.
This is the force required to break a tablet in a diametral compression test. The radial tensile strength, T, of the tablets
can be
cal
culated from the equation:

T = 2 F / p d H (1)

where F is the load needed to break the tablet, and d and H are the diameter and thickness respectively. Several precautions
must be taken when using the equation. Various factors e.g. test conditions, defor
mation properties of the material,
adhesion conditions between compact and its support and tablet shape may influence the measu
rements of the tensile
strength
.

Some authors have suggested the determination of axial tensile strength because of the sensitiv
ity of the radial tensile
strength measurements
to crack propagation variations
. The axial tensile strength (T
x
) can be calculated from the following
relationship:

T
x
= 4 F / p d
2
(2)

Tensile strength has been used in combination with indentation har
dness to evaluate tabletting performance of materials.
The indentation hardness is a time
-
dependent property used to measure the plastic yield of a material. It can be determined
by either static methods (e.g. the Brinell, Vickers and Rockwell hardness tes
ts) or the dynamic methods. The static
indentation methods involve the formation of a permanent indentation on the surface of the material tested and the
hardness is determined by means of the load applied and the size of the indentation formed. In the dyn
amic indentation
tests, either a pendulum is allowed to strike from a known distance or an indenter is allowed to fall under gravity unto the
surface of the test material. The hardness is then determined from the rebound height of the pendulum or the volum
e of the
resulting indentation. Using an apparatus consisting of a steel sphere pendulum acting
as an indenter, Hiestand et al

estimated the hardness (i. e. the mean deformation pressure) of compacted materials by dividing the energy consumed
during the im
pact by the volume of indentation.

Brittle fracture index (BFI)

Hiestand et al

have studied the effects of decompression on the tabletting performance of pharmaceutical materials and
stated that whether or not fracture occurs during the shear deformation

which accompanies decompression depends on the
ability of the materials to relieve stresses by plastic deformation without undergoing brittle fracture and this ability is a

time
-
dependent phenomenon. Those materials that relieve stress rapidly are less li
kely to cap or laminate. The brittleness test is
based on the Griffith fracture theory which teaches that, for crack growth to occur, the energy stored at the tip of a crack
must just exceed the energy required to form two new surfaces resulting from the p
ropagation of the crack. Also, the amount
of energy stored at the tip of a crack is a function of the dimensions of the crack.

In the light of this theory, Hiestand et al

showed that when compacts are made with a small axially
-
oriented round hole at
their

centre, the compact is nearly always weakened. Under the conditions of the tensile strength test, elasticity theory
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predicts that the stress concentration factor for the hol
e should be about 3.0. Hiestand

showed that for isotropic materials,
the ratio of
compressive stress at the centre of a compact to the tensile stress, which causes fracture, has a value of 3.7.
However, recent studies have shown that for a ratio of hole diameter to disc of about 0.1, the stress concentration factor, i
.e.
the ratio betwe
en tensile stress at the inner boundary of the hole and the tensile stress of a tablet having no hole, should be
around 10.

Thus, the BFI is obtained by comparing the tensile strength of tablets with a hole at their centre, which acts as a built
-
in stress

concentration defect, with the tensile strength of tablets without a hole, both at the same relative density. The brittle
fracture index (BFI) of the tablets was calculated using the following equation

BFI = [(T / T
o
)


1 (3)

Where T is the tensile st
rength of the tablet without a hole and T
o
, to the tensile strength of a tablet with a hole. The
theoretical value of BFI range is 0
-

1 when the stress concentration factor is 3. Since the BFI is an inverse measure of localized
stress relief, it should
indicate the tendency of a tablet to laminate or cap. In principle, BFI values in excess of unity may
occur. In practice, however, one probably cannot make an intact tablet of a material with a BFI of 1. Therefore, the observed

range of values may not exce
ed the 0
-

1 range. Where by the closer the value of BFI to 0, the less stress relief takes place. A
high value of BFI is an indication of the tendency of the tablet to laminate during the compaction process. A low BFI value i
s
desirable for minimal lamina
tion and capping during production.

