Extrusion/Spheronization as a Granulation Technique;

Definition:
Extrusion/spheronization is a multiple step process capable of making uniformly sized
spherical particles. The process is now being widely utilized in the pharmaceutical industry. It
is primarily used as a method to produce multiparticulates for immediate and controlled
release applications.
Diameter ranging from about 0.5mm to 10mm.

Principle:
The main objective of the extrusion spheronization is to produce pellets/spheroids of uniform size
with high drug loading capacity. Extrusion spheronization is a multiple process of wet mass
extrusion followed by spheronization to produce uniform size spherical particles, called as
spheroids, pellets, beads or matrix pellets depending upon the material as well as process used for
extrusion spheronization.

Process of extrusion and spheronization

Extrusion spheronization follows mainly five steps that is mixing or blending, extrusion,
spheronization, coating and finally drying, which can be explained/described as:

 Dry mixing of ingredient to achieve homogenous powder dispersion.

 Wet massing to produce a sufficient plastic mass.
 Extrusion to form rod shaped particles of uniform diameter.
 Spheronization to round off these rod shaped particles into spherical particles with narrow
size distribution.
 Drying to achieve desired final moisture content.
 Screening to obtain desired size of spheres/pellets.

Steps and Equipments used in Extrusion/Spheronization:

Wet
Dry Mixing Extrusion
Granulation

Spheronization Drying

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 1. Dry Mixing:
 During the 1st step, powder is dry mixed to achieve a uniform dispersion before wet
granulation.
 It is generally carried out the same mixer used for granulation.
 The uniformity of the dry mix has a significant effect on the quality of granulation or
in turn the spherical particle produced.
 An uneven distribution of the material has wide difference in properties in properties
such ad size and solubility result in localized over wetting.
 The more soluble and finally divided components can also dissolve and become the
part of granulating fluid.
 The fluid rich in soluble compounds, can either remain as over wetted regions or, with
continued wet massing, can be redistributed.
 Sphere uniformity is very much dependant on the uniform distribution and
composition of the granulating fluid.
2. Granulation:
 Granulation involves preparation of the plastic mass of the material.
 Different types of granulators are used to perform the mixing of the powder blend
and the granulation liquid.
 The most commonly used granulators are a planetary mixer, high shear or sigma
blade mixer.
 Gao et al. have proposed a protocol that could be a valuable asset in a formulation
development project to assess the physical properties of wet masses and to predict
formation and pellet quality.
 So, the tedious and expensive pre-production (preformulation and optimization)
work could be considerably reduced.
 The wet granulation process plays an important role in extrusion–spheronization.
 With the introduction of a twin-screw extruder (TSE), it allows the possibility of
wet granulation to run continuously in contrast to a conventional batch process
using a high shear mixer (HSM).
3. Extrusion:
 Prepared plastic mass undergoes extrusion in which pressure is applied to a mass
until it flows out through an orifice to produce the extrudates.
 The extrudate length may vary, depending on the physical characteristics of the
materials to be extruded, method of extrusion, and how particles are manipulated
after extrusion.
 Extrusion is performed using four main classes of extruders: screw, sieve and
basket, roll, and ram extruders.

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Different types of Extruders used in extrusion-spheronization:
Type of Extruder Mechanism
Screw Extruder Utilizes a screw to develop the necessary
pressure to force the material to flow
through uniform openings
Sieve Extruder A rotating or oscillating arm presses the
damp material through a sieve
Basket Extruder Similar to sieve extruders, except that the
sieve or screen is part of a vertical
cylindrical wall.
Roll Extruder Roll extruders operate by feeding material
between a roller and a perforated plate or
ring die.
Ram Extruder A piston riding inside a cylinder or channel
is used to compress material and force it
through an orifice on the forward stroke.

