Pharmaceutical process of spheronization and marumerisers

1. SPHERONIZERS AND MARUMERISERS
BY SHREYAS REDDY

2. GRANULATION
 Granulation is the process in which primary powder particles are made to
adhere to form larger, multi particle aggregates called granules.
 Granulation is mainly used to improve the flow properties of powders and
compressibility of powders, and to prevent segregation of blend components.
 Granulation method can be broadly classified in to 3 types
• Wet granulation
• Dry granulation
• Granulation incorporating bound moisture

3. REASONS FOR GRANULATION
 To improve the flow properties of the mix.
 To prevent the segregation of the constituents of the powder mix.
 Granules being denser than the powder mix, occupies less volume per unit
weight. They are more convenient for storage and shipment.
 Materials which are slightly hygroscopic may adhere and form a cake if
stored as powder.

4. IDEAL CHARACTERISTICS OF GRANULES
 Spherical in shape
 Smaller particle size distribution with sufficient fines to fill void spaces
between granules.
 Adequate moisture content (1-2%)
 Good compressibility
 Sufficient hardness

5. EXTRUSION
 Extrusion is a necessary first step in the extrusion spheronisation process.
 It is the process of forming a raw material into a product of uniform shape
and density by forming it through an orifice or die under controlled
conditions.
 Extrudate must have enough plasticity to deform, but extrudate particles do
not adhere to other particles when collected.

6. The primary extrusion process variables are:
• The feed rate of the wet mass
• The diameter of the die
• The length of the die
• The water content of the wet mass

7. BASED ON THEIR FEED MECHANISM
EXTRUDERS DIVIDED INTO..

8.  Screw feed extruder:
 Commonly used in industrial application.
 High pressure and heat can degrade pharmaceutical product
 Screen or basket extruder:
 Lower density extrudate.
 Relatively high through put.
 Gear extruder:
 Produces relatively high density.
 Gears are robust and long lasting.
 The mini screw extruder:
 For small quantity of material
 Smallest batch size can be extruded is about 5g.
 Material loaded into it manually
 Die hole size is 0.7mm to 2 mm
 Minimum wastage of valuable product
 Can be quickly dismantled for easy cleaning

9. SPHERONISATION
• Spheronization is a rapid or flexible process where
extrudates (the output from an extruder) are shaped
into small rounded or spherical granules. In practice
these usually vary in size from 0.4 to about 3.0 mm. The
use of these spheroids can be relevant for a wide variety
of industries

10. ADVANTAGES OF SPHERONIZATION
Optimum flow and handling characteristics: The flow characteristics of spheres makes them suitable
for transportation by most systems found in the pharmaceutical industry, including vacuum transfer.
More reproducible packing into small containers: The packing into small containers, such as hard
gelatine capsules, or larger packages is much more convenient than other drug form such as powders
or granules. Eliminate quality problems with variable dosage due to packing problems with powder.
Minimum surface area to volume ratio: Spheres provide the lowest surface area to volume ratio and
thus pharmaceutical compounds can be coated with minimum of coating material. Important for
effective release of some drugs.
Optimum shape for coating and for controlled release: Coating can provide controlled, targeted
release at different location within the body. Spheres are dense material that can easily be coated
within a minimum of coating material.
Easy mixing of non-compatible products: spherical particles are easily mixed.
Elimination of dust: Contamination is reduced. The amount of fines and dust will be reduced during
transport and handling.
Improved hardness and friability: Spheronization increases the hardness and reduces friability of

11. SPHERONISATION PROCESS
 Dry mixing of ingredients- to achieve a homogenous powder
dispersion.
 Wet massing – to produce a sufficiently plastic wet mass.
 Extrusion – to form rod shaped particles of uniform diameter.
 Spheronisation- to round of these rods into spherical particles.
 Drying – to achieve the desired final moisture content.
Screening- to achieve the desired narrow size distribution

12. EXTRUSION/ SPHERONISATION PROCESS
FLOW CHART

13. SPHERONIZER
•Construction

14. SPHERONIZER OR MARUMIZER
 A Spheronizer known as Marumerizer consists of a static cylinder or stator and a rotating friction plate or
disk at the base.
 The stator can be jacketed for temperature control.
 The friction plate, a rotating disk which has a grooved surface, is the most important part of the equipment
that initiates the Spheronization process. A standard friction plate has a cross-hatch pattern, where the
grooves intersect at a 90° angle.
 The groove width is selected based on the desired pellet diameter. Usually groove diameter 1.5-2 times the
target pellet diameter is used.
 The diameter of the friction plate is approximately 20 cm for laboratory-scale equipment or up to 1m for
production-scale units.

15. PRINCIPLE AND WORