Powder granulation is a procedure of size expansion ( Litster & A ; Ennis, 2004 ) ( Swarbrick & A ; Boylan, 2006 ) that incorporate the little atoms to agglomerate together to do a larger atoms in a manner that the chief constituents can still be detected ( Ennis, 2005 ) .
By and large, each tablet contains different types of ingredient but the active ingredients are more of import one. During the combination of all constituents, it should be guaranteed that active ingredients are distributed every bit in different part. While sometimes during the blending or compaction, the ingredients separate from each other ; harmonizing to their difference in atom size, denseness, squeezability and flow features. So to accomplish a regular consequence the pulverizations must flux invariably therefore atoms should be granulated ( D.Tousey, 2002 )
The definition of granulation granulation contain
particle-size distribution and denseness to achieve proper flow and
achieve volume of fill ( i.e. , tablet weight ) . In other words, the
pulverizations must flux systematically to achieve consistent consequences.
The main grounds to grain pulverizations for the
industry of pharmaceutical dose signifiers are
described by Kristensen and Schaefer. [ 1 ]
. To better pulverization flow belongingss for dose filling
and compaction procedures.
. To extinguish wet granulation induced degradants and
to better merchandise stableness.
. To forestall active merchandise ingredient from segregating.
. To cut down majority volume thereby minimising storage
and heightening conveyance.
. To cut down possible environmental and safety jeopardy ( 16,2806 )
Wet granulation is a subset of size expansion ( 1-5 ) , which involves any procedure
whereby little atoms are agglomerated, compacted, or otherwise brought together
into larger, comparatively lasting constructions in which the original atoms can still be
Distinguished. Granulation engineering and size-enlargement procedures have been
used by a broad scope of industries, from the pharmaceutical industry to fertilizer
or detergent production to the mineral processing industries. Size enlargement by and large
encompasses a assortment of unit operations or treating techniques dedicated to
atom agglomeration. These procedures can be slackly broken down into agitation
and compaction methods. ( 10,31 )
Powder granulation is a procedure of pulverization size
expansion that incorporates little atoms into larger
1s. The definition of granulation comprises a scope of
different size expansion methods that can be classified
as either dry or wet. In wet methods, a suited liquid is
used to agglomerate the little pulverization atoms into a
mass. The wet mass is later dried and sized for
farther down-stream processing demands. Wet granulation
methods have been the most widely used pulverization
granulation engineering in the production of pharmaceutical
merchandises, peculiarly in modern pharmaceutical
Traditionally, tablets have been made by granulation, a
procedure that imparts two primary necessities to preparations:
compactibility and fluidness. Both wet granulation
and dry granulation ( sloging or turn over compression ) are used
( Table 1 ) . Regardless of whether tablets are made by direct
compaction or granulation, the first stairss, milling and
commixture, are the same ; the subsequent stairss differ.
The wet massing of pulverizations is typically carried out in
high-shear sociables prior to wet showing. The moisture
granules are frequently dried in fluidized-bed equipment,
heightening the efficiency of the procedure. Alternatively, moisture
granulation may be carried out in fluid-bed driergranulators
in which the liquid stage is sprayed onto
fluidized pulverizations while the hot air flow dries the granules.
This procedure reduces the figure of managing stairss and the
clip and infinite needed for granulation ; it can be
automated ( 16,3165 )
-Nonhomogeneous distribution of binder and drug
substance gives drug-rich or drug-poor mulcts
-Decomposition of drug substance due to residual
-Uneven granule size ( excessively many or to few mulcts ) leads
to compression or uniformity jobs
Naturally tablets merely possess these advantages if they
are decently formulated and manufactured. A wellprepared
tablet should possess the undermentioned qualities:
1. It should, within permitted bounds, contain the declared
dosage of drug.
2. It should be sufficiently strong to defy the emphasiss
of industry, conveyance, and managing so as to make
the patient intact.
3. It should present its dosage of drug at the site and at the
4. Its size, gustatory sensation, and visual aspect should non take away from
its acceptableness by the patient. ( 16,3174 )
The procedure of granulation is basically
one of size expansion, and it serves several intents in
the tablet fabrication procedure:
1. It improves flow by increasing atom size, since big
atoms flow more readily than little 1s.
2. It improves compaction features, adding to the
cohesive strength of the tablet.
3. Once a homogenous mixture has been achieved,
segregation is prevented, since atoms that are stuck
together can non divide.
4. It reduces dust.
Both wet and dry granulation techniques are available
The first phase in the wet granulation procedure is frequently a dry
blending phase in which the active constituent is assorted with
a dilutant. Many drugs need to be administered in doses of
merely a few mg or even less, yet a tablet that weighs
less than approximately 50 milligram is hard for the patient to manage
handily. It is hence necessary to increase the majority
of such a tablet with a dilutant. Some normally used
dilutants are listed in Table 1.
The ideal dilutant would be both chemically and
physiologically inert, and would non interfere with the
bioavailability of the active ingredient. It should besides be
cheap and be easy tabletted since, if the proportion
of active ingredient is little, the overall tabletting
belongingss of the mixture are mostly governed by those
of the dilutant.
