Scale-Up of Extrusion and Spheronization

8/10/2019 Scale-Up of Extrusion and Spheronization

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Introduction

Pelletizationas the process of transforming a wet,solid mass of finely divided particles into dry, sphericalbodies by a continuous rolling or tumbling motion.

Extrusion-spheronizationis a pelletization process for

making pellets that are amenable for immediate andcontrolled-release preparations.

It includes the processes of blending, granulation,extrusion, spheronization, drying,

screening, functional coating (if needed), andencapsulation or compression into tablets.


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Extrusion-

spheronizationProcess And

Associated Unit

Operations


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Conti

Variables For Successful Development Of The Extrusion-spheronizationProcess Are:

Formulation (selection of excipients)

Wet granulation (particularly moisture content)

Extruder design and extrusion parameters

Spheronizer design and spheronization parameters


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Dimensional Analysis in Scale-Up ofExtrusion

Express similarities between two scales, both geometric anddynamic.

The ratio of screw diameter is the basis for scaling.

The ratio of the large diameter D2 of the large scale unit to the smalldiameter D1 of the lab unit is represented by the lower case d.


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Dimensional Analysis in Scale-Up ofExtrusion

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 asa power of the screw diameter ratio, d.


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The cube rule for mixing states that at constant screw speed, outputand power consumption increase with d3when 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.


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The secondary variablessuch as

shear rate

mean residence time

power consumptionthroughput rate

All are expressed as a function of theprimary variables.


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Shear RateThe 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, theshear rate is constant as 1+v-h = 0.

At varying screw speeds across scale, the total shear Sremains constant.


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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 thematerial distribution (homogeneity) in the extruder is independent ofscrew speed.


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Power Consumption

The torque of extrusion (F) is the energy expended by the motordrive in rotating the screw(s) and is expressed as

F = E/N

where E is the power consumption to drive the screw shaft at aspeed of N rpm


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Specific Energy Consumption

the specific energy consumption, K which is the power normalizedfor throughput Q and expressed as

K = E/Q

K =(FN)/Q


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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 variablethat 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.


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Number of revolutions (N)

N = ST

Peripheral velocity (V)

V = DS Rotational travel (X)

X = DST


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For a spheronizing particle, the kinetic parameter is the centrifugal forceand is determined by plate speed and diameter while g represents thegravitational field.

The Froude numberis 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).


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

as given by

With M being the material load.


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References Raman M. Iyer, Pharmaceutical Process Scale-Up, Marcel Dekker series:

Scale-Up of Extrusion and Spheronization: Page No. 325371

Beatrice Nkem Chukwumezie,Feasibility Studies in Spheronization andScale-up of Ibuprofen Microparticulates Using the Rotor Disk Fluid-BedTechnology,AAPS PharmSciTech 2002; 3 (1) article 2

(http://www.aapspharmscitech.org )

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Scale-Up of Extrusion and Spheronization