Robert and Rowe

extended the determination of the BFI to compact of ‘tablet
-
sized’ dimensions. This allows the BFI to be
measured at strain rates and conditions approaching those normally used in tabletting. They found
the BFI values for
microcrystalline cellulose, tablettose and heavy magnesium carbonate to be in good agreement with the results of previous
workers. Itiola & Pilpel using both granular and powdered metronidazole formulations studied the mechanical propert
ies of
the tablets and differentiated between the bond strength of the tablets as measured by their tensile strength and the
tendency of the tablets to laminate or cap as measured by the brittle fracture index values. They found that tablets made
from gran
ules had lower tensile strength than those made from powders but were also less brittle.

The BFI have also been used to characterize the mechanical properties

of pharmaceutical formulations

and some local
starches, namely cassava, potato and yam starches.

Tablets of these starches were shown to possess low tensile strength
values, but also had low BFI values. Studies have also shown that the BFI is affected by the nature and concentration of
binding agent, compression pressure and compression speed. Genera
lly, the higher the BFI values, the more friable a tablet is
likely to be.

Tablet Disintegration


For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first
important step toward this conditio
n is usually the break
-
up of the tablet; a process known as disintegration. The
disintegration test
is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into
particles which will pass through a 10 mesh screen. Generally, the test is useful as a quality assurance tool for conventiona
l
dosage forms. The
disintegration test
is carried out using the disintegration tester which consists of a basket rack holding 6
plastic tubes, open at the top and bottom, the bott
om of the tube is covered by a 10
-
mesh screen. The basket is immersed in
a bath of suitable liquid held at 37
o
C, preferably in a 1L beaker. For compressed uncoated tablets, the testing fluid is usually
water at 37
o
C but some monographs direct that simu
lated gastric fluid be used. If one or two tablets fail to disintegrate, the
test is repeated using 12 tablets. For most uncoated tablets, the BP requires that the tablets disintegrate in 15minutes
(although it varies for some uncoated tablets) while for c
oated tablets, up to 2hours may be required. The individual drug
monographs specify the time disintegration must occur to meet the Pharmacopoeial standards.

In the past, the only release index required for a tablet was its disintegration time which does n
ot necessarily measure the
physiological availability of the drug in a patient. Studies have shown that the agitation of the gastric contents during nor
mal
contractions is quite mild in contrast to the turbulent agitation produced in the
disintegration test
appara
t
us. The low order
magnitude of agitation in the stomach produces substantially higher disintegration in vivo than those obt
ained using the
USP

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apparatus. Furthermore, the particles of the disintegrated tablets are not dispersed throughout the stomach but remains as
an aggregate. Thus, the tablet
disintegration test
is limited to manufacturing control of lot
-
to
-
lot variations in individual
products and is not a measure of bioavailab
ility. Nevertheless, it is used to provide a simple and useful means for monitoring
and controlling the quality of tablets.

Theories of disintegration of Tablets

Several mechanisms of tablet disintegration have been proposed. Some of these are given belo
w. Even though these
concepts are listed separately, inter
-
relationships probably occur in almost all tablet formulations.

(i) Evolution of gas

If a gas is evolved by a chemical reaction when the tablet comes into contact with water, then the tablet will

disintegrate.
This is the basis for the manufacture of effervescent tablets. An example of such a reaction is of sodium bicarbonate with
citric and tartaric acids, which yields carbon dioxide. Peroxides incorporated in certain formulations decompose in th
e
presence of oxygen and this also causes disi
ntegration
.

(ii) Heat of wetting


The heat produced when a tablet is immersed in water causes the entrapped air in the tablet to expand and exert sufficient
pressure to disintegrate the tablet.

(iii) Effect o
f water absorption

The water absorbed by the tablet initiate disintegration, but this depends on the solubility of the dru
g and other ingredients
present
.

(iv) Swelling

The grains of the disintegrant, particularly of starches, swell in the presence of w
ater and exert pressure on the gra
nules to
force them apart
. Shangraw et al

reported that tablets of water insoluble drugs disintegrated faster with starches than those
of water soluble drugs due to the diminished water absorption capacity of the starches
in the latter case.

(v) Porosity of tablets

It has been shown that penetration of water into a tablet is proportional to its mean pore diameter or porosity. The porosity

and permeability of tablets decrease as the tabletting pressure is increased, and as

the porosity decreases, the disintegration
time increases

. Though no quantitative relationships have been reported between disintegration and penetration times,
generally short disintegration times are associat
ed with rapid fluid penetration
.

Purpose

D
isintegration tests are performed as per the pharmacopoeial standards. Disintegration is a measure of the quality of the oral

dosage form like tablets and capsules. Each of the pharmacopoeia like the
USP
, BP, IP etc each have their own set of
standards and specify disintegration tests of their own.
USP
, European pharmacopoeia and Japanese pharmacopoeia have
been harmonised by the International conference on Harmonisation (
ICH
) and are interchangeable.

The disintegration test is performed to find out the time it takes for a solid oral dosage form

like a tablet or capsule to
completely disintegrate. The time of disintegration is a measure of the quality. This is because, for example, if the
disintegration time is too high; it means that the tablet is too highly compressed or the capsule shell gelat
in is not of
pharmacopoeial quality or it may imply several other reasons. And also if the disintegration time is not uniform in a set of
samples being analysed, it indicates batch inconsistency and lack of batch uniformity.

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Disintegration Test Apparatus

Coming to the test, the disintegration test is conducted using the disintegration apparatus. Although there are slight
variations in the different pharmacopoeias, the basic construction and the working of the apparatus remains the same. The
apparatus cons
ists of a basket made of transparent polyvinyl or other plastic material. It has 6 tubes set into the same basket
with equal diameter and a wire mesh made of stainless steel with uniform mesh size is fixed to each of these six tubes. Small

metal discs may
be used to enable immersion of the dosage form completely. The entire basket
-
rack assembly is movable by
reciprocating motor which is fixed to the apex of the basket
-
rack assembly. The entire assembly is immersed in a vessel
containing the medium in which
the disintegration test is to be carried out. The vessel is provided with a thermostat to
regulate the temperature of the fluid medium to the desired temperature.

Disintegration Test Method

The disintegration test for each dosage form is given in the pha
rmacopoeia. There are some general tests for typical types of
dosage forms. However, the disintegration test prescribed in the individual monograph of a product is to be followed. If the
monograph does not specify any specific test, the general test for th
e specific dosage form may be employed. Some of the
types of dosage forms and their disintegration tests are:

1.Uncoated tablets
-

Tested using distilled water as medium at 37+/
-
2 C at 29
-
32 cycles per minute; test is completed after 15
minutes. It is accep
table when there is no palpable core at the end of the cycle (for at least 5 tablets or capsules) and if the
mass does not stick to the immersion disc.

2.Coated tablets
-

the same test procedure is adapted but the time of operation is 30 minutes.

3.Enteric
coated/ Gastric resistant tablets
-

the test is carried out first in distilled water (at room temperature for 5 min.; USP
and no distilled water per BP and IP), then it is tested in 0.1 M HCL (upto 2 hours; BP) or Stimulated gastric fluid (1 hour;

USP)
foll
owed by Phosphate buffer, pH 6.8 (1 hour; BP) or Stimulated intestinal fluid without enzymes (1 hour; USP).

4.Chewable tablets
-

exempted from disintegration test (BP and IP), 4 hours (USP).

These are a few examples for illustration. The disintegration test
s for capsules, both hard and soft gelatin capsules are also
performed in a similar manner. Also, the USP also provides disintegration tests for suppositories, pessaries etc.

Applications of Disintegration test
:

1.

Disintegration test is a simple test wh
ich helps in the preformulation stage to the formulator.

2.

It helps in the optimisation of manufacturing variables, such as compressional force and dwell time.

3.

This test is also a simple in
-
process control tool to ensure uniformity from batch to batch
and among different tablets

4.

It is also an important test in the quality control of tablets and hard gelatine capsules.

Advantages of Disintegration tests
:

This test is simple in concept and in practice.

It is very useful in preformulation, optimisation
and in quality control.

Disadvantages:

Disintegration test cannot be relied upon for the assurance of bioavailability.

Books for further studying Disintegration test

1.The Theory and practice of Industrial Pharmacy by Leon Lachman and Herbert A. Lieberman
, CBS Publishers and
distributors, New Delhi.

2.Pharmaceutical Dissolution Testing, edited by Jennifer Dressman and Johannes Kramer, Taylor & Francis publications

3.Pharmaceutical Dosage Forms and Drug Delivery Systems by Howard C. Ansel, Loyd V. Allen, Jr
.,and Nicholas G.Popovich;
Seventh Edition, Lippincott Williams & Wilkins publishers.

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FORMULATION

INDIAN PHARMACOPOEIA

1996 (IP)

BRITISH PHARMACOPOEI
A 2009 (BP)

UNITED STATES PHARMA
COPOEIA
2009 (
USP
)

Hard gelatin
capsules

Uses disintegration apparatus with
250ml or 1 L of specified medium at
37+
-
2
O
C & for specified time as per
monograph. If 1
-
2 fail, repeat for 12
different units. 16 out of 18 indicate
test is affirmative.

Uses
disintegration apparatus with
water R or specified liquid medium,
add a metal disc to prevent capsule
from floating & operate for 30 min. or
as per monograph. If 1
-
2 fail, repeat for
12 different units. 16 out of 18 indicate
test is affirmative.

Same as un
coated tablets. Use a
circular cloth mesh of diameter 0.60
-
0.655mm & 1.8
-
2.2mm square mesh
size. No palpable material to remain
on the mesh.

Soft gelatin capsules

Uses disintegration apparatus with
250ml or 1 L of specified medium at
37+
-
2
O
C & for
specified time as per
monograph. If 1
-
2 fail, repeat for 12
different units. 16 out of 18 indicate
test is affirmative.

Uses disintegration apparatus with
water R or specified liquid medium,
add a metal disc to prevent capsule
from floating & operate for 3
0 min. or
as per monograph. If 1
-
2 fail, repeat for
12 different units. 16 out of 18 indicate
test is affirmative.

Same as uncoated tablets. Use a
circular cloth mesh of diameter 0.60
-
0.655mm & 1.8
-
2.2mm square mesh
size. No palpable material to remain
on
the mesh.

Modified release
capsules

Disintegration test
not applicable

Disintegration test
not applicable

Disintegration test
not applicable

Gastro resistant
capsules

Uses disintegration apparatus with
250ml or 1 L of
specified medium at
37+
-
2
O
C & for specified time as per
monograph. If 1
-
2 fail, repeat for 12
different units. 16 out of 18 indicate
test is affirmative.

Uses disintegration apparatus with 0.1
M HCl at 37+
-
2
O
C for 2
-
3 hrs (nlt 1
hour), if there is no crack
ing or
breaking, continue with phosphate
buffer, pH 6.8 at same temperature for
1 hour or as per monograph. If 1
-
2 fail,
repeat for 12 different units. 16 out of
18 indicate test is affirmative.

-
NA
-

Suppositories

Uses disintegration apparatus for
suppos
itories/pessaries Uses 4 L of
specified medium at 37+
-
2
O
C & for
specified time as per monograph. If 1
-
2 fail, repeat for 12 different units. 16
out of 18 indicate test is affirmative.

Uses disintegration apparatus with
water R or specified liquid medium &
for 30 min. for suppositories with fatty
base and for 60 min. for suppositories
with water soluble base. If 1
-
2 fail,
repeat for 12 different units. 16 out of
18 indicate test is affirmative.

-
NA
-

Rectal capsules

-
NA
-



-
NA
-

Uncoated tablets

Uses
disintegration apparatus with
250ml or 1 L of specified medium &
for specified time as per monograph.
If 1
-
2 fail, repeat for 12 different
units. 16 out of 18 indicate test is
affirmative.

Uses disintegration apparatus Uses
liquid medium water R or specifi
ed
medium for 15 min. If 1
-
2 fail, repeat
for 12 different units. 16 out of 18
indicate test is affirmative.

Uses disintegration apparatus with
specified liquid medium & for
specified time as per monograph. If 1
-
2 fail, repeat for 12 different units. 16
ou
t of 18 indicate test is affirmative.

Chewable tablets

-
NA
-

Disintegration test
not applicable.

Same as uncoated tablets. Uses
disi
ntegration apparatus with specified
liquid medium & for 4 hours or as per
monograph. If 1
-
2 fail, repeat for 12
different units. 16 out of 18 indicate
test is affirmative.