Lactose is by far the most often used dilutant for
solid dose signifiers. An cheap disaccharide obtained
as a byproduct of the cheese industry. Probably the 2nd most normally used dilutant in the
wet granulation procedure is dibasic Ca phosphate. This
substance is virtually indissoluble in H2O and hence is
ever used in concurrence with a disintegrating agent
The intent of the commixture phase is to guarantee that the
pulverization blend and therefore the resulting tablets are
homogenous in content. A random mixture is defined as
one where the chance of trying a given type of
atom is relative to the figure of such atoms in
the entire mixture. Therefore, the purpose is to bring forth a mixture
such that when a sample is removed, the relation
proportions of the constituents of that sample are the
same as in the mixture as a whole. Although in general a size difference between
constituents can take to segregation, a state of affairs where
there is a big difference in sizes between constituents
may be good. In such fortunes, little atoms
of one constituent can go trapped in abnormalities in
the surface of the larger constituent. These are non random
mixtures, as the atoms of the two constituents can non
act independently. This construct is called “ ordered
blending ” and it has found pertinence in the industry
of solid dose signifiers incorporating little measures of extremely
potent active ingredients ( 5 ) ( see the article on Blenders
and Blending in this encyclopaedia ) .
The implicit in procedure of size expansion in moisture
granulation is achieved by either one or both of two
different mechanisms. First, next solid atoms may
be stuck together utilizing an adhesive. Such substances are
known as binders or graining agents. Second,
disintegration of the solid in the granulating liquid can
occur, followed by vaporization of the liquid stage of the
latter. This will ensue in the deposition of dissolved
stuff on atom surfaces, organizing alleged crystal
Bridgess. The happening of this mechanism will depend on
the solubility of the solids in the liquid stage.
The traditional piece of graining setup is the
shear granulator. Its map is to homogeneously
integrate an adhesive and syrupy liquid such as amylum
paste into a mass of dry pulverization to organize agglomerates. It
follows that a considerable shearing force demands to be
exerted. The assorted solids are loaded into the bowl of the
sociable, and the liquid added with agitation. The moistness solid
is so forced through a comparatively harsh screen ( about
1-2 millimeter ) , frequently by agencies of hovering bars, to give distinct granules.
the wet granulation procedure is a
long and therefore expensive process, which has been
improved by the debut of high-velocity sociable
granulators. These have fomenter and chopping blades,
which enable commixture, wet massing, and granulation to take
topographic point in the same piece of setup. In such devices, the
granulation procedure takes topographic point highly quickly.
A farther technique is fluid-bed granulation. Air is
passed into the pulverization bed from below. This causes the
atom, of pulverization to organize a suspension in the air and
gives effectual commixture. The granulating fluid is so
sprayed over the atoms, which adhere on hit and
they are so dried in the het air watercourse.
The wet granulation procedure, setup, and pharmaceutical
applications have been comprehensively reviewed
by Kristensen and Schaefer ( 8 ) ( see the article on Tablet
Granulation in this encyclopaedia ) .
After the procedure of granulation, the merchandise exists as a moisture
mass from which the liquid must be removed, since the
presence of H2O leads to the damage of flow belongingss,
and possibly to chemical instability
The fluidized bed desiccant is the most normally used
device for drying tablet granules. The solid is fluidized
from below by a jet of hot air, and so each granule
becomes separated from its neighbours. The air provides an
effectual agencies of heat transportation, every bit good as of taking
H2O vapour. The velocity of the drying procedure is governed
by the distance that H2O molecules must spread before
they arrive at the evaporative surface. Since the moisture
granules are present as single units, the upper limit
distance over which diffusion occurs is equal to the radius
of a granule. Hence, fluidized bed drying is a rapid procedure. The temperature of the bed can be exactly controlled, and a free-flowing merchandise consequences.
Second commixture phase
When the drying procedure is complete, it is likely that the
merchandise will hold cohered into comparatively big multitudes,
particularly if tray drying has been used. The dried stuff
is hence passed through a screen ( normally 250-700 millimeter )
to interrupt up sums and to give a comparatively uniformly
sized granule. A 2nd commixture phase now follows in which
several of import ingredients of the preparation are added
When the tablet preparation is compressed, the sides of the
tablet are brought into confidant contact with the dice wall.
The tablet must so be ejected from the dice, affecting the
motion of the side of the tablet relation to the dice wall.
Therefore, clash between the tablet and the dice wall
must be overcome. With stuffs such as lactose, clash
opposition can be considerable, and it may be impossible to
take the tablet from the dice without harm to the tablet
or to the tablet imperativeness. Therefore, a lubricator is about
constantly included in a tablet preparation. A lubricator is a
substance that deforms easy when sheared between two
surfaces, and therefore when interposed between the tablet
and the dice wall, provides a readily deformable movie (
The commixture procedure is
highly of import here, and blending clip, sociable type,
and batch size ( 16 ) have all been shown to act upon
tablet belongingss. Therefore, there is a demand to set up a
minimal lubricant concentration and an optimum
commixture clip within which equal lubrication is
achieved without the development of unwanted tablet
features. To guarantee batch-to-batch uniformity, the
parametric quantities of the blending procedure such as type of sociable,
batch size, and mixing clip must be kept as changeless
as possible. A mixing clip of 2-5 min normally suffices
to give equal lubrication