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1. Pelletization
Ravish Yadav

2. CONTENTS
 Definition
 Classification
 Advantages & uses
 Mechanism of pellet formation & growth
 Pelletization equipments
o Coating pans
o Fluid bed equipments
o Centrifuge equipment
2

3. DEFINATION OF PELLETIZATION
• Pelletization is an agglomeration process that converts fine powders
or granules of bulk drug and excipients into small, free flowing,
spherical or semi-spherical units, referred to as pellets.
• Pellets range in size, typically between 0.5-1.5mm
3

4. Pelletization
Agitation compaction layering globulation
Balling compression powder spray
drying
extrusion/ solution / spray
spheronization suspension congealing
4

5. ADVANTAGES
• Pellets disperse freely in the gastrointestinal tract, they
invariably maximize drug absorption, reduce peak plasma
fluctuation and minimize potential side effects without
appreciably lowering drug bioavailability
• Pellets also reduce variation in gastric emptying rate and overall
transit time
• Intra and inter subject variability of plasma prophile which are
common with single unit regimen are minimized
• High oral concentration of bio-active agent which are
inherently be irritative or anesthetic can be avoided.
• pellets are less susceptible to dose dumping than the reservoir
type single unit formulation
5

6. USES
• To deliver the bioactive agents at a specific sites within the
gastrointestinal tract
• Sustain the action of drug over an extended period of time
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7. MECHANISM OF PELLET FORMATION
A] Bonding mechanism
1] Attraction between solid particles
 Attractive forces are short range forces that causes
solid particle adhere together only if they are
brought close enough together
 These forces diminishes as the size of particle or
inter-particle distance increases
 Attractive forces may be molecular ( valence & van
der waals ), electrostatic or magnetic in nature
7

8. 2 ] interfacial forces and capillary pressure in movable liquid
surface
 In wet agglomeration the liquid phase in system initially
generate the cohesive forces between the particles
 When liquid is added part of void space in randomly packed
material is filled with liquid to form discrete lens like ring
forming agglomerate, this known as pendular state
 Capillary state is reached when all void space within the
agglomerate is completely filled with liquid
 In between pendular and capillary state there exist a
funicular state in which liquid bridge containing gas & pores
filled with liquid are present
 In droplet state liquid completely envelopes the
agglomerate. The primary particles are held together by
surface tension of droplet.
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9. 9

10. 3 ] Adhesional & cohesional forces in bonding
bridges that are not freely movable
 viscous binder & thin adsorption layer provide bonds that are based
on immobile liquid bridges.
Highly viscous binder adhere to surface of solid particle to generate
strong bond.
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11. 4 ] solid bridges
It largely determines the strength of final cured or dried product.
Different mechanisms are as below
a) Crystallization of dissolved substances
b) Hardening binders
c) Kelting
d) Sintering & chemical reaction
 This indicates that solid bridges formed at high pressure &
temperature.
11

12. 5 ] Mechanical interlocking
It may occurs during agitation & compression
of fibrous, flat shaped and bulky particles
It is minor contributor to pellet strength
12

13. ELEMETARY GROWTH MECHANISMS
A. Nucleation :-in this primary particles are drawn together
to form three phase air-water-solid nuclei. The particles
are held together by liquid bridges.
B. Coalescence :- the formation of large size particles
following random collision of well formed nuclei
C. Layering :- it is an successive addition of material on
already formed nuclei. Material added may be dry or
moister
D. Abrasion transfer :- it involves the transfer of material
from one particle to another without any preference in
either direction
E. Size reduction :- well formed particle may undergo size
reduction due to attrition, breakage and shatter
13

14. PELLET FORMATION & GROWTH
1 ] balling
This mechanism occurs mainly in rotating drum, Pan
or disc
a) nucleation
b) Transition
c) ball growth
14

15. 2 ] drug layering
Pelletization by layering involves the deposition of
successive layers of drug entities from solution,
suspension or dry powder on preformed nuclei which
may be crystals, granules or starter seeds.
Solution / suspension layering
Powder layering
15

16. 3 ] compaction
It is a form of pressure agglomeration in which drug particles or
granules are formed together with or without formulation aids by a
mechanical forces to generate pellets of well defined shape or size.
It can be subdivided into compression & extrusion.
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17. 4 ] globulation
It is a process where hot melts, solutions or suspensions are atomized
to generate spherical particles or pellets.
In globulation, atomization produces solid particles directly from the
liquid phase through evaporation or cooling & subsequent solidification
of hot melts , solutions or suspensions.
This occurs by spray drying & spray congeling.
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18. PELLETIZATION EQUIPMENTS
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19. COATING PANS
1 ] CONVENTIONAL COATING PANS
Advantages
Less expensive
Versatile in that both drug layering & pellet coating are possible
Disadvantages
Higher labor cost, longer processing time & lower yields
Lack of process control
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20. Rotating pans
Pear, hexagonal, angular,
spherical, elliptical & do-nut
shaped pans are available with
size ranging from 6-90 inches in
diameter
Pellet movement is best
described as cascading with
maximum turbulence in the
center of load. Dead spots can
form at the back & front of the
pan & it is not uncommon to
see large particle riding along
the perimeter of the pan.
20