Non
-
film coated
tablets

-
NA
-

Uses disintegration apparatus with
water R or specified liquid medium &
for 60 min., if there is no cracking of
coat; continue by replacing the
medium with 0.1 M HCl for specified
time as per monograph. If 1
-
2 fail,
repeat for 12 different units. 16 out of

Same as uncoated tablets. Uses
disintegration apparatus with specified
liquid medium & for specified time as
per monograph. If 1
-
2 fail, repeat for
12 different units. 16 out of 18
indicate test is affirmative.

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18 indicate test is affirmative.

Film coate
d tablets

-
NA
-

Uses disintegration apparatus with
water R or specified liquid medium &
for 30 min., if there is no cracking of
coat; continue by replacing the
medium with 0.1 M HCl for specified
time as per monograph. If 1
-
2 fail,
repeat for 12 different u
nits. 16 out of
18 indicate test is affirmative.

Same as uncoated tablets. Uses
disintegration apparatus with specified
liquid medium & for specified time as
per monograph. If 1
-
2 fail, repeat for
12 different units. 16 out of 18
indicate test is affirmati
ve.

Gastro resistant
tablets (Enteric
Coated)

Uses disintegration apparatus with
250ml or 1 L of specified medium &
for specified time as per monograph.
If 1
-
2 fail, repeat for 12 different
units. 16 out of 18 indicate test is
affirmative.

Uses
disintegration apparatus with 0.1
M HCl at 37+
-
2
O
C for 2
-
3 hrs (nlt 1
hour), if there is no cracking or
breaking of coat, continue with
phosphate buffer, pH 6.8 at same
temperature for 1 hour or as per
monograph. If 1
-
2 fail, repeat for 12
different units
. 16 out of 18 indicate
test is affirmative.

Uses disintegration apparatus with
stimulated gastric fluid TS at 37+
-
2
O
C
for 1 hour, if there is no cracking or
breaking of coat, continue with
stimulated intestinal fluid at same
temperature for specified time

as per
monograph. If 1
-
2 fail, repeat for 12
different units. 16 out of 18 indicate
test is affirmative.

Modified release
tablets

Disintegration test
not ap
plicable

Disintegration test
not applicable

Disintegration tes
t
not applicable

Effervescent tablets

-
NA
-

A total of 6 units tested Uses 200ml of
water R at 15
-
25
O
C. Disintegrates
within 5 min. or as per monograph. If
1
-
2 fail, repeat for 12 different units.
16 out of 18 indicate test is affirmative.

-
NA
-

Soluble
tablets

-
NA
-

Uses disintegration apparatus Uses
liquid medium water R or specified
medium. Disintegrated within 3 min. If
1
-
2 fail, repeat for 12 different units.
16 out of 18 indicate test is affirmative.

-
NA
-

Dispersible tablets

-
NA
-

Uses disintegration

apparatus Uses
liquid medium water R or specified
medium. Disintegrated within 3 min. If
1
-
2 fail, repeat for 12 different units.
16 out of 18 indicate test is affirmative.

-
NA
-

Oral lyophilisates

-
NA
-

1 unit in a beaker of 200ml water R at
15
-
25
O
C.
Disintegrates within 3 min.
Repeated for total 6 units. Sample
accepted if all pass.

-
NA
-


Dissolution

Dissolution is the process by which a solid solute enters a solution. In the pharmaceutical industry, it may be defined as th
e
amount of drug substance that goes into solution per unit time under standardized conditions of liquid/solid interface,
temperatu
re and solvent composition. Dissolution is considered one of the most important quality control tests performed
on pharmaceutical dosage forms and is now developing into a tool for predicting bioavailability, and in some cases, replacing

clinical studies t
o determine bioequivalence. Dissolution behaviour of drugs has a significant effect on their pharmacological
activity. In fact, a direct relationship between
in vitro
dissolution rate of many drugs and their bioavailability has been
demonstrated and is gen
erally referred to as i
n vitro
-
in vivo
correlation, IVIVC
.

