PELLETS
AND INNOVATIONS IN
PELLETS
GUIDED BY:
Dr. M. C. GOHEL PRESENTED BY:
Dr. R. K. PARIKH VIVEK P PATEL
DEPERTMENT OF PHARMACEUTICS AND PHARMACEUTICAL TECHNOLOGY
[Link] OF PHARMACY-AHMEDABAD
LIST OF CONTENT
• Definition
• Characteristics properties of pellets
• Advantages and disadvantages of pellets
• Pelletization process
• Newer techniques
• Recent innovation
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (2/38)
What is
pellet?
Pellets are defined as small, spherical
particulates produced by the agglomeration of
fine powders or granules of drug substances
and excipients using appropriate equipments.
They are usually free flowing.
The size of pellets vary from formulation to
formulation but usually lies between 1 and 2
mm.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (3/38)
CHARACTERISTICS PROPERTIES
OF PELLETS
Uncoated pellets:
• Uniform Spherical Shape
• Uniform Size
• Good Flow Property
• Ease Of Packing (E.G. Into A Hard Gelatin
Capsule)
• High Mechanical Strength
• Low Friability
• Ease Of Coating
Coated pellets:
• All above and desired drug release characteristics
according to the type of coat material.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (4/38)
ADVANTAGES OF PELLETS
They can be dispensed as such, filled into a capsule as well
as can be compressed into a tablet.
They can be also used to dispense incompatible bioactive
agents together into a single formulation.
They can be divided into desired dose strengths without
formulation or process changes.
Different release profiles in a single formulation can be
met.
Release of drugs at different sites in the GIT.
Upon oral administration, they maximize absorption as they
freely disperse in GIT.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (5/38)
DISADVANTAGES OF PELLETS
If the pellets are volume filled, for example in capsules, it
may lead to the problems of content uniformity and
differences in dosing.
If the pellets are coated, then upon compression into a
tablet, there are chances that the coat of pellets may
rupture.
Pronounced surface roughness of pellets may hinder the
filling process.
If the pellets are coated with an ethyl cellulose film, the
batches could not be filled to an acceptable standard
because electro-static charges develop that lead to
blocking during the filling process.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (6/38)
PELLETIZATION PROCESSES
Direct palletizing
Pelletization by layering
Extrusion-
spheronization
Sugar spheres
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (7/38)
DIRECT PALLETIZING
Manufacture of pellets directly from powder.
Round pellets, defined surface
Ideal flow behaviour and
dosability
Narrow particle size distribution
Low abrasion
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (8/38)
Process principle
The impact and acceleration forces that occur in this process result
in the formation of agglomerates, which become rounded out into
uniform and dense pellets.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (9/38)
PALLETIZING BY LAYERING
Layer-by-layer pellet build up around a given
starting core.
Layered pellet Round pellets
Ideal dosability
Low hygroscopicity
Dense, even surface
Narrow grain size distribution
Low wear
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (10/38)
Principle of power layering process
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (11/38)
EQUIPMENT USED FOR THIS PROCESS:
Conventional coating pans.
LIMITATIONS
The degree of mixing is very poor, and the drying process is not
efficient.
If the powder delivery rate is not maintained at pre-determined
equilibrium levels, over-wetting or dust generation may occur.
Toward the end of the layering process, it is likely that fines may
be generated owing to potential inter-particle and wall-to-particle
friction and appear in the final product, thereby lowering the yield.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (12/38)
Principle of solution/suspension layering process
Used when the desired drug loading of the pellets is low.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (13/38)
EQUIPMENT USED FOR THIS PROCESS:
Conventional coating pans
Fluid-bed Centrifugal granulators.
Wurster coaters
An important factor that needs to be considered when
suspensions are used (as compared to solutions) is the particle
size of drug.
Micronized drug particles tend to provide pellets that are smooth
in appearance, a property that is extremely desirable during
subsequent film coating, particulary for controlled-release
applications.