Screw Extruder (Axial Type)

Screw Extruder (Radial Type)

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 (A)Sieve Extruder (B) Basket Extruder

Ram Extruder
4. Spheronization:
 In spheronization, the extruded, cylindrically shaped particles are broken into
uniform lengths and are gradually transformed into spherical shapes; this
shaping process is due to plastic deformation. As extrudates are first broken
into nearly uniform lengths, all three dimensions of agglomerate shape are
determined, and spheres with a nearly uniform diameter are produced.

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  In the spheronization process, different stages can be distinguished depending
on the shape of the particles, i.e., starting from a cylinder over a cylinder with
rounded edges, dumbbells, and elliptical particles to eventually perfect spheres
 pellet-forming mechanism might exist.
 In this mechanism, a twisting of the cylinder occurs after the formation of
cylinders with rounded edges, finally resulting in the breaking of the cylinder
into two distinct parts. Both parts have a round and a flat side.
 Due to the rotational and the frictional forces involved in the spheronization
process, the edges of the flat side fold together like a flower forming the cavity
observed in certain pellets.
 A spheronizer is a device consisting of a vertical hallow cylinder with a
horizontal rotating disk (friction plate) located inside.
 Extrudates are charged onto the rotating plate and broken into short segments
by contact with friction plate, collisions between particles and collisions with
the wall.
 Mechanical energy introduced by the spinning friction plate is transmitted into
kinetic energy in the form of mechanically fluidized bed. Further processing
will cause the extrudate to deform gradually into a spherical shape.
 The friction plate has a grooved surface to increase the frictional forces. Two
types of the geometry of the grooves exist, crosshatch geometry where the
grooves form right angles and radial geometry where a radial pattern is used.

Spheronizer
5. Drying:
 The fourth and final step of the process is the drying of the pellets. The
pellets can be dried at room temperature or at elevated temperature in a
fluidized bed or in an oven.

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Advantages:
The pellets or beads produced by the extrusion spheronization offer the following advantages:
 It Produces spheroids with high loading capacity of active ingredient
without producing extensively large particles.
 It produces particles of uniform size with narrow size distribution and
good flow properties.
 Successful coating is applied to spheroid because of its spherical shape and
low surface area to volume ratio.
 Pellets composed of different drugs can be blended and formulated in
single unit dosage form that facilitates delivery of two or more chemically
compatible or incompatible drug at the same or different site in GI tract.
 Pellets are frequently used in controlled release delivery system as it
facilitates free dispersion of spheroids in the GI tract and offer flexibility
for further modification.
 It improves the safety and efficiency of active ingredient.
 It helps to increase bioavailability of drugs by controlling or modifying the
release rate of drugs.

Disadvantages:
 Requires high energy input in extrusion.
 Lower melting point risks situations where melting and softening of the binder
occurs during handling and storage of agglomerates.

Applications:
 Extrusion Spheronization has been used in agrochemicals, detergent additives,
sweeteners, food and now it is used in pharmaceuticals.
 Extrusion spheronization is primarily used for the production of
multiarticulate for oral controlled drug delivery system.
 It is more labour intensive than other granulation method, but it is useful when
uniform spherical shape, uniform size, good flow properties, reproducibility in
packing, high strength, low friability and smooth surface of granules is
desired.
 Extrusion spheronization process has gained worldwide attention because it is
a simple and fast processing technology.
 Any pharmaceutical products utilize pellets or beads as a drug delivery system
can be effectively produced by the extrusion spheronization process.
 Wet mass extrusion and spheronization is established method for the
production of spherical pellets, and are coated effectively to achieve controlled
release product.

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References:
 https://www.slideshare.net/CalevaProcessSolutions/extrusion-spheronization
 http://www.sphinxsai.com/Oct_dec_2010_vol2_no.4/PharmTech_vol2_no.4_1_pdf/
PT=44%20(2429-2433).pdf
 http://www.authorstream.com/Presentation/ravikiranowku-1962089-extrusion-
spheronization/
 http://www.authorstream.com/Presentation/ravikiranowku-1962089-extrusion-
spheronization/

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