21. Air supply system
Equipped with both drying & exhaust air lines.
Hot air is used to facilitate solvent evaporation, to dry the
pellets between spray interval.
Supply air duct should be positioned close to the bottom of
cascading bed.
The exhaust dust should be situated in upper third of pan.
Exhaust flow rate should be maintained at a fixed level such as
450-650 CFM. The flow rate shall be at least twice the drying
airflow rate.
Air exchange in a conventional pan can be improved by use of
strunck immersion tube or glatt immersion sword process
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22. Spray system
Solution or suspension may be sprayed into the pan
either by pneumatic (air spray) or hydraulic (airless
spray).
Pneumatic system.
Hydraulic system.
Variety of spray pattern is possible depending upon
design of the spray gun nozzle. The gun should be
positioned so that spray is applied perpendicular to
moving bed. The distance of 9-12 inches from the bed
is optimum.
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23. Powder delivery system
Accurate feeding of active & or dusting powder is a vital part
of many Pelletization process
Two major types are feeders used in conjunction with
coating pans, volumetric & weight feeder.
Volumetric feeders are designed to deliver a precise volume
of powder per unit of time
Weight feeders or loss-in-weight feeders have a counter
balanced scale under the base of feeder that measures the
weight loss during powder delivery.
Regardless of the type of delivery, it may be necessary to
add the glidant such as silicon dioxide to the powder to
prevent rat-holding or bridging in the feeder.
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24. Operational capabilities
Conventional pans are used for one or more of the
following step in Pelletization
Addition of drug as a dry powder onto an inert
substrate
Formation of pellets starting from dry drug
granules or crystals
Addition of drug into a form of solution or
suspension onto an inert substrate
Addition of an outer controlled release layer to
drugs – layered pellets
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25. Modified pans
Modified pans are much more efficient than conventional
pans due to improved air flow &superior bed mixing.
Modified pans can be used successfully for pellet coating.
Special features such as reversible airflow system, self
contained cleaning & air handling system and automated
product discharge system are available in many units
Explosion proof pneumatic control panel, microprocessor
system & complete spray system are standard features in
most of the modified pans.
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26. Modified Conventional Coating Pans
 Pellegrini coating pan
It features an angular pan that is rotated
on a horizontal axis.
Two types of air handling system are
available
In GC system hot, filtered air is blown
from back of the pan through bed & is
exhausted by means of two immersion
swords.
In PLC system drying air is partially blown
over the surface of bed & partially inside
the bed through a tube.
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27. ACCELA-COTA.
It differ from pellegrini pan in that he
periphery of the pan is completely
perforated.
The drying air enter from above & is
exhausted through a stationary
plenum that almost covers the entire
bed.
The pans are equipped with two to
six baffles depending upon the size.
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28. HI-COATER
• It is based on a design that has four
perforated segments each located at
90° to one another in the cylindrical
region of the pan.
• Each of these perforated sections acts
as the opening to an exhaust air.
• The 2mm perforations can be covered
by screens to allow for pellet coating .
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29. DRIACOATER
• Driacoater introduces drying air
through hollow perforated ribs
located on the inside periphery of
the drum.
• As the coating pan rotates, the ribs
into the bed, and drying air passes
up through the fluidizes the bed.
• Exhaust is from the back of the pan.
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30. GLATT PAN-COATING EQUIPMENT
It is similar to accela-
cota .
Angular pan has
perforations completely
around the periphery.
4 mm perforations can
be covered by screen to
allow for pellet coating
operation
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31. DUMOULIN COATER
These are latest modified pans.
They have perforation drum like
accela-cota.
Drying air can be introduced
from the top & or bottom & is
exhausted out the top.
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32. FLUID BED EQUIPMENT
The introduction of expansion space between the product container
& the filter chamber & the inclusion of a liquid spray nozzle in that
space give rise to fluid bed agglomeration.
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33. 33

34. Air handling system
Air handling unit can be designed to provide control over the temperature &
humidity of the process airstream result in improved reproducibility.
The most generally accepted mean for producing airflow in fluidized bed
machine is suction.
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35. Conditioning of process air
a) Simplest air handler:-includes prefilters & simple heat
exchanger with modulating steam value to control heating
medium
b) Face & bypass system:- this employs a set of dampers that
permit mixing of the airstream passing over the heat
exchanger with a bypass air stream
c) Dehumidification:- humidity of the system adjusted to
maximum desired level.
d) Humidification:- when combined with dehumidifier absolute
control is attained over the dew point of the process
airstream.
e) Bypass loop:- it allows the process air to bypass the product
until it reaches preset temperature & humidity parameters.
35

36. Product processing components
1 ] fluid bed dryers
Consists of product container to hold the unfluidized product , an
expansion zone into which product may be fluidized & filter section to
separate entrained particles of product from exiting process air stream.
As product dries more & more fine particle will be trapped in the
exhaust air filters and so the expansion space should be high enough to
minimize the no. of filter cleaning cycle during batch.
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37. 37