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.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (14/38)
PALLETIZING BY SPHERONIZING
Granulate spheronizing process
EXTRUDERS used for this process are:
Screw-Fed Extruder
Gravity-Fed Extruder
Ram Extruder
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (15/38)
Extruded product spheronizing process
APPLICATIONS OF EXTRUSION SPERONIZATION TECHNIQUE:
High drug loading is possible.
Extended release pellets can be produced.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (16/38)
SUGAR SPHERES
Sugar spheres are produced, preferably using layered
sugar-coating structure.
The ideally rounded spheres are then coated with the
active substance and sustained release additives.
Sugar spheres characteristically consist of sucrose and
corn starch, which are pharmacologically indifferent,
digestible excipients frequently occurring in normal diet.
Sugar spheres mush have adequate mechanical stability
to withstand the loads during subsequent coating,
including contact with solvent.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (17/38)
NEWER TECHNIQUES
Melt spheronization
Spray drying and Spray congealing
Cryopelletization
Freeze pelletization
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (18/38)
MELT SPHERONIZATION
Drug substances and excipients are converted
into a molten or semisolid state and shaped using
appropriate equipment to provide pellets.
Equipments used are: Blenders, extruders, cutters
and spheronizers.
Depending on the characteristics of the
formulation ingredients, pellets that exhibit
immediate or sustained release characteristics
can be manufactured in a single step.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (19/38)
SPRAY DRYING AND SPRAY
CONGEALING
It involves atomization of hot melts, solutions, or
suspensions to generate spherical particles or
pellets.
During spray drying, drug entities in solution or suspension
are sprayed, with our without excipients, into a hot air
stream to generate dry and highly spherical particles.
In spray congealing, a drug substance is allowed to melt,
disperse or dissolve in hot melts of waxes, fatty acids etc.
and sprayed into an air chamber, where the temperature is
below the melting temperature of the formulation
components, to provide spherical congealed pellets under
appropriate processing condition.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (20/38)
CRYOPELLETIZATION
TECHNIQUE
It is a process whereby droplets of a liquid formulation
converted into solid spherical particles or pellets by using
liquid nitrogen as fixing medium.
The procedure permits instantaneous and uniform freezing
of the processed material owing to the rapid heat transfer
that occurs between the droplets and liquid nitrogen. The
pellets are dried in conventional freeze dryers.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (21/38)
The equipment consists of a container equipped with
perforated plates at the bottom. Immediately below the plates
at a predetermined distance is a reservoir of liquid nitrogen. In
which a conveyor belt with transport baffles is immersed.
The conveyor belt has a variable speed and can be adjusted to
provide the residence time required for freezing the pellets.
The perforated plates generate droplets that fall and freeze
instantaneously as they come in contact with the liquid
nitrogen below.
The frozen pellets are transported out of the nitrogen bath into
a storage container at -60°C before drying.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (22/38)
FREEZE-PELLETIZATION
Freeze pelletization is a new and simple technique for producing
spherical pellets for pharmaceutical use.
Molten-solid Carrier(Drug+Excipients) as droplets
Liquid in which the
molten solid is immiscible
Depending upon the
differences in the density,
The solidified droplets may
move downwards or
upwards
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (23/38)
If the density of molten If the density of molten
droplets is higher than droplets is lower than that
that of liquid, then the of liquid, then the
droplets are passed droplets are passed from
from upwards, and downwards, and thus
thus they solidify when they solidify when they
they reach the bottom reach the top of the liquid
of the liquid filled filled vessel.
vessel.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (24/38)
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (25/38)
MicroPxTM Pelletization
technology
The Micro Px™ Technology consists of a continuous fluid bed
process.
After liquid spraying and coating of APIs, generated micropellets are
classified by applying a vertical online air sifting system.
The Micro Px™ Technology process results in manufacturing of high
drug loaded matrix-type micropellets. Drug loadings of produced
pellets can be up to 95%.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (26/38)
Taste Masking:-
Applying Wurster fluid bed technology,
micropellets with a particle size distribution
between 200 to 400 µm were coated with two
functional coatings.