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Solid dosage forms may or may not disintegrate when they interact with gastrointestinal fluid following oral administr
ation
depending on their design
. For disintegrating solid oral dosage forms,
disintegration usually plays a vital role in the dissolution
process since it determines to a large extent the area of contact between the solid and liquid. However it is well known that

considerable dissolution of the drug can take place before complete d
isintegration of the dosage form, a phenomenon which
depends largely on the mechanism of disintegration and certain physicochemical properties of the drug, such as its solubility
.
This could be important when considering the motility of the drug or dosage
form, and the release of the drug at specific
sites, in the gastrointestinal tract. Thus, correlations have been established between disintegration times and dissolution
rates for various pharmaceutical tablets. It should be noted, however, that there is n
ot always an automatic correlation
between disintegration and dissolution, especially for drugs with very low dissolution rates.

For many drugs, particularly those that are poorly soluble in the gastric fluid, the rate
-
limiting step in the absorption proc
ess
is the dissolution rate and a dissolution rate determination can therefore be a useful guide to comparative bioavailability.
Since drug absorption and physiological availability depend on the availability of the drug substance in the dissolved state,

s
uitable dissolution characteristics are important property for a satisfactory tablet. The dissolution test measures the amoun
t
of time required for certain percentage of the drug substance in a tablet to go into solution under a specified set of
conditions
. It describes a step towards physiological availability of the drug substance, but it is not designed to measure the
safety or efficacy of the tablet being tested. It provides
in vitro
control procedure to eliminate variation among production
batches. The

dissolution medium must be aqueous and the pH of the medium should be controlled and should simulate
in
vivo
conditions. The dissolution medium should be 0.1M HCl and pH 6.8 buffer to simulate the biological extremes. The
possible role of bile salts in ab
sorption of highly insoluble drugs suggests the inclusion of physiological concentrations of
sodium taurocholate in the mildly acid or alkaline media. Studies have shown that low agitation must be used (i.e. in the
order of 50rpm) and that the tablet must
not be subjected to abrasion in keeping with the mild agitatio
n in the
gastrointestinal tract
.


Schematic diagram of the dissolution process

What i
s the definition of dissolution
?

Dissolution

is pharmaceutically defined as the rate of mass transfer from a solid surface into the dissolution medium or
solvent
under standardized conditions of liquid/solid interface, temperature and solvent composition. It is a dynamic
property that changes with time and explains the process by which a homogenous mixture of a solid or a liquid can be
obtained in a solvent. It hap
pens to chemically occur by the crystal break down into individual ions, atoms or molecules and
their transport into the solvent.

Why dissolution test
ing is used for pharmaceuticals
?

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Dissolution testing is a critical preformulation solubility analysis re
search tool in the process of drug discovery that entails
measuring the stability of the investigational product, achieving uniformity in production lots and determining its in vivo
availability. Thus this Dissolution testing is an essential requirement fo
r the development, establishment of in vitro
dissolution and in vivo performance (IVIVR), registration and quality control of different dosage forms.

What are the app
lications of dissolution tesing
?

Dissolution testing is widely used in the pharmaceutical

industry for optimization of formulation and quality control.

It is useful in the pharmaceutical and biotechnology industry to formulate drug dosage forms and to develop quality control
specifications for its manufacturing process.

To identify the critica
l manufacturing variable, like the binding agent effect, mixing effects, granulation procedure, coating
parameters and comparative profile studies.

To comply with guidelines set in the scale up and post approval changes (
SUPAC
) and
ICH
.

To select candidate formulation

To simulate food effect on bio availability.

To support waiver for bio equivalence requirements.

In th
e study of Bio waivers.

As a Surrogate for invivo studies.

In the In vitro invivo correlations.

Dissolution testing equipment

USP Rotating Basket Apparatus
:

The SS basket of 10 mesh is placed at a distance of 2.5 cm from the bottom of the vessel, is center
ed within 2 mm of the
centreline of the vessel. The shaft is rotated at 100 rpm and temperature of the medium is maintained at 37 C. Aliquots
should preferably be withdrawn midway between the surface of the medium and the bottom of the vessel and midway th
e
cylindrical edge of the basket and wall of the vessel.

