Chapter on Pellets

Chapter on Pellets

1. PELLETS
AND INNOVATIONS IN
PELLETS
By:RajeshL. Dumpala
(B.Pharm, M. Pharm.) PhD. ( Pursuing)
Research Scientist,
Alembic Research Centre. Vadodara
E.Mail:[email protected]

2. LIST OF CONTENT
•Definition
•Characteristics properties of pellets
•Advantages and disadvantages of pellets
•Pelletization process
•Newer techniques
•Recent innovation

3. What is
pellet?
Pellets are defined as small, sphericalparticulates
produced by theagglomerationof 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.

4. 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.
CHARACTERISTICS PROPERTIES OF
PELLETS

5. They can be dispensed as such, filled into a capsuleas well as
can be compressed into a tablet.
They can be also used to dispenseincompatible bioactive
agentstogether into a single formulation.
They can be divided into desired dose strengthswithout
formulation or process changes.
Different release profilesin a single formulation can be met.
Release of drugs at different sitesin the GIT.
Upon oral administration, they maximize absorptionas they
freely disperse in GIT.
ADVANTAGES OF PELLETS

6. DISADVANTAGES OF PELLETS
If the pellets are volume filled, for example in capsules, it
may lead to the problems of content uniformityand
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 roughnessof 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 chargesdevelop that lead to blocking during
the filling process.

7. PELLETIZATION PROCESSES
Direct palletizing
Pelletization by layering
Extrusion-spheronization
Sugar spheres

8. Manufacture of pellets directly from powder.
DIRECT PALLETIZING
Round pellets, defined surface
Ideal flow behaviour and dosability
Narrow particle size distribution
Low abrasion

9. Process principle
The impact and acceleration forcesthat occur in this process result
in the formation ofagglomerates, which become rounded out into
uniformand dense pellets.

10. 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

11. Principle of power layering process

12. EQUIPMENT USED FOR THIS PROCESS:
Conventional coating pans.
LIMITATIONS
The degree of mixingis very poor, and the dryingprocess is not
efficient.
If the powder delivery rate is not maintained at pre-determined
equilibrium levels, over-wetting or dust generationmay occur.
Toward the end of the layering process, it is likely that finesmay be
generated owing to potential inter-particleand wall-to-particle friction
and appear in the final product, thereby lowering the yield.

13. Principle of solution/suspension layering process
Used when the desired drug loading of the pellets is low.

14. 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 sizeof drug.
Micronized drug particlestend to provide pellets that aresmoothin
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 islarge, the amount
of binderrequired to immobilize the particles onto the cores will be
highand consequently, pellets of low potencyare produced. The
morphology of the finished pellets also tends to be rough and may
adversely affect the coating processand the coated product.

15. PALLETIZING BY SPHERONIZING
Granulate spheronizing process
EXTRUDERS used for this process are:
Screw-Fed Extruder
Gravity-Fed Extruder
Ram Extruder

16. Extruded product spheronizing process
APPLICATIONS OF EXTRUSION SPERONIZATION TECHNIQUE:
High drug loading is possible.
Extended release pellets can be produced.

17. Sugar spheres are produced, preferably using layered sugar-
coating structure.
The ideally rounded spheresare then coated with the active
substance and sustained release additives.
Sugar spheres characteristically consist of sucroseand corn
starch, which are pharmacologically indifferent, digestible
excipients frequently occurring in normal diet.
Sugar spheres mush have adequate mechanical stabilityto
withstand the loads during subsequent coating, including
contact with solvent.
SUGAR SPHERES

18. NEWER TECHNIQUES
Melt spheronization
Spray drying and Spray congealing
Cryopelletization
Freeze pelletization

19. Drug substances and excipients are converted into a
molten or semisolid stateand 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 releasecharacteristics can be
manufactured in a single step.
MELT SPHERONIZATION

20. SPRAY DRYING AND SPRAY CONGEALING
It involves atomization of hot melts, solutions, or
suspensionsto 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.

21. 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 permitsinstantaneousand uniform freezingof
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.
CRYOPELLETIZATION TECHNIQUE

22. 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 beltwith transport baffles is immersed.
The conveyor belt has a variable speedand 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.

23. FREEZE-PELLETIZATION
Freezepelletizationisanewandsimpletechniqueforproducing
sphericalpelletsforpharmaceuticaluse.
Molten-solidCarrier(Drug+Excipients)asdroplets
Liquid in which the
molten solid is immiscible
Depending upon the
differences in the density,
The solidified droplets may
move downwardsor
upwards

24. Ifthedensityofmolten
dropletsishigherthan
thatofliquid,thenthe
dropletsarepassed
fromupwards,andthus
theysolidifywhenthey
reachthebottomofthe
liquidfilledvessel.
Ifthedensityofmolten
dropletsislowerthanthat
ofliquid,thenthedroplets
are passed from
downwards,andthusthey
solidifywhentheyreach
thetopoftheliquidfilled
vessel.

26. 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%.
MicroPx
TM
Pelletization technology

27. Taste Masking:-
Applying Wurster fluid bed technology, micropellets
with a particle size distribution between 200 to 400
µmwere 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.

28. •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%
ADVANTAGES OF THE MICRO PX™
PELLETIZATION TECHNOLOGY

29. 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
ProCell
TM
Technology

30. ProCellTM: Spray granulation-Mechanism

31. 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
ProCellTM: Product characteristics

32. 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).
Fast Dissolving pellets

33. •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
Characteristics of Fast Dissolving Pellets

34. Homogenous distributionof the active agent and the controlled
releaseare 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
celluloseis 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.
Cellets

35. •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
Advantages of Cellets

36. Study Questions
WHAT ARETHE CHARACETERISTIC PROPERTIES OF
PELLETS?
STATE THEADVANTAGES AND DISADVANTAGES OF
PELLETSASADOSAGEFORM.
WHATARETHERECENTINNOVATIONS INPELLETIZATION
TECHNIQUES?
WHAT ARETHERECENTINNOVATIONS INPELLETIZED
FORMULATIONS?
CAN INSULIN BEADMINISTERED BYAN ORAL
FORMULATION? EXPLAINWITHANEXAMPLE.

37. • 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.
• http://www.andrx.com
• 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
References
VIVEK PATEL PAPER 421,PELLETS,LMCP’07-08 (37/38)