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Wet Granulation

Granulation is the process of agglomerating particles into larger aggregates using a liquid binder in a tumbling drum or fluidized bed. This binds particles through capillary pressure, surface tension, and viscous forces. Wet granulation improves properties like flow, uniformity, density, and dissolution which enhances tablet production. The granulation process and parameters like binder type and amount, equipment used, and granule properties can be controlled. Fluid bed granulators allow for simultaneous drying but require more energy while mixer granulators can handle difficult powders but require transfer for drying. Granule growth occurs through wetting, consolidation, and breakage, influenced by liquid and particle properties. There are two classes of growth - steady or

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221 views3 pages

Wet Granulation

Granulation is the process of agglomerating particles into larger aggregates using a liquid binder in a tumbling drum or fluidized bed. This binds particles through capillary pressure, surface tension, and viscous forces. Wet granulation improves properties like flow, uniformity, density, and dissolution which enhances tablet production. The granulation process and parameters like binder type and amount, equipment used, and granule properties can be controlled. Fluid bed granulators allow for simultaneous drying but require more energy while mixer granulators can handle difficult powders but require transfer for drying. Granule growth occurs through wetting, consolidation, and breakage, influenced by liquid and particle properties. There are two classes of growth - steady or

Uploaded by

uddhav
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Granulation is the process of agglomerating particles together into larger,

semipermanent aggregates by spraying a liquid binder onto the particles as they


are agitated in a tumbling drum, fluidized bed, high shear mixer, or similar device.
The liquid binds the particles together by a combination of capillary pressure,
surface tension, and viscous forces until more permanent bonds are formed by
subsequent drying or sintering.
Why Granulate?
Improved flow and handling
Increased uniformity in finished product (less ingredient segregation)
Increased density
-reduced volume required for processing and storage
-decreased batch size
Reductions in dust
Can improve dissolution (surfactant effects)
Improved compression characteristics of the drug
Improve the appearance of the tablet
Controlled drug release rate
Wet Granulation Parameters Formulation:
Formulation:
Primary particle size and size distribution
Ingredient composition
Binder type, wetting properties, and amount Process:
Process:
Binder method of addition
Equipment parameters (depends on type of operation) Product:
Product:
Granule size, size distribution, shape, bulk and tapped density
Fluid Bed Granulators
Advantages
High volumetric intensity
Simultaneous granulation and drying
Control of granule morphology
Porous agglomerates from fine powders (0.2-1mm)
High strength layered granules (0.5-3mm)
Good heat transfer
Good scale up
Disadvantages
Quenching
Operating cost (air handling)
Attrition, dust recovery
Residence time distribution (well mixed)
Cant handle very fine powders
Mixer Granulators

Advantages
Can handle cohesive powders
Can handle small particle size of ingredients
Can handle viscous and foaming binders
Produces small, dense granules
Disadvantages
Expensive equipment
Requires transfer to another unit for drying
Produces ONLY dense granules
Produces non-spherical granules
Difficult to scale up
Wet Granulation Rate Process
Wetting and Nucleation -> Consolidation and Growth -> Breakage and Attrition
All of these happen simultaneously. So its hard to control.
The degree of wetting pays an important role in:
the compression characteristics of the granules
the drug release rate from finished tablets
The ability of a liquid to wet a solid is described in terms of the contact angle ()
If = 0, Perfect wetting; 0< <90 Partial; 90< <180 Non wetting; =180
Complete non wetting

f viscosity) is too high, the penetration time will take too long.
Macro voids halt the liquids from penetrating the powder beds.
Spray flux should be low. That helps to keep minimal drop overlap.
Drop controlled nucleation occurs when 1 drop = 1 nucleus. This is the ideal
operating regime
The height from which the liquid falls also affects the wetting mechanism.
Any general model of granule growth behavior must consider the
following factors:

Particle-binder mixtures below a minimum strength do not granulate and


only form a weak crumb material.
Coalescence growth is promoted by increased liquid content.
Granule properties vary with time. Consolidation can cause a system to
change from deformable and surface-dry, to elastic and surface-wet.
There are two broad classes of granule growth behavior, steady growth
and induction behavior, depending on the deformability and consolidation
rate of the particle-binder matrix.

There are two broad classes of growth behavior which can occur-either
steady growth or induction time behavior. Which type of growth occurs
depends on the deformability and rate of consolidation of the granules.

Weak, deformable granules form a large area of contact during collision and
liquid binder may be squeezed into this contact zone.
If this bond is strong enough to resist the separating forces within the
granulator, then the pair of granules will be rounded into a new larger
granule. This behavior leads to a steady increase in granule size (steady
growth) and is common in systems with coarse, narrowly-sized particles and
low surface tension and/or low viscosity binder liquids.
Strong, nondeformable, slowly-consolidating granules do not deform
sufficiently during impact to form a strong contact bond. Pairs of collided
granules quickly break apart, and there is a period of little or no granule
growth-the "induction" period (also called the "nuclei" region or
"consolidation" period). The length of this induction period decreases with
increasing liquid content. If granules consolidate sufficiently, then liquid
binder may eventually be squeezed to their surface. This surface liquid
enables strong bonds to form between granules without the need for large
amounts of deformation. This triggers rapid granule growth until the granules
become so large that the torque exerted on granule dumbbells prevents
further coalescence.
This class of behavior is frequent in systems with fine particles and/or
viscous binders.

Increasing process agitation intensity will increase the typical impact


velocity and, hence, increase the deformation number. Increasing process
agitation intensity will increase the extent of granule consolidation and,
hence, increase the maximum pore saturation.
Increasing liquid viscosity or decreasing particle size both increase
granule dynamic yield stress, but have variable effects on minimum
porosity.
Decreasing binder surface tension has been found to decrease both
dynamic yield stress and the extent of granule consolidation.

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