Magnetic basket dissolution apparatus
:

The uniqueness of this device is that it enables reproducible and presice placement of the dosage form.It consists of a beake
r
(800 ml)and a magnetic basket of
50 mm long and 11 mm inner diameter whose exact placement is ensured by a magnetic
bar placed outside the beaker at the bottom.The additional modifications include the basket is constructed of epoxy resin
that inert is both acididc and basic environment. t
he agitation is provided by a three bladed, blades of 18 mm diameter set at
an angle of 60 angle and 45 0 from the vertical shaft of 7 mm, propeller with a diameter of 51 mm.The dissolution container,
of 600 ml of medium is inturn immersed in a water bath
so as to maintain the deisred 37 c. t propeller is immersed at a depth
of 41 mm of the beaker

For the adjustment of the pH electrodes are placed at a depth of 27 mm from the vertical top and 7 mm from the horizontal
beaker walls. With all these the device
can be used to characterize inter product variation of products.

Modified USP Basket apparatus
:

It is known fact that the flow of the medium should be sufficient for the dosage form such that the disintegrated particles
during the dissolution should be swe
pt by the medium from the basket screen. in order to fulfill this, the effort done was to
change the direction of the basket by the angle of 90 0 by bending the stirring rod so as to get L
-

shaped configuration. a
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cylindrical SS screen of 24
-
mesh was seam
welded and fitted over the teflon holder so as to hold the tablet firmly. This device
facilitates the increase in the dissolution rate because of the enhanced flow of the medium. wandering of the dosage form
within the basket is the major disadvantage whil
e the advantages include economically feasible and simple construction, dual
functionality i.e. both holding the dosage form as well as stirring of the holder.

Rotating Filter
-
Stationary Basket Apparatus
:

This device consists of stationary basket, a fluid
container and filter assembly with an external magnetic stirrer.

The

dissolution medium is contained in a fluid container of 1.5 l volume capacity.

There are a total of 4 ports: For sample, for glass
tube to favor the withdrawal of the aliquots, another fo
r replacement of the fresh medium and other for thermometer to
check the temperature.

The

basket is of 12 mesh which is kept stationary held at 2 to 5 cm from the bottom of the fluid
container.
The

dosage form is placed in the filter
providing different

i
ntensities of agitation.

USP Paddle method
:

It is also called USP apparatus
-
2, the paddle should be centered within 0.2 cm of the centerline of the vessel, 2.5 + 0.2 cm
from the bottom of the vessel. the shaft should rotate at a spped of 100 rpm with a te
mperature of about 37 0 C. the dosage
form should experience some movement under the paddle till disintegration progresses. once disintegration occurs, aliquots
should be drawn preferably from midway upper endge of the paddle and the surface of the medium
between the wall of the
vessel and stirrer shaft. the lowwer portion of vessel should be hemispherical and uniform in all aspects of weight, inside
diameter and curvature.in case of floating dosage forms statinless steel or glass helix is attached to the d
osage form. in this
case excess abrasion and wear of the doage forms due to the friction from the inner surfaces is observed, affecting the micro

environment adversely.

Forced Convection Sink Devices
:

An ideal dissolution process is one which will mimic
the invivo conditions by maintaining perfect sink conditions. these
perfect sink conditions can be maintained by either of the following systems:

a) Fixed fluid volume.

b) Multiple phase

c) Continuous fluid flow

a) Fixed fluid volume: in this system the fl
uid volume is kept fixed such that the volume is sufficient to maintain the drug
concentration below 10
-
20% of its solubility. fro example USP apparatus I and II.

b) Multiple phase: upon dissolution, the drug is either partitioned into water immiscible pha
se or adsoebed onto the solid
interface.

c) Continuous fluid flow: this system helps to know the solubility irrespective of its solubility or dosage strength. the dis
solved
drug along with the medium is removed constantly and is replaced by fresh medium.

Wurster
-
Polli Adsorption Method
:

in this method the dissolved drug is adsorbed by charcoal or bentonite. care should be taken regarding the adsorbent,
adsorbent should not alter the viscosity of the medium

Partition Method
:

In this device organic phase is
employed to remove the dissolved drug such that the drug would partition between the
lipophilic and hydrophillic phases. selection of organic phase plays a critical role.