38. 2 ] fluid bed granulator
Expansion space is increased over the 50% of the height of dryer
expansion chamber.
Most significant difference is addition of liquid spray nozzle in expansion
area. Binding liquid is sprayed in a controlled rate to convert fluidized
powder into pellets
Product container should be deeper & narrower than FBD.
A product temperature sensing device is important in granulating
processes.
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39. 39

40. 3 ] fluid bed top spray coater
It is a method for applying liquid material in a
counter-current manner to the fluidized particles or
pellets.
Spray nozzle is located lower in the expansion
chamber so that liquid is applied to the when a
particle are moving at a high velocity. It inhibit surface
wetting & particle agglomeration.
Major difference with FBD is filter & its clearing
mechanism.
In coating operation it is prepherable not to interrupt
fluidization. So coaters are normally equipped with
multiple filters.
40

41. 41

42. 4 ] fluid bed bottom spray ( wurster ) coaters
The wurster coating chamber is cylindrical in shape &
contains an inner cylindrical partition normally one half
the diameter of outer chamber.
The liquid spray nozzle is located in center of orifice plate
& the partition is positioned above the plate to allow
movement of material from outside the partition to the
higher velocity airstream located inside the partition.
This design creates a very organized flow of product with
upward motion through the partition into the expansion
area & a downbed of particle in a near weightless
suspension outside the partition.
There are three types of design as type1,2 &3.
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43. 43

44. Exhaust air systems
1 ] outlet air filters
Selection of filter should be such that, maximum
retention of product & sufficient permeability to
permit adequate airflow.
2 ] exhaust fan or turbines
Usually turbines are fixed external to the building to
prevent inside noise & asses for maintenance & in
controlling discharge of turbines.
In case of particulates fluid dust collector may be
required.
44

45. Liquid spray nozzles
1 ] hydraulic nozzles
Commonly used in film coating especially when volatile organic
solvents are involved.
Droplet size is a function of nozzle orifice size, spray rate &
liquid line pressure.
2 ] ultrasonic nozzles
 liquid is supplied at low pressure & droplet are formed by
ultrasonic frequency at the discharge tip of the nozzle. This
frequency is a function of nozzle design & power source
3 ] air atomizing nozzles
 it uses air pressure & volume to produce droplets from liquid
that is supplied at low pressure.
The advantage is ability to control droplet size independently
of flow rate.
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46. Product discharge system
1 ] movable product container
 the most traditional method of charging & discharging of product in
dryer, granulator or top spray coater employs the use of movable
product container.
2 ] vacuum discharge
3 ] bottom dumping
The container stays in the machine & bottom plates open to allow the
material to fall out of the container.
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47. Solvent recovery system
1 ] Solvent scrubbing- eliminates the solvent
a) Absorption
b) Adsorption
c) Combustion
2 ] solvent recovery-collect the solvent for disposal or reuse
a) Once-through system
b) Closed loop system
47

48. CENTRIFUGAL EQUIPMENT
It is the newest & most advance means of producing pellets.
Advantages:-
Lower manufacturing cost
Flexibility in operation
Ease of automation
Disadvantages :-
Higher capital & installation cost
48

49. General equipment description
• It consists of many of the
same system components
that of fluid bed unit such as
air handling system, product
chamber, expansion
chamber, filtration device,
spray system as well as
safety& control systems.
• The uniqueness of centrifugal
processing equipment lies
mainly in use of rotating disc.
49

50. • Three forces centrifugal, gravitational & fluidization air act
upon the product from different direction.
• The rotating disc provide a centrifugal force which forces the
pellets toward the wall of the processing chamber at the
periphery of the rotor.
• Fluidized air provides via a slit, a vertical force that punches the
particle upward. As the airflow above the slit relaxes with
distance, particle cascade down towards the bottom of the disc
by gravitational force.
• The centrifugal force is a function of the rotational speed of the
disc. While the vertical distance the particle traverse depends
on air velocity & volume.
• The combined action of the three forces generate a spiral rope
like material motion & a rapid turnover rate that is responsible
for high efficiency of centrifugal equipment.
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51. • Another distinct feature is its spray method
• The spray guns are generally immersed in the product & liquid is sprayed
tangentially to the rotating pellet bed. That is liquid is applied
concurrently in the direction of pellet movement.
• This design partially account for reproducibility & efficiency of process.
• These machine also provides the direct application of powder to product
bed.
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52. Specific equipment description
CF granulator
1) Product chamber
2) Product discharge
3) Powder delivery
4) Liquid spray
assembly
5) Air supply system
6) Control panel
7) Automatic humidity
feedback system
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53. 53

54. Glatt rotor granulator
1) Product container
2) Powder delivery
3) Air handling & exhaust
system
4) Expansion chamber
5) Product discharge
6) Spray system
7) Control panel
54

55. Roto processor
1) Product
container
2) Powder delivery
devices
3) Product
discharge
4) Control system
5) Air supply &
exhaust system
55

56. Spir-a-flow
1) Product chamber
2) Product charging &
discharging
3) Spray system
4) Powder delivery
device
5) Expansion chamber
56