Manufactured Micro Px™ core pellets proved to
be extremely mechanically stable, a prerequisite
for application of subsequent functional coatings
like taste masking, enteric coatings, modified
release coating and similar processes.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (27/38)
ADVANTAGES OF THE MICRO PX™
PELLETIZATION TECHNOLOGY
• small particle size
• spherical pellet shape
• manufactured Micro Px™ pellets reach
very homogeneous and narrow particle
size distribution
• drug loads achievable of up to 95%
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (28/38)
ProCellTM Technology
Process Technology for the manufacture of very high
concentrated spherical particles
Modified fluid bed granulation process
– in particular performed as melt granulation
– no inert starting beads required
– controlled particle movement
Controlled material circulation through special air
flow design
Special processing chamber design, no bottom sieve
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (29/38)
ProCellTM: Spray granulation-Mechanism
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (30/38)
ProCellTM: Product
characteristics
Very high material concentration (up to
100%)
Particle size range from 50 – 1500 µm
High density, low porosity
Particularly suitable for processing of
products with inherent stickiness
Processing of excipients and drug
substances
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (31/38)
Fast Dissolving pellets
Fast Dissolving Pellets are manufactured
using proprietary pelletisation techniques.
Fast Dissolving Pellets consist entirely of
very water soluble and/or swellable
excipients and can be compressed into
orally dispersible tablets (ODTs).
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (32/38)
Characteristics of Fast Dissolving
Pellets
• Narrow particle size distribution, e.g. 100 - 400
µm
• Smooth mouth feel
• Highly water soluble & swellable pharmacopoeial
constituents with low hygroscopic behaviour
• Addition of flavoring agents possible
• Spherical pellets with porous structure; porosity
facilitates disintegration and dissolution
• Mechanically very stable; easy product handling
• Packaging into conventional stick packs feasible
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (33/38)
Cellets
Homogenous distribution of the active agent and the controlled
release are two fundamental advantages of this dosage form.
Due to the uniform concentration of highly active agents more
reliable formulations can be achieved.
As an inert, odorless and tasteless excipient, microcrystalline
cellulose is extremely versatile. Therefore our Cellets® are
made from certified MCC and water only. Allowing combining the
benefits of neutral pellets with the unique properties of cellulose.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (34/38)
Advantages of
Cellets
• Wide range of particle size fractions
• Inert and water insoluble
• Dense, uniform, spherical shaped pellets
• Narrow particle size distribution
• Better for tablet compaction
• No controlled release collapse
• Higher drug load permits smaller capsule size
• Homogenous distribution of API
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (35/38)
Study Questions
WHAT ARE THE CHARACETERISTIC PROPERTIES OF
PELLETS?
STATE THE ADVANTAGES AND DISADVANTAGES OF
PELLETS AS A DOSAGE FORM.
WHAT ARE THE RECENT INNOVATIONS IN
PELLETIZATION TECHNIQUES?
WHAT ARE THE RECENT INNOVATIONS IN PELLETIZED
FORMULATIONS?
CAN INSULIN BE ADMINISTERED BY AN ORAL
FORMULATION? EXPLAIN WITH AN EXAMPLE.
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (36/38)
Reference
s
• The influence of pellet shape and film coating on the filling of pellets into hard
shell capsules., European journal of pharmaceutical and biopharmaceutics, 2006,
53(3) 327-333.
• The effect of shape and porosity on the compression behavior and tablet forming
ability of granular materials formed from microcrystalline cellulose. European
journal of pharmaceutics and biopharmaceutics, 2005, 52, 347-357.
• Influence of process variables on physical properties of pellets using extruder
spheronizer. Drug development industrial pharmacy, 25 (!) , 45-61 (1999).
• Encyclopedia of Pharmaceutical technology, Volume 11, Page no-369.
• [Link]
• Physical characteristics of HPMC and HEC and investigation of their use as
pelletization aids, R. Catlapalli, B.D. Rohera, International Journal of
Pharmaceutics, 161(1998)179-193.
• Eudragit NE40–Drug Mixed Coating System for Controlling Drug Release of Core
Pellets Drug Development And Industrial Pharmacy, Taylor & Francis
Issue: Volume 31 number4-5/2005 Pages: 339 - 347
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (37/38)