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Dialysis Method
:

In this method dialysis membrane having minimal equilibrium time, a
dequate physical strength and solid particle retention is
employed

in this device dissolution medium is placed on one side of the membrane and the next side is dosage form and the
assembly is rotated at 15 rpm speed. aliquots are withdrawn at the distal end.
The advanced

method included baffled
rotating round bottomed fla
sk at 37 0C such that sloshing action is provided.

Rotating Flask apparatus
:

In this method a flask containing dissolution medium is rotated around its horizantal axis in a water bath kept at a
temperature of 37 C.The flask has a provision of sampling such

that aliquots can be withdrawn and the fresh medium can be
replaced back. This apparatus is best suited for oral solid dosage forms like tablets and capsules since they donot require
much agitation.

Flow Through Devices
:

For the drugs which saturate rapi
dly in large volumes of medium, USP apparatus will not serve the purpose. For this the
suitable device is flow through device. In this device unlimited quantity of fresh dissolution is available.

A dosage form is placed in a small cell and is subjected to

a stream of fresh dissolution media.

The various advantages include:

-

Changing of pH is simple and convenient.

-

number of parameters affceting are minimal.

-

Has method has built in filtration.

-

There is no problem of sample position.

-

Ideal hydrodyn
amic conditions for mild agitation, homogenicity and calculated solvent flow pattern are exercised.

-

Can be either open or closed type.


The basic design principle involved is that there is a vertical cylindrical cell of small dimensions having the capac
ity to taken
in a small volume. The dissolution medium is pumped with the help of pump from the bottom of the

cell top of cell.
T
here is
filtration device that prevents the movement of undissolved material and the obatined outflow fluid is clear solution t
hat can
be directly assayed. Temperature control, position of the dosage form and liquid agitation

can be controlled.

Continuous Flow Apparatus by Pernarowski et.al.
-

It consists of 10 mesh stainless steel basket stirrer assembly with an adjustable stirrer. the chamber is 3 necked flask of 3
3
mm and the rest two of 20 mm diameter. 1L of medium is employed within the flask.
T
he dissolution characteristics are
dependent u
pon the amount of medium pumped through the dissolution chamber.

Langenbucher Column
-
type flow through Method
:

This device is according to the dissolution basic design (as discussed above).The screen is constructed such that the medium
flows equally throug
h the entire cross section in a laminar pattern. This is again closed by a secondary screen, filter which
prevents the undissolved drug from being eluted.

Continuous Flow apparatus by Baun and walker
:

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Also called as constant
-

circulation apparatus. This co
nsists of a cell, holding dosage form, a reservior with dissolution
medium, a pump and water bath. there is a constant circulation apparatus that can be altered depending upon the dosage
form.

Continuous flow apparatus by Tingstad and Riegelman
:

A

cylind
rical glass cell of 6.1 cm long and 1.9 cm in diameter constructed with two glass filter funnels is used. The dissolution
cell has filter membranes which prevents the solid particles from being analyzed. There are also external valves to control t
he
excess

flow of solvent into the system. the air trap averts air bubbles. The complete assembly is immersed in a temperature
bath kept at 37 C.

Flow
-
Through Modified Column apparatus
:

The device consists of filter of 14 M
-
size made of nylon. the tubing from the
pump is connected to the dissolution cell. the
teflon faced stainlesssteel supports the screen resting on the bottom half of the filter holder. The direction of the flow is

such
that the particles donot fall through the screen. the rest of the process is t
he same.

Multichamber Continuous Flow Apparatus by Cakiryildiz et. al.
:

The word multi indicates that there are six chambers with 6 peristaltic pumps, a termperature bath with magnetic stirring
palte for 6 beakers, analyzer, With five identical dissolutio
n chambers and the rest one is for recirculation of a reference
solution.The dosage form is placed on the top of the bed of glass beads in the dissolution cell and later it is closed. then,

medium goes from reservoir to the bottom of the dissolution cell t
o its top then to analysis.

Continuous flow apparatus by Takenaka et.al.
:

The release of drug is measured with the aid of in vitro simulator device consisting of flow type dissolution container. The
dosage form is placed in the basket rotating at 94 rpm w
ith 300 ml of medium. then the medium is removed by collecting
reservior using peristaltic pump. aliquots are withdrawn using syringe and then filtered using Whatman filter paper and the
same volume is replaced immediately with fresh medium.