PELLETS

By:
Dr. Amitha Shetty
Assistant Professor
NGSMIPS

NGSM Institute of Pharmaceutical Sciences

 INTRODUCTION
WHAT ARE PELLETS?

✓ In the pharmaceutical industry, PELLETS can be defined as

small, free-flowing, spherical particulates manufactured
by the agglomeration process of bulk drugs and excipients
using appropriate processing equipment and the process is
known as PELLETIZATION

✓ Formation of spherical beads or pellets with a mean

diameter ranging from 0.5 to 2.0 mm.

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NGSM Institute of Pharmaceutical Sciences
PELLETIZATION VS. GRANULATION

✓ Terms “granulation” and “pelletization” are sometimes used

synonymously and no clear distinction is made between
them

✓ If agglomerates size distribution is within 0.1 - 2.0 mm and

high porosity (20 - 50 %), --- GRANULATION

✓ If agglomerates have narrow size range, 0.5 - 2.0 mm and

have low porosity (10 %) with free flowing properties ---
PELLETIZATION
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 ADVANTAGES

TECHNOLOGICAL ADVANTAGES

✓ Improvement of uniformity of the content

✓ Prevention of dust formation

✓ The defined shape and weight improves the appearance

✓ Improvement in the handling due to free-flowing

properties

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 ADVANTAGES… cont…

THERAPEUTIC ADVANTAGES

✓ Pellets can disperse freely throughout an area of the

gastrointestinal tract

✓ Pellets reduce peak plasma fluctuations and minimize

potential side effects

✓ Avoiding the irritant effect of some drugs on the gastric mucosa

✓ Modified-release multiparticulate delivery systems are less

susceptible to dose dumping than single-unit dosage forms
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 DISADVANTAGES

✓ Often pellets cannot be pressed into tablets because they

are too rigid.

✓ The production of pellets is often an expensive process and

/ or requires highly specialized equipment.

✓ The control of the production process is difficult (e.g. the

amount of water to be added is critical for the quality of the
pellets and over wetting can occur very easily).

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 FORMULATION

1. Fillers
2. Binders
3. Separating agent
4. Disintegrant
5. Surfactants
6. Spheronization enhancers
7. Lubricants
8. Glidants

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1. Fillers:
✓ Fillers are added to increase bulk properties

✓ Fillers are water soluble or insoluble in nature

✓ The use of fillers based on characteristics of drug, method of

preparation and required dose

✓ The amount of fillers used in formulation as high as 90% or as

low as 1%

✓ The quantity and physical properties may affect the desired

formulation’s rate and extent of drug release from pellets

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2. Binders:
✓ Binders are use to integrate and bind the powder for pellet
formulation by adhesive nature of it

3. Separating agent:
✓ During pelletization process separating agents absorbs on
surface to promote separation of pellets into individual unit

✓ Pellets promote surface charge during manufacture and may

lead to attract one another

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4. Disintegrant:

✓ Are suitable to add in formulation at any step of process,

particularly to granulation or during lubrication step prior
to compression

✓ These are substances which in presence of fluid break up

the compacted mass of solid dosage form

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5. Surfactants:

✓ Surfactants are generally used in pellet formulation mainly

for same reason they used in other various dosage forms

✓ The poorly soluble drug have improved solubility,

wettability and enhance dissolution rates

✓ The initial and subsequent growth of pellets depends on

formation of liquid bridges to hold particles together that
means lowering surface tension may leads to weaken
bridges and forming pellets

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6. Spheronization enhancers:

✓ These formulation aids are used to develop a spherical

pellets

✓ These substances impart binding properties to pellets for

it’s strength and integrity

7. Lubricants:

✓ Lubricants are used in pellet formulation to reduce the

friction between manufacturing equipment and particles

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8. Glidants:

✓ These are used to develop a flow characteristics

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PELLETIZATION TECHNIQUE

Extrusion /
Spheronisation
Hot-Melt Fluid-bed
Extrusion Granulation

Rotogranulation
Cryopelletization PELLETIZATION
TECHNIQUE

Solution and
Suspension
Spray- Layering
congealing

Spray- Dry Powder

drying Layering

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1. EXTRUSION / SPHERONISATION:

✓ Extrusion / spheronisation is a multistage process for

obtaining pellets with uniform size from wet granulates
(extrudates)

✓ Steps involved in Extrusion-Spheronization:

1. Dry Mixing:

✓ Dry mixing of ingredients is done to achieve homogenous

powder dispersion using Twin shell blender, Planetary
mixer, High speed mixer and Tumbler mixer.

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2. Wet massing:

✓ It is done to produce a sufficient plastic mass for

extrusion, by employing normal equipment and process
as employed in wet granulation for compaction.

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3. Extrusion:

✓ It produces rod shaped particles of uniform diameter

from wet mass.

