Scale-Up of Extrusion and

Spheronization

Introduction
Pelletization as the process of transforming a wet,
solid mass of finely divided particles into dry, spherical
bodies by a continuous rolling or tumbling motion.
Extrusion-spheronization is a pelletization process for
making pellets that are amenable for immediate and
controlled-release preparations.
It includes the processes of blending, granulation,
extrusion, spheronization, drying,
screening, functional coating (if needed), and
encapsulation or compression into tablets.

Extrusionspheronization
Process And
Associated Unit
Operations

Conti
Variables For Successful Development Of The Extrusion-spheronization
Process Are:
Formulation (selection of excipients)
Wet granulation (particularly moisture content)
Extruder design and extrusion parameters
Spheronizer design and spheronization parameters

Dimensional Analysis in Scale-Up of

Extrusion
Express similarities between two scales, both geometric and
dynamic.
The ratio of screw diameter is the basis for scaling.
The ratio of the large diameter D2 of the large scale unit to the small
diameter D1 of the lab unit is represented by the lower case d.

Dimensional Analysis in Scale-Up of

Extrusion
The primary scaling variables are
Channel depth H
Screw length L
Helix angle f
Screw speed N
The ratio of the primary variables of the two scales is then expressed as
a power of the screw diameter ratio, d.

 The cube rule for mixing states that at constant screw speed, output
and power consumption increase with d3 when H/D ratio is constant.
The square-root rule for conveying of material states that when
channel depth is increased and screw speed decreased with
The output rate increases with d2, while power consumption increases
by d2.5.

Conti..
The secondary variables such as
shear rate
mean residence time
power consumption
throughput rate
All are expressed as a function of the primary variables.

Shear Rate

The shear rate (or material displacement rate) in the

screw channel is a function of the primary variables D,
N, and H and proportional to 1+v-h, a scale-up factor.
For a given type of screw with fixed helix angle (b = 0),
at fixed speed, N and fixed L/D and H/D ratios, the
shear rate is constant as 1+v-h = 0.
At varying screw speeds across scale, the total shear S
remains constant.

Total Shear S
A constant total shear S suggests that the profiles of the material in
the two different size screw extruders are identical or that the
material distribution (homogeneity) in the extruder is independent of
screw speed.

Power Consumption
The torque of extrusion (F) is the energy expended by the motor
drive in rotating the screw(s) and is expressed as
F = E/N
where E is the power consumption to drive the screw shaft at a
speed of N rpm

Specific Energy Consumption

the specific energy consumption, K which is the power normalized
for throughput Q and expressed as
K = E/Q
K =(FN)/Q

Scale up Of Spheronization
Critical process variables are plate speed and
residence time of pellets in the spheronizer
while the plate diameter is a geometrical variable
that increases with material load.
For a given Plate speed (S rpm),
Plate diameter (D)
Spheronizing time (T)
The scale-up may be based on keeping constant
Number of revolutions,
Rotational distance
Peripheral velocity.

 Number of revolutions (N)

N = ST
Peripheral velocity (V)
V = DS
Rotational travel (X)
X = DST

 For a spheronizing particle, the kinetic parameter is the centrifugal force

and is determined by plate speed and diameter while g represents the
gravitational field.
The Froude number is expressed as

U is the characteristic velocity, the peripheral velocity (m/s),

g is the acceleration due to gravity (m/s2),
L is the characteristic length, the plate diameter (m).

 Since g is a constant, the scale-up factor becomes the centrifugal force

as given by

With M being the material load.

References
Raman M. Iyer, Pharmaceutical Process Scale-Up, Marcel Dekker series:
Scale-Up of Extrusion and Spheronization: Page No. 325 371
Beatrice Nkem Chukwumezie, Feasibility Studies in Spheronization and
Scale-up of Ibuprofen Microparticulates Using the Rotor Disk Fluid-Bed
Technology, AAPS PharmSciTech 2002; 3 (1) article 2
(http://www.aapspharmscitech.org)