Pellet production Technologies Birzeit University - Palestine

1. Pellet Production Technologies
Areej Abu Hanieh
Wafaa Beiruti
Shireen Rawajbeh

2. Introduction: • Pelletization can be defined as an
agglomeration process that
converts fine powders or particles
of bulk drugs and excipients into
small, free flowing, more or less
spherical units, called pellets.
• This technique enables the
formation of spherical beads or
pellets with a mean diameter
usually ranging from 0.5 to 2.0
mm.
• It can be coated and usually used
in controlled release dosage
forms.

3. Pelletization vs. granulation.
• The general terms “granulation” and
“Pelletization” are sometimes used
synonymously and no clear distinction
is made between them.
• generally if agglomerates size
distribution within the range of 0.1 to
2.0 mm and a high porosity (about 20-
50%), this process may be called
granulation.
•But if the agglomerates
have a narrow size
range, usually with mean
size from 0.5 to 2.0mm
and have a low porosity
(about 10%) with free
flowing properties then
it is called Pelletization.

4. 1950 by
pharmaceuticals scientist
Smith kline and French
improve the pellet and
pelletization technique
spheroids particles
tablets , capsules and
suspension

5. Technological Advantages
• Improvement of the uniformity of the content
• Prevention of dust formation.
• Increasing bulk density and decreasing bulk volume.
• The defined shape and weight improves the
appearance of the product.
• Improvement of the handling properties, due to the
free-flowing properties .
• Improvement of the hardness and friability of pellets.
• 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.

6. Therapeutic Advantages
• Pellets can disperse freely throughout an area
of the gastrointestinal tract
• Pellets reduce peak plasma fluctuations and
minimize potential side effects
• Avoiding the irritant effect of some drugs on
the gastric mucosa
• Modified-release multiparticulate delivery
systems are less susceptible to dose dumping
than single-unit dosage forms

7. • Often pellets can not be pressed into tablets
because they are too rigid. In that case, pellets
have to be encapsulated into capsules.
• The production of pellets is often an expensive
process and / or requires highly specialized
equipment.
• The control of the production process is difficult
(e.g. the amount of water to be added is critical
for the quality of the pellets and overwetting can
occur very easily).
Disadvantages

8. Pelletization techniques:
 Extrusion/ Spheronisation.
 Dry powder layering.
 Spray-congealing.
 Fluid-bed granulation.
 Solution and suspension
layering.
 Spray-drying.

9. Extrusion-Spheronization:-
• Extrusion is necessary first step in the extrusion-spheronization process.
• The size of the sphere are determined by the diameter of the extrudate used.
The extrusion-spheronization process can be broken down into following steps:-

11. Screw extruder:-
• Commonly used in industrial application.
• Higher pressure and heat can degrade
pharmaceutical products.

12. Screen or basket
extruder:
- Lower
density
extrudate.
- Relatively
high
throughput.
Gear extruder:
- produces
relatively
high density.
- Gears are
robust and
last longer
Gear Extruder
Basket Extruder

13. Spheronization
• spheronization is a process of forming a spherical particles
from different rod shapes , by extrusion , that has a diameter
ranging from 0.5 to 1 mm .

14. • The size of the spheres are determined by the diameter of the
extrudate used for the spheronization process. For example,
in order to obtain spheres with a diameter of 1 mm, a 1 mm
screen is used on the extruder.

15. Spheronization machine design
• In principle the basic machine consists of a rotating friction disk, designed to increase
friction with the product, which spins at high speed at the bottom of a cylindrical bowl.
The spinning friction disc has a carefully designed groove pattern on the processing
surface. This is most often crosshatched, but several sizes and other types are
available.

16. Spheronization mechanism of action
• as the machine rotate , rods move in rotationary movement or woven rope
movement , and the most important point that rods should not be friable but
it should have a plastic properties to have the ability to spheronized.
Video for
Spheronization

17. Key Spheronization Factors:
• Disc speed and load
• Disc groove geometry
• Disc diameter and speed
• Retention time
• Product paramaters
• Other factors

18. Disc Speed
There is an optimum disc speed and load for each disc diameter:
- Momentum too low:
Extrudate not densified
sufficiently.
No spheres formed.
Granules fracturing.
- Momentum too high (from under
loading or disc speed too high):
Too much force on the
granules.
Compression of particles
within the granules.
Minimum porosity.

19. Disc Groove Geometry:
• Both radial and cross hatched will work effectively.
• Radial disc had gentler and more controlled action.
• Radial not suitable for large diameter discs.
Cross Hatched Disk Radial Disk

20. Retention time:
• Typical retention time to obtain spheres range
from 2 to 6 minutes.
• The edges of cylindrical granules are the most
fragile part and they will generate dust during
handling .
• Spheronization with short retention time can
help to reduce dust significantly.

21. Table summarizing the different types of caleva
spheronizers for pharmaceutical production and
development :
Equipment Description Main use
Micro spheronizer A Bench Top Laboratory
Unit
Laboratory:small quantity
Spheronizer-120 Bench top Laboratory/experimental
Spheronizer-250 Lab scale bench top Low cost high output
Spheronizer-380 A Production or Pilot Plant
Spheronizer
Quality spheroids output
Spheronizer-500 A Production or Pilot Plant
Spheronizer
Quality spheroids output

22. Main stages in the fluid bed
Drying:

23. Granulation / agglomeration:

24. • Powder coating / particle coating:

25. Pelletizing

26. Types of fluid bed technologies
Top spray Bottom spray Tangential spray

27. Tangential Spray(Rotor Process)
Parameters:
•Liquid addition rate
•Inlet air temp.
•Humidity
•Atomization air pressure
•Binder type and
concentration
•Disk speed
•Disk gap

28. ROTOGRANULATION
Rotogranulation is one of the most recent methods for the
production of spheroids. The single-unit spheronizing system
can be described using terms like centrifugal granulator, rotary
fluidized-bed granulator, rotary fluid bed, rotary processor or
rotor granulator :
1)The preblending of the formulation powder, including the
active ingredients, fillers, disintegrants, in a flow of air.
2)The granulation of the mixture by spraying a suitable
liquid binder onto the fl uidized (suspended) powder bed.
3) The drying of the granulated product to the desired
moisture content.

29. • During processing, three mechanical forces cause particle
movement, mixing, and granulating.
• First, the spinning of the disk generates a centrifugal force.
• Second, a lifting force is generated by the hot air passes
through the adjustable disk gap.
• Third, gravitational force causes material to fall down onto
the disk.
• These forces provide good mixing and result in granules,
drying, coating with good content uniformity.

30. During spraying-drying, a drug is solution or
suspension is sprayed, with or without
excipients, into a hot-air stream, generating
dry and highly spherical particles.
Spray-drying
Spray-drying represents another process
based on globulation.

32. Inlet air temperature: 180-
250 Co .
Outlet air temperature:
80-115Co ..
Inlet moisture content:
75-85%.
outlet moisture content:
3-3.5%.
Operating
conditions:Spray rate:
2290kghr
Air flow
rate:
31500kg
hr.

33. Advantages:
• This technique is suitable for
development of controlled-released
pellets.
• It is generally employed to improve
dissolution rates and bioavailability of
poor soluble drugs.
• This method is applied for heat
sensitive pharmaceuticals: amino acids,
antibiotics, ascorbic acid, liver
extracts, pepsin and similar enzymes,
protein hydrosylate and thiamine.
• Particle size and size distribution, bulk
density, porosity, moisture content,
flowability and friability can be easily
controlled by the design and operation
of the spray drier.
The spray-dried
powder particles are
homogenous,
approximately
spherical, nearly
uniform in size.

34. Spray-congealing:
Spray-congealing is similar to
spray-drying, it is also called
spray-chilling.
In spray-congealing the drug is
allowed to melt, disperse or dissolve
in hot melts of gums, waxes, fatty
acids, or other melting solids.
The dispersion is them sprayed into a
stream of air and other gases with a
temperature below the melting point
of the formulation components,
under appropriate processing
conditions, spherical congealed
pellets are obtained.