✓ The wet mass is forced through dies and shaped into

small cylindrical particles with uniform diameter.

✓ Such shaping of wet mass into long rods, commonly

termed ‘EXTRUDATE’.

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4. Spheronization:

✓ Consists of a static cylinder and a rotating friction plate

where the extrudate is broken up into smaller cylinders
with a length equal to their diameter and these plastic
cylinders are rounded due to frictional forces

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5. Drying:

✓ A drying stage is required in order to achieve the desired

moisture content.

6. Screening:

✓ It is necessary to achieve the desired size distribution, and

for this purpose sieves are used.

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✓ EXTRUSION

✓ Applying pressure to a wet mass until it passes through

the calibrated openings of a screen or die plate of the
extruder and further shaped into small extrudate
segments

✓ As the mass passes through the extruder screen, the

resulting extrudates eventually break under their own
weight

✓ Usually the extrudates have the same length

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✓ In order to obtain reproducible results, it is recommended
to monitor extrusion parameters such as:

➢ feed rate,

➢ powder consumption,

➢ die temperature and

➢ compression chamber pressure.

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 Types of extruder:

Screw extruder Gravity-fed

Ram Extruders
extruders

• Axial extruders • Rotary

Cylinder
• Radial Extruder
extruders
• Rotary-Gear
Extruder

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1. Screw extruder:

✓ Uses a screw to generate the pressure needed to thrust the

material to flow

✓ Material will flow via equal openings, forming identical

strands, commonly referred to as extrudates.

✓ Employs single or twin helical screws spinning in a barrel.

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✓ It transfers the damp mass material from a feeder hopper
to the die section

✓ The die comprises of a thin steel plate punctured with

numerous holes that can be positioned either axially or
radially to the screw feed

✓ Thus screw extruder may be of two types:

a. Axial extruders

b. Radial extruders
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a. Axial extruders:

✓ These have a die plate that is positioned axially, consist of

a feeding zone, a compression zone, and an extrusion zone

b. Radial extruders:

✓ The transport zone is short, and the material is extruded

radially through screens mounted around the horizontal
axis of the screws

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NGSM Institute of Pharmaceutical Sciences
2. Gravity-fed extruder:

✓ These are of two types, which differ primarily in the design

of the two counter-rotating cylinders:

a. Rotary Cylinder Extruder

b. Rotary Gear Extruder

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a. Rotary Cylinder Extruder:

✓ One of the two counter-rotating cylinders is hollow and

perforated, where as the other cylinder is solid and acts as
a pressure roller

b. Rotary Gear Extruder

✓ There are two hollow counter-rotating gear cylinders with

counterbored holes

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NGSM Institute of Pharmaceutical Sciences
3. Ram extruder:

✓ The ram extruder is probably the oldest type of extruders;

a piston displaces and forces the material through a die at
the end

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✓ SPHERONISATION:

✓ Also known as marumerizer

✓ Spheronisation refers to the formation of spherical

particles from the small rods produced by extrusion

✓ The size of the spheres are determined by the diameter of

the extrudate used for the spheronization process

✓ For example, in order to obtain spheres with a diameter of

1 mm, a 1 mm screen is used on the extruder

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✓ DESIGN:

✓ Basic machine consists of a rotating friction disk,

designed to increase friction with the product, which spins
at high speed at the bottom of a cylindrical bowl

✓ Spinning friction disc has a carefully designed groove

pattern on the processing surface

✓ This is most often crosshatched, but several sizes and other

types are available

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NGSM Institute of Pharmaceutical Sciences
✓ Working

✓ To form spheroids, extrudates are brought onto the rotating

friction plate of the spheronizer, which imparts a rolling
motion to the material

✓ Following the collisions between extrudates with each other

and with the friction plate and the stationary walls of the
spheronization chamber, the cylindrical segments change
their shape and size

✓ Transition from cylindrical segments to spheres occurs in

several stages

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NGSM Institute of Pharmaceutical Sciences
2. FLUID-BED GRANULATION:
✓ The process is carried out continuously in a fluid-bed
granulator

✓ The fluid-bed granulation is performed following these steps:

a. Pre-blending of the formulation powder, including the active

ingredients, fillers, disintegrant in a flow of air

b. Granulation of the mixture by spraying a suitable liquid

binder onto the fluidized (suspended) powder bed

c. Drying of the granulated product to the desired moisture

content
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✓ Three version of fluidized bed granulator:

a. Top-Spray Method

b. Bottom-Spray Method

c. Tangential-Spray Method

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NGSM Institute of Pharmaceutical Sciences
NGSM Institute of Pharmaceutical Sciences
3. ROTO-GRANULATION:

✓ Roto-granulation is one of the most recent methods for the

production of spheroids

✓ The single-unit spheronizing system can be described using

terms like centrifugal granulator, rotary fluidized-bed
granulator, rotary fluid bed, rotary processor or rotor
granulator

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✓ Regardless the name of the equipment, they all have the
same main piece, a rotating disc

✓ When the equipment is operating, this disk provides a

centrifugal force which throws the pellets towards the
wall of the processing chamber

✓ As the fluidizing force decreases with the distance above

the slit, the pellets fall towards the bottom of the disc

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NGSM Institute of Pharmaceutical Sciences
4. SOLUTION AND SUSPENSION LAYERING:

✓ Involve the deposition of successive layers of solutions

and suspensions of drug substances, respectively, on
starter seeds that may be inert materials or crystals or
granules of the same drug

✓ These characteristics are especially desirable when pellets

will be coated for the purpose of achieving a controlled
release

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✓ The equipment employed for this kind of processes consists
of custom modified conventional coating pans (perforated
pans) and various configurations of fluid-bed equipment

✓ During solution or suspension layering, all the components

of the formulation are dissolved or suspended in the
application medium

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✓ As the solution or suspension is sprayed onto the product bed,
the droplets impinge on the starter seeds or cores and spread
evenly on the surface

✓ This is followed by the drying phase which allows dissolved

materials to crystallize and form solid bridges between the
core and initial layer of the drug substance as well as among the
successive layers of drug substance

✓ The process continues until the desired layers of drug and

hence the target potency of the pellets are achieved

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NGSM Institute of Pharmaceutical Sciences
5. DRY POWDER LAYERING:

✓ This process is similar to the solution or suspension layering

✓ Instead of these dispersions, the layering is performed using

a drug powder

✓ Usually, the process is carried out in conventional coating

pans

✓ After the wet seeds pick up the powder, they are directed
back into the upward moving bed and the entire process is
repeated

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✓ In an intermittent powder layering process, the layering
solution is added until the bed is wet and tacky

✓ The drug powder is then added, until the bed is dry

✓ Warm drying air may be used after each cycle

✓ The process continues until all of the drug powder has

been added

✓ In a continuous process, the layering solution and the drug

powder are added simultaneously
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NGSM Institute of Pharmaceutical Sciences
6. SPRAY-DRYING:
✓ During spray-drying, a drug solution or suspension is
sprayed, with or without excipients, into a hot-air stream,
generating dry and highly spherical particles

✓ The spray-dried powder particles are homogenous,

approximately spherical, nearly uniform in size

✓ The design and operation of the spray drier can influence a

great number of characteristics of the final product, such as
particle size and size distribution, bulk density, porosity,
moisture content, flow-ability
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NGSM Institute of Pharmaceutical Sciences
7. SPRAY-CONGEALING (Spray Chilling):
✓ It is a technique similar to spray-drying

✓ Spray congealing is a process in which a drug is allowed to

melt, disperse or dissolve in hot melts of gums, waxes, fatty
acids or other melting solids

✓ The dispersion is then sprayed into stream of air and other

gases with a temperature below the melting point of
formulation components

✓ Under appropriate processing conditions, spherical congealed

pellets are obtained.
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NGSM Institute of Pharmaceutical Sciences
8. CRYOPELLETIZATION:
✓ Pellets are produced by allowing droplets of liquid
formulation like solution, suspension or emulsion to come in
contact with liquid nitrogen at -160˚C in which liquid
nitrogen used as solidifying medium

✓ The procedure permits freezing of the material being

processed due to rapid heat transfer that occurs between the
droplets and the liquid nitrogen

✓ The pellets are dried in conventional freeze dryers to

remove water or organic solvents
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9. HOT MELT EXTRUSION (HME):
✓ It is process of pumping raw materials with a rotating
screw under elevated temperature through a die into a
product of uniform shape

✓ HME process is divided in to four sections namely:

a. Feeding of extruder,

b. Conveying of mass [mixing and reduction of particle size],

c. Flow through the die and

d. Exit from the die and downstream processing

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NGSM Institute of Pharmaceutical Sciences
PELLETIZATION TECHNIQUE

Extrusion /
Spheronisation
Hot-Melt Fluid-bed
Extrusion Granulation

Rotogranulation
Cryopelletization PELLETIZATION
TECHNIQUE

Solution and
Suspension
Spray- Layering
congealing

Spray- Dry Powder

drying Layering

NGSM Institute of Pharmaceutical Sciences

 MCQ

1. In which method liquid nitrogen is used for the preparation

of pellets?

A. Extrusion / Spheronisation

B. Rotogranulation

C. Cryopelletization

D. Hot-Melt Extrusion

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 MCQ

2. Which method is also known as marumerizer?

A. Extrusion

B. Spheronisation

C. Hot-Melt Extrusion

D. Rotogranulation

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 5 MARKS

1. Write the merits and demerits of Pellets.

2. Discuss the formulation requirement for pellet.

3. Explain Extrusion and Spheronisation.

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NGSM Institute of Pharmaceutical Sciences