2. Pharmaceutical Pellets
What is pellet?
Small free flowing spherical
units ranging in size, prepared
by agglomeration of fine
powders called pellets.
• Their size and shape allow
their administration as
injections and also for oral
drug delivery.
• Pellets range in size,
typically, between 0.5 –
1.5 mm, though other sizes
could be prepared.
3. Why pellets ?
• Taste masking: Micropellets are ideal for products where
perfect abatement of taste is required. pellets proivide the
masking of unpleasant taste without lowering of bioavailability
especially for oral products.
• Immediate release: Administering drugs in pellet form leads to
an increased surface area as compared to traditional
compressed tablets and capsules. This would considerably
reduce the time required for disintegration and have the
potential for use in rapidly dispersible tablets.
• Sustained release: Pellets are being increasingly used in the
manufacture of sustained release dosage form of drugs. The
advantages of the dosage form is well known and some
examples are given below :
• Extend day time and night time activity of the drugs,
• Reduced dosage frequency of dosage forms,
• Increased patient compliance
4. • Potential lower daily cost to patient due to fewer dosage units,
in contrast the whole tabletis released at once in to the small
intestine as the stomach empties itself
• Different types of polymers are utilized for coating of different
drugs to enable the sustained release/controlled release rate of
drugs.
Chemically incompatible products: At times such ingredients are
required to be delivered in a single dose. In the compressed
tabletdosage form separate tablets would have to be
administered, but the pellets can be administered ina single
capsule.
• Varying dosage without reformulation
• Pellets have excellent flow properties, due to this, they can be
conveniently used for filling capsules and the manufacturer can
vary the dosage by varying the capsule size without
reformulating the product
• Pelletization is an agglomeration process that converts fine
powders or granules of bulk drugs and excipients into small, free
flowing semi-spherical units.
5. MECHANISM OF DRUG RELEASE FROM MULTI-
PARTICULATES
Diffusion :- On contact with aqueous
fluids in the gastrointestinal tract
(GIT), water diffuses into the interior
of the particle. Drug dissolution
occurs and the drug solutions diffuse
across the release coat to the
exterior.
Erosion :- Some coatings can be
designed to erode gradually with time,
thereby releasing the drug contained
within the particle.
Osmosis :- In allowing water to enter
under the right circumstances, an
osmotic pressure can be built up within
the interior of the particle. The drug
is forced out of the particle into the
exterior through the coating.
6. Advantages of Pellets
• Improved aesthetic appearance of the product.
• Coating of drug pellets with different polymers to achieve
controlled release rate of drugs.
• For immediate release products large surface area of the
pellets enables better distribution, dissolution and
absorption.
• Chemically incompatible products can be formulated into
pellets and delivered into single dosage form by encapsulating
them.
• Pellets ensures improved flow properties and flexibility in
formulation, development , and manufacture.
7. RESONS FOR PELLETIZATION
• Prevention of segregation of co-agglomerated
• Improvement of the process safety, as fine powders can cause dust
explosions and the respiration of fines can cause health problems
• The defined shape and weight improves the – appearance of the
product
• Controlled release application of pellets due – to the ideal low
surface area-to-volume ratio that provides an ideal shape for the
application of film coatings.
• pellets can disperse freely throughout an area of the
gastrointestinal tract after administration and consequently the
drug absorbtion is maximized as a large gastrointestinal surface can
be involved in this process
• peak plasma level of the drug can be reduced – by the use of
spherical particles with different release rates;
• potential side effects are minimized without markedly lowering drug
bioavailability;
• the wide distribution of spherical particles in the gastrointestinal
tract limits localized build-up of the drug, avoiding the irritand
effect of some drugs on the gastric mucosa;.
9. Extrusion or Spheronization
• Extrusion spheronization is widely utilized in
formulation of sustained release, controlled release
delivery system.
• The main objective of the extrusion spheronization
is to produce pellets/spheroids of uniform size with
high drug loading capacity
11. Extrusion Spheronization
Product features
• Dust free
• High spherocity
• Free flowing
• Compact structure
• Low hygroscopicity
• High bulk density
• Low abrasion
• Narrow particle size distribution
• Smooth surface
12. Hot melt extrusion
• Hot melt extrusion is a process of
converting raw material into a product
of uniform shape and density by
forcing it through a die under
controlled condition.
14. Hot melt extrusion
• The theoretical approach to understanding the melt
extrusion process is therefore, generally presented by
dividing the process of flow into four sections:
• 1) Feeding of the extruder.
• 2) Conveying of mass (mixing and reduction of
• particle size).
• 3) Flow through the die.
• 4) Exit from the die and down-stream processing.
16. Hot melt extrusion
Applications in the pharmaceutical industry:
In pharmaceutical industry the melt extrusion has been
used for various purposes, such as
1. Improving the dissolution rate and bioavailability
of the drug by forming a solid dispersion or solid
solution.
2. Controlling or modifying the release of the drug.
3. Masking the bitter taste of an active drug
17. Granulation
Wet Granulation
The process of adding a liquid solution to powders involves the
massing of a mix of dry primary powder particles using
a granulating fluid. The fluid contains a solvent that must be
volatile.
Meets all the physical requirements for compression of
tablets.
Fluid-bed Granulation
The process is carried out continuously in a fluid-bed
granulator.
Spraying of a granulation solution onto the suspended
particles, which then are
dried rapidly in the hot air stream.
18. Fluid-Bed Granulation
Figure: Three Version of fluidized bed granulator.
A. Top-Spray Method
B. Bottom-Spray Method
C. Tangential-Spray Method
19. Fluid-Bed Granulation
The fluid-bed granulation is performed following these
steps: ( Tangential-Spray Method )
Pre-blending of the formulation powder, including the
active ingredients, fillers, disintegrants, in a flow of air.
Granulation of the mixture by spraying a suitable liquid
binder onto the fluidized (suspended) powder bed.
Drying of the granulated product to the desired moisture
content.
Parameters
Equipment parameters
Product parameters
Process parameters
Advantages over traditional wet granulation
Automated, performed in one unit, thus saving costs,
transfer losses and time.
Fluid bed granulation process improves the dissolution
efficiency of both nimodipine and spironolactone tablets.
20. Fluid-Bed Granulation
Figure: Dissolution Efficiencies of Nimodipine and Spironolactone.
Melt Granulation
Granulation is achieved by the addition of meltable
binder.
Binder is in solid state at room temperature but
melts in the temperature range of 50 – 80˚C. e.g.
Polyethylene Glycol (PEG) 2000, 4000, 6000, 8000 (40-60 0C)
Melted binder then acts like a binding liquid.
No need of drying phase since dried granules are
obtained by cooling it to room temperature.
21. Spray Drying
A drug solution or suspension is sprayed, with or without
excipients, into a hot-air stream, generating dry and
highly spherical particles.
Figure: Typical Spray-Drying System.
Vitamin A and D can be coated by this process to prevent
their deterioration
22. Spray Congealing
Also called Spray-Chilling, a technique similar to Spray-Drying but
no source of heat is required
Drugs can be suspended in molten wax and can give sustain release
effect
Monoglycerides and similar components are spray-congealed
Figure: Spray-Congealing.
23. Layering technique
• layering involves the deposition of successive layers of dry
powder or liquid droplets of drug with excipients and binding
liquid on to starting inert seed .
• Liquid layering: Liquid layering of pellets involves the
deposition of successive layers of solutions or suspensions of drug
substances and binders on starter seeds, which may be inert
materials and that produce pellets with uniform size distribution
and very good surphace morphology that then dried
simultaneously.
• These characteristics are especially desirable in development of
controlled release pellets.
• Custom modified conventional coating pans (perforated pans) and
various configurations of fluid-bed equipment used to achieve this.
24. Liquid layering
There are many factors that determine the
economic and performance feasability of
pellet coating such as drug solubility used in
solution layering, suspension concentration in
suspension layering and particle size of
suspension.
Micronized drug particles tend to provide
pellets that are smooth in appearance.
If the particle size of the drug in the
suspension is large, the amount of binder
required to immobilize the particles onto the
cores will be high, and, consequently, pellets
of low potency are produced.
The morphology of the finished pellets also
tends to be rough and may adversely affect
the coating process and the coated product.
25. Powder layering
• It is layering a drug onto starter
pellets. When the active ingredient is
in powder form, pelletization can be
achieved by spraying starter pellets
with the active powder and at the same
time a liquid binder solution. The
layered pellets are then dried.
• OR,
• Initially, the starter seeds (innert
pellets, beads, spheres) are charged
into a rotating pan, then wetted by
spraying an adhesive solution. As the
wet seeds reach the front end of the
pan, the powder added in the vortex
adheres to them.
27. Cryopeletization
• Cryopeletization is a process
where liquid dropletsor powder
of a formulation converted
into solid spherical pellets by
using liquid nitrogen gas in a
fixed medium at -160°C
Application:
• It is used as an intermediate
holding step
• It is used for long-term
storage
• It enables ultra-fast freeze
drying
• It is used to halt a
fermentation reaction
Advantages of cryopelletization:
It is very easy to handle.
It produces free-flowing pellet
forms.
It offers ultra-fast thawing for
consistent and fast reconstitution
eliminating the need tofreeze in
block form which is difficult to
handle.
29. Modified release pellets
• Pellets may have one or more layers of different polymer with
suitable excipients for modified release of drug and then formulated
as tablet or capsule.
• The use of pellets coated with different polymers and different film
thicknesses that allow modulation of the release rate from pellets
over and extended period of time.
31. Conclusion
• The brief review on pellets &pelletization concludes
pelletized dosage forms as one of the most
promising &efficient pathway of novel &
multiparticulate Drug delivery System .This
pelletization technique has great advantageover the
single unit dosage form.Now-a-days,pelletization
tech.is used widely which are unstable drug or
have compatibility problem with excipients.The
potential of this technology provide the scope for
development of different oral controlled delivery
systems iand topical delivery systems.
32. Reference
• Remington : The Science and Practice of
Pharmacy
• http://www.jpsbr.org/volume_5/JPSBR_Vol_5
_Issue_1_htm_files/JPSBR15RS3013.pdf
• http://ijpr.sbmu.ac.ir/article_290_0.html
• http://ijpsr.com/bft-article/pelletization-
technology-a-quick-review/?view=fulltext
