Content :-

● Definition of pellets
● Advantages And
Disadvantage
● Formulation requirment
● Pelletization process
● Equipments for
manufacture of pellets
Pellet:- pellets can be defined as small, free-flowing, spherical particulates
manufactured by the agglomeration of fine powders or granules of drug substances and
excipient using appropriate processing equipment[4]

Pharmaceutical advantages:
∙ Uniformity of dose
∙ spheres have excellent flow properties
∙ Prevention of dust formation
∙ Controlled release application of pellets due to the ideal low surface area-to-volume
ratio.
Disadvantage:
1. It is difficult to compress pellets into tablets as they are too rigid. Therefore, they are
often delivered encapsulated in hard gelatin capsule shells.
2. Pelletization demands highly sophisticated and specialized equipment, thereby
increasing the cost of manufacturing
.3.The control of manufacturing process is complicated with too many process variables
as well as formulation

Formulation
1. Active Pharmaceutical Ingredient.
2. Binder: They are also called as agglomerating inducers or bridging agents. These are
adhesive materials that can be incorporated into pellet formulations to bind powders and
maintain integrity on pellet formation and the addition of the binder may be as a solution
than the dry form, which is considered to be more efficient than dry mixing following liquid
addition. E.g- Gelatin, sucrose and starch
3. Granulating fluid: Moisture content of the wet mass prepared is the most crucial
parameter for pellet growth as it imparts the required plasticity and cohesiveness to the wet
mass to extrude
 it and spheronize it to give a prefect spherical shape. examples are alcoholic or hydroalcoholic
systems, ethyl ether, dilute acetic acid, isopropyl alcohol
4. Spheronizing Enhancer: Spheronization enhancers are formulation aids that improve the
production of spherical pellets, mainly during spheronization and balling processes. They not only
impart plasticity onto the formulation, but also impart binding properties that are essential for
pellet strength and integrity.e.g- MCC ,sodium CMC
5. Filler: These are the excipients used to form the bulk of the material, in the process of
pelletization 70 to 80% of the excipients is formed by fillers. Generally microcrystalline
cellulose is used for this purpose. Avicel PH 101 is considered to be the pelletization aiding
excipient in this process. Glyceryl mono stearate (GMS), Starch RX1500, spray dried lactose.
6. Plasticizer: Plasticizers improve the flexibility of polymers by reducing the tensile strength and
glass transition temperature of the material. examples are Glycerol, Propylene glycol, low
molecular weight polyethylene glycols, phthalate derivatives like dimethyl, diethyl and dibutyl
phthalate
7. Lubricant: In pelletization process, lubricants are rarely used as the high-speed rotary
equipments are being used in the preparation of pellets. However, during compression and
Extrusion-Spheronization, lubricants do play a crucial role in the successful manufacture of
pellets. Their use reduces the friction between the die wall and material mix either during the
compression process or in ejection phase.E.g- Calcium stearate, glycerin, PEG, Mg. Stearate
8. Separating Agents: Separating agents are materials which are adsorbed on the surface and
promote the separation of pellets into individual units during a pelletization process, which are
incorporated initially in the formulation or externally during processing to prevent pellets
attracting one another due to surface charge development during the process.E.g- Kaolin, talc,
silicon dioxide
9. Surfactant: In most pelletization processes, the initial pellet formation and subsequent growth
into fully fledged smooth surfaced spherical pellets depends, to some extent, on the liquid
bridges that hold the primary particles together, therefore, liquid (water in most cases) wetting
the particles effectively is given more attention. Surfactants are added to the liquid to improve
wettability by lowering the interfacial tension between the liquid and drug particles
10.Flavoring agent: The choice for the flavors changes from individual to individual
depending upon the age, ethnicity and liking which plays a significant role in the taste
fondness.
11. Sweetening agent: The sweet taste in formulation is more preferred especially in case of
pediatric population. Natural sweeteners as well as synthetic sweeteners are used to improve
the palatability of the formulations. The traditional source of sweetener is sucrose (derived
from
cane or beet in the form of liquid or dry state), dextrose, fructose, glucose, liquid glucose and
maltose.
12.Coloring agents: Coloring agents are generally used in order to improve the
appearance and
make it more patient compliance. Pigments such as Titanium dioxide or FD&C approved coloring
agents are used either in the dry form or mixed with the granulating fluid during the formulation.

