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DEPARTMENT OF PHARMACY
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Pharma-Technology
Assignment
Granulation Mechanisms:
Four key mechanisms or rate processes contribute to granulation
These include wetting and nucleation, coalescence or growth, consolidation, and attrition or
breakage. Initial wetting of the feed powder and existing granules by the binding fluid is strongly
influenced by spray rate or fluid distribution as well as feed formulation properties, in
comparison with mechanical mixing. Wetting promotes nucleation of fine powders, or coating in
the case of feed particle size in excess of drop size.
In the coalescence or growth stage, partially wetted primary particles and larger nuclei coalesce
to form granules composed of several particles. As granules grow, they are consolidated by
compaction forces due to bed agitation.
Formed granules may be particularly susceptible to attrition if they are inherently weak or if
flaws develop during drying.
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Spray drying:
Atomizer
Types and
Designs:
Centrifugal
Atomizers.
Kinetic
Energy Nozzles.
Pressur
e Nozzles.
Sonic Energy
Atomizers.
Granulation
techniques:
The three commonly used
granulation methods (categorized
based on the type of binder and the
process employed during
granulation) include:
wet
granulation
dry
granulation
Hot-melt granulation.
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The equipment that is used during the granulation processes is classified into the following three
major categories, based on the shearing strength it generates on the powder bed:
1. Low-shear granulators—twin shell (Peterson Kelly, PK) with an agitator bar, dough mixer
or planetary mixer, ribbon blenders, and fluid bed granulator without the rot granulator
2. Medium-shear granulators—fluid bed granulators with a rot granulator attachment
3. High-shear granulators.
2. Mixing of dry ingredients such as API, filler, and disintegrate, at high impeller and
chopper speeds for a short period of time (2–5 min).
3. Addition of a liquid binder (either binder solution or solvent) into the powder mixture,
while both the impeller and the chopper are running at a low speed.
4. Wet massing with both the impeller and the chopper running at a high speed.
5. Removal of the resulting wet granules from the granulator bowl, and drying them by
using an appropriate drying technique such as fluid-bed or tray drying.
6. Sieving the dried granules.
Dry granulation:
Briefly, in dry pharmaceutical granulation processing, the powder particles are
aggregated under high pressure, typically a pressure of 30–70 bar.
In the pharmaceutical industry, dry granulation processing favored a process called
slugging (where the powder is compressed into large tablets or slugs).The tablet slugs
were subsequently milled by a separate sizing machine to an appropriate particle size
distribution.
Hot-Melt Granulation
Hot-melt granulation utilizes a binder, which is a solid or semisolid at room temperature and
melts at a temperature below the melting point of API. Generally, the melting point of such
binders is between 30°C and 100°C. The binder, when heated near its melting point, liquefies or
becomes tacky. This tacky and liquefied form of binder agglomerates the powder mixture, which
upon cooling forms a solid granulated mass.
MECHANISM OF HIGH SHEAR WET GRANULATION
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mixing,
adding binder solution,
wetting and nucleation,
consolidation and growth,
And granule attrition and breakage.
HIGH-SHEAR GRANULATORS
Most of the high-shear granulators consist of a mixing bowl, a three-bladed impeller, and an
auxiliary chopper. The shape of the mixing bowl could be cylindrical or conical. The mixing
bowl can be jacketed for heating or cooling the contents in the bowl, by circulating hot or cool
liquid or steam through the jacket. An impeller is employed to mix the dry powder and spread
the granulating fluid. The impeller of the high-shear mixer granulator normally rotates at a speed
ranging from 100 to 500 rpm. The function of the chopper is to break down the wet mass to
produce granules. The rotation speed of the chopper ranges from 1000 to 3000 rpm.High-shear
granulator could be termed as either vertical or horizontal, based on the orientation and the
position of the impeller.
Top driven vertical granulators:
Bottom Driven:
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Spray Nozzle
A spray is a zone of liquid drops in a gas, and spraying is the act of breaking up a liquid into a
multitude of these droplets. The general purpose of spraying is to increase the surface area of a
given mass of liquid, in order to disperse it over the product area.
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Types of nozzles
1. Pressure nozzle: The fluid under pressure is broken up by its inherent instability and its
impact on the atmosphere, on another jet, or on a fixed plate.
2. Rotating nozzle (rotary atomizer): Fluid is fed at a low pressure to the center of a rapidly
rotating disk, and the centrifugal force breaks up the fluid. These types of nozzles are
used mainly in a spray drying application.
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3. Airless spray nozzle: The fluid is separated into two streams that are brought back
together at the nozzle orifice, where upon impingement, they form drops.
4. Gas atomizing nozzle (two-fluid nozzle): The two-fluid (binary) nozzle where the binder
solution (one fluid) is atomized by compressed air (second fluid) is the most commonly
used nozzle for fluid bed granulation
Extrusion:
1. Dry mixing:
Same mixer used for the granulation or in separate mixer.
2. Granulation:
Typically carried out in a batch type mixer/granulator including:
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planetary mixers,
vertical or horizontal high shear mixers,
sigma blade mixers.
3. EXTRUSION:
The third step is the extrusion step which forms the wet mass into rod-shaped particles.
The wet mass is forced through dies and shaped into small cylindrical particles having a
uniform diameter.
4. Spheronization
Carried out in a relatively simple piece of equipment. The working parts consist of a bowl
having fixed sidewalls with a rapidly rotating bottom plate or disk.
5. Drying
This can be accomplished in any dryer that can be used for conventional type granulations,
including tray dryers, column type fluid beds, and deck type vibratory fluid beds.
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References:
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