PELLETIZATION
PELLETIZATION
• Pelletization can be defined as an agglomeration (size- enlargement process
that converts fine powders or particles of bulk drugs and excipients into
small, free-flowing, more or lessspherical units, called pellets.
• Pelletization involves the manufacture of agglomerates with a narrow size
range, usually with mean sizefrom 0.5 to 1.5 mm, named “pellets”
• Pellets have free-flowing properties
PELLETIZATION
Advantages
• Uniformity of dose
• Excellent flow properties
• Prevention of dust formation
• Low surface area to volume ratio
• To deliver incompatible bioactive agents
• Improvement of hardness and friability
• Disperse freely throughout the GIT
• Limits localized build up of drug
Disadvantages
• Expensive process and / or requires highly specialized equipment
• Complicated with too many process variables as well as formulation
variables
PELLETIZATION- METHODS
LAYERING TECHNIQUES
• Layeringprocessesare the most well controlled and straight forward
• The layering process comprises the deposition of successive layers of drug
entities from solution, suspension or dry powder on nuclei which may be
crystals or granules of the same material or inert starter seeds.
• Theyare classified into two categories:
• Solution/suspension layering and
• Powder layering
LAYERING TECHNIQUES
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.
LAYERING TECHNIQUES
Powder Layering
LAYERING TECHNIQUES
Powder Layering
• 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.
LAYERING TECHNIQUES
Solution and Suspension Layering
• Solution and suspension layering involve the deposition of
successive layers of solutions and suspensions of drug
substances, respectively, on starter seeds that may be inert
materials or crystals or granules of the same drug.
• In principle, the factors that control coating processes apply
directly to solution or suspension layering.
• During solution or suspension layering, all the components of the
formulation are dissolved or suspended in the application
medium and hence determine the solids contents and the
viscosity of the liquid sprayed.
LAYERING TECHNIQUES
Solution and Suspension Layering
•
LAYERING TECHNIQUES
Solution and Suspension Layering
• As the solution or suspension is sprayed onto the product bed, the droplets
impinge on the starter seeds or cores and spread evenly on the surface, provided
that the drying conditions and fluid dynamics are favorable.
• This is followed by the drying phase which allows dissolved materials
to crystallize and form solid bridges between the core and initial layer of the
drug substance as well as among the successive layers of drug substance.
• The process continues until the desired layers of drug and hence the target
potency of the pellets are achieved.
• The rate of particle growth is rather slow due to the incremental addition of the
dissolved or suspended drug.
LAYERING TECHNIQUES
Fluid bed coating:
Particles are fluidized and the coating fluid sprayed on and dried. Small droplets and a
low viscosity of the spray medium ensure an even product coating.
Different types of fluidized bed processors include top spray coating, bottoms spray
coating (Wurster coating) and tangential spray coating (Rotor pellet coating)
LAYERING TECHNIQUES
LAYERING TECHNIQUES
Process Variables: Product Variables:
1. Fluidization Air Flow 1. Coreparticle
2. Fluidization Air Humidity 2. Particle surface
3. Fluidization Air Temperature 3. Particle size
4. Spray Rate 4. Solution Viscosity and
5. Column Height 5. Solution/Solid Concentration
6. Nozzle and Peristaltic pump
7. AtomizationAir
8. Particle size
EXTRUSION -SPHERONIZATION
Extrusion / Spheronization is a multistage process for obtaining pellets with
uniform sizefrom wet granulates (extrudates).
Themethod involves the following mainsteps:
Dry Mixing of the ingredients, in order to achieve homogenous powder
dispersions
Wet Massing, in which the powders are wet mixed to form a sufficiently
plastic mass
Extrusion Stage, in which the wet mass is shaped into cylindrical segments
with auniform diameter
EXTRUSION -SPHERONIZATION
Spheronization Stage, in which the small cylinders are rolled into solid spheres
(spheroids)
Drying of the spheroids, in order to achieve the desired final moisture
content
Screening (optional), to achieve the desired narrow size distribution
EXTRUSION -SPHERONIZATION
EXTRUSION -SPHERONIZATION
Axial Extruder Radial Extruder
Rotary Cylinder Extruder Rotary Gear Extruder
EXTRUSION -SPHERONIZATION
Spheronization-
• It is also known as ‘Merumerizer’ consists of a static
cylinder and a rotating friction plate where the extrudate is broken up
into smaller cylinders with a length equal to their diameter and these
plastic cylinders are rounded due to frictional forces.
• Two geometric patterns are generally used. It includes a crosshatched
pattern with grooves running at right angle to one another, a radial
pattern with grooves running radially from the center of the disc.
EXTRUSION -SPHERONIZATION
CrYOPELLETIZATION
• Cryopelletization Pellets can be produced by allowing droplets of
liquid formulation such as solution, suspension or emulsion to come
in contact with liquid nitrogen at -160˚C in which liquid nitrogen used
as solidifying medium.
• The procedure permits freezing of the material being processed due
to rapid heat transfer that occurs between the droplets and the liquid
nitrogen for manufacturing a given quantity depends on the solid
content and temperature of solution or suspension being processed.
• The pellets are dried in conventional freeze dryers to remove water or
organic solvents.
SPARY DRYING AND CONGEALING
• Spray-Drying
• During spray drying, a drug solution or suspension is sprayed, with or
without excipients, into a hot-air stream generating dry and highly
spherical particles.
• Though this technique is suitable for development of controlled
release pellets, it is generally employed to improve the dissolution
rates and hence improve the bioavailability of poorly soluble drugs.
• The spray dried powder particles are homogenous, approximately
spherical and nearly uniform in size.
• The design and operation of spray drier can influence a great number
of the characteristics of the final product, such as particle size and size
distribution, bulk density, porosity, moisture content, flowability and
friability.
SPARY DRYING AND CONGEALING
• Spray-Congealing
• It is a technique similar to spray-drying. Spray congealing is a process
in which a drug is allowed to melt, disperse or dissolve in hot melts of
gums, waxes, fattyacids or other melting solids.
• The dispersion is then sprayed into stream of air and other gases with
a temperature below the melting point of formulation components.
• Under appropriate processing conditions, spherical congealed pellets
are obtained.
CHARACTERIZATION
[Link] size distribution
[Link] shape
[Link] morphology (SEM)
[Link] surface area
[Link]
[Link] Time
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[Link]
[Link] strength