PELLETIZATION TECHNIQUES
WHAT ARE PELLETS?
In the pharmaceutical industry, pellets can be defined as small, free-flowing, spherical
particulates manufactured by the agglomeration of fine powders or granules of drug
substances and excipients using appropriate processing equipment.
Advantages of Pellets:
✓ Excellent Stability
✓ Dust free
✓ Round pellets
✓ Good flow behavior
✓ Easy to dose
✓ Compact structure
✓ Very Low hygroscopicity
✓ High bulk density
✓ Dense, uniform surface
✓ High active ingredient content possible
✓ Optimum starting shape for subsequent coating
✓ Controlled-release applications
✓ Drug absorption
TECHNIQUES:
Powder layering
Solution/Suspension layering
Extrusion–Spheronization
Spherical agglomeration or balling
Spray congealing/ drying
Cryopelletization and Melt Spheronization.
POWDER LAYERING
Powder layering involves the deposition of successive layers of dry powder of drug or
excipients or both on preformed nuclei or cores with the help of a binding liquid. Powder
layering involves the simultaneous application of the binding liquid and dry powder. The first
equipment used to manufacture pellets on a commercial scale was the conventional coating
pan, but it has significant limitations as pelletization equipment. Mixing is a function of the
Pan shape, the Tilt angle, the Baffle arrangement, and the Rotational speed of the pan itself.
Throughout the process, it is extremely important to deliver the powder accurately at a
predetermined rate and in a manner that maintains equilibrium between the binder liquid
application rate and the powder delivery rate. If the powder delivery rate is not maintained at
predetermined equilibrium levels, over wetting or dust generation may occur, and neither the
quality nor the yield of the product can be maximized. In an ideal process, no agglomeration
occurs, and the particle population at the end of the process remains the same as that of the
starter seeds or cores, with the only difference being an increase in the size of the pellets and
thus in the total mass in the pan.
Other equipments used for powder layering process are: Tangential Spray granulator
Centrifugal Fluid Bed granulator
SOLUTION/SUSPENSION LAYERING
A starting grain or a pellet can be presented as the starting material. The pellet is built up to
the required grain size by adding the layering substance one layer at a time. Powder and
binders, suspensions or solutions make suitable layering substances. The layers are densely
applied due to the movement of the pellets. Thick layers can be applied to the starting grains,
which, in the case of layers containing active ingredients.
As the particles continue travelling upwards, they dry and fall outside the Wurster tube back
towards the base plate. They are guided from the outside back to the inside of the tube where
they are once again accelerated by the spray. This produces an extremely even film. Particles
of different sizes are evenly coated.
EXTRUSION-SPHERONIZATION
Extrusion–Spheronization is a multistep process involving dry mixing, wet granulation,
extrusion, Spheronization, drying and screening.
SPHERICAL AGGLOMERATION
Spherical agglomeration, or balling, is a pelletization process in which powders, on addition
of an appropriate quantity of liquid; when subjected to high temperatures, are converted to
spherical particles by a continuous rolling or tumbling action. Spherical agglomeration can be
divided into two categories — Liquid-induced Melt-induced agglomerations.
Liquid-induced agglomeration: During liquid-induced agglomeration, liquid is added to the
powder before or during the agitation step. As powders come in contact with a liquid phase,
they form agglomerates or nuclei. The solid bridges, which are derived from the hardening
binder or any other dissolved material within the liquid phase. The nuclei formed collide with
other adjacent nuclei & coalesce to form larger nuclei or pellets. At this point, coalescence is
replaced by layering, whereby small particles adhere on much larger particles and increase
the size of the latter until pelletization is completed.
Melt-induced agglomeration: Melt-induced agglomeration processes are similar to liquid-
induced processes except that the binding material is a melt. Therefore, the pellets are formed
with the help of congealed material without having to go through the formation of solvent-
based liquid bridges If the surface moisture is not optimum, some particles may undergo
nucleation and coalescence at different rates and form different sizes of nuclei admixed with
the larger pellets. As a result, spherical agglomeration tends to produce pellets with a wide
particle size distribution.
SPRAY DRYING AND SPRAY CONGEALING, known as globulation processes, involve
atomization of hot melts, solutions, or suspensions to generate spherical particles or pellets.
The droplet size in both processes is kept small to maximize the rate of evaporation or
congealing, and consequently the particle size of the pellets produced is usually very small.
Spray Drying: This drying process continues through a series of stages whereby the viscosity
of the droplets constantly increases until finally almost the entire application medium is
driven off and solid particles are formed.
Spray Congealing: This process consists of suspending the particles in a molten coating
material and pumping the resultant slurry into a spray dryer in which cold air is circulated.
The slurry droplets congeal on contact with the air. The coating agents normally employed
are low melting materials such as waxes. The congealing process require higher ratio of
coating agents to active material than does the spray drying, because only the molten coating
agent constitutes the liquid phase.
MELT SPHERONIZATION is a process whereby a drug substance and excipients are
converted into a molten or semi molten state and subsequently shaped using appropriate
equipment to provide solid spheres or pellets. The drug substance is first blended with the
appropriate pharmaceutical excipients, such as polymers and waxes, and extruded at a
predetermined temperature. The extrusion temperature must be high enough to melt at least
one or more of the formulation components. The extrudate is cut into uniform cylindrical
segments with a cutter. The segments are spheronized in a jacketed Spheronizer to generate
uniformly sized pellets.
CRYOPELLETIZATION
Cryopelletization is a process whereby droplets of a liquid formulation are converted into
solid spherical particles or pellets by using liquid nitrogen as the fixing medium. The
technology, which was initially developed for lyophilization of viscous bacterial suspensions,
can be used to produce drug-loaded pellets in liquid nitrogen at -160 ⁰C. 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 amount of liquid nitrogen
required for manufacturing a given quantity depends on the solids content and temperature of
the solution or suspension being processed.