Pelletization process : It involves three consecutive regions:

∙ Nucleation
∙ Transition and
∙ Ball growth.
However, based on the experiments on the mechanism of pellet formation and growth, the
following steps were proposed: nucleation, coalescence, layering and abrasion transfer

Nucleation:
∙ Nucleation is a stage of Pelletization process that occurs whenever a powder is wetted
with solvent system. The primitive particles are drawn together to form three-phase air-
water-liquid nuclei system which are held together by liquid bridges that are pendular in
nature.
∙ Further the size, the rate and the extent of nuclear formation depends upon the size of the
particles, the moisture content, the viscosity of the binding particles, the wettability of the
substrate and the processing conditions, such as tumbling and drying rates.
Transition phase:
∙ Nucleation is followed by a transition phase where the growth mechanisms affecting are
coalescence and layering. Coalescence is defined as the formation of large-sized particles
by random collision of well-formed nuclei, this mechanism require slightly excess
moisture on the surface of the nuclei although the number of nuclei is progressively
reduced even though the total mass of the system remains unchanged during this
operation.
∙ Coalescence causes discrete size changes and leads to decrease in number of
agglomerates but not their mass
∙ Layering is a slow growth mechanism and with the successive addition of fragments and
fines on an already formed nuclei.
∙ The fines and the fragments produced through size reduction are taken up by larger
pellets. Production of fines and subsequent coalescence and layering continues until the
number of collisions declines rapidly, thereby leading to a reduction in the rate of growth
of the pellets. At this point the third phase, the ball growth region, is reached.
Ball growth phase:
∙ The main mechanism in the ball growth phase is the abrasion transfer which involves the
transfer of materials from one granule formed to another without any preference in either
direction.
∙ This phase does not result in any change in the total number or mass of the particles.
However, the particles undergo a continuous change in their size as long as the conditions
that lead to the transfer of material exist.
Pelletization Techniques :
● Extrusion Spheronization
mixing of ingredients is done to achieve homogeneous powder dispersion using twin
shell blender, planetary mixer, high speed mixer and tumbler mixer
Wet Massing: Wet
massing is done to produce a sufficient plastic mass for extrusion, by employing(a)Dry Mixing:
normal
equipment and processes as employed in wet granulation for compaction. The Drymost
commonly used granulator is planetary mixer or Hobart mixer or sigma blade mixer and high
shear mixer
Extrusion: This is
the third step in the process, which produces rod shaped particles of uniform diameter from
the wet mass. The wet mass is forced through dies and shaped into small cylindrical particles
with uniform diameter.
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. During Spheronization process different stages can be distinguished
depending upon the shape
Drying: A drying
stage is required in order to achieve the desired moisture content. Drying rate also important
an increase drying rate gave more porous pellets due to decrease pellet densification during
that drying process
 Screening:
Screening may be necessary to achieve the desired size distribution, and for this purpose
sieves are used

∙
 ● Hot Melt Extrusion :
This method involves compaction and conversion of blend of powder into uniform shape
product. Polymers were melted and forced these polymers and active ingredients along with
other additives through an orifice or die that were placed under controlled temperature, pressure,
screw speed etc, to form products of different shapes and sizes. Whole process can be classified
into following steps:

1. Feeding of the extruder through a hopper

2. Mixing, grinding and kneading
3. Flow through the die, and
4. Extrusion from the die and further downstream processing

∙
Equipments for manufacture of pellet :

● Mixer like sigma blade mixer, hexagonal mixer

● Drying equipment like Fluidized Bed

Dryer,spray dryer Fluidized Bed processor

● Freez

drying

Spher

onizer

Coating pan, compression machine

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