Pellets

Pellets
• 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.
 Why pellets ?
• Taste masking: Micropellets are ideal for products
where perfect abatement of taste is required. pellets
provide 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
Potential lower daily cost to patient due to
fewer dosage units, in contrast the whole
tablet is 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 tablet dosage form separate
tablets would have to be administered, but the pellets
can be administered in a 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.
 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.
 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.
 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
• 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 irritant effect of some drugs on the
gastric mucosa.
Methods of Pelletization
 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.
 Extrusion-Spheronization
• The extrusion-spheronization process can be
broken down into the following steps:
 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
 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.
Hot melt extrusion
 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.
Hot melt extrusion
 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
 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.
 Fluid-Bed Granulation

Figure: Three Version of fluidized bed granulator.

A. Top-Spray Method
B. Bottom-Spray Method
C. Tangential-Spray Method
 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.
 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.
 Spray Drying
• A drug solution or suspension is sprayed, with
or without excipients, into a hot-air stream,
generating dry and highly spherical particles.
• Vitamin A and D can be coated by this process
to prevent their deterioration
Figure: Typical Spray-Drying System
 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
 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
surface 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.
 Liquid layering
• There are many factors that determine the economic and
performance feasibility 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.
 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 (inert 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.
Powder layering
 Cryopeletization
• Cryopeletization is a process where liquid
droplets or 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 to
freeze in block form which is difficult to
handle.
Dosage form development using
pellets
 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.
 Evaluation of Pellets
• Particle size analysis-Optical microscope, Sieve
analysis
• Surface morphology- SEM
• Surface roughness- Non contracting laser profile meter
• Micromeritic properties
• Friability – Erkewa type tablet friabiliator, tubula mixer
F=[1-W/W0]×100
W0=Initial weight
W=weight after 100 rotations
 Evaluation of Pellets
• Tensile strength
• Porosity-SEM, Mercury Porosimetry ,Optical
microscopy
• Crushing strength
• Percentage yield
• % Yield=wt. of pellets/wt. of drug + wt. of
polymers×100
 Evaluation of Pellets
• Disintegration time- USP Apparatus
3(reciprocating cylinder method)
• Determination of drug content-UV/VISIBLE
spectrophotometer
• Loose surface crystal study (LSC)-200mg
pellets+100ml of phosphate buffer(7.4).Amt
of dg present in solution can be analyzed by
spectrophotometrically.
 Marketed product
Example of Tablets & Capsules:
• Amoxicillin
• Pseudoephedrine
• Propranolol HCL
• Esomeprazole
• Omeprazole
• Lansoprazole
• Niacin
• Duloxetine HCL
• Prochlorperazine
• Phendimetrazine tartrate
Marketed product
 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
advantage over 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 and topical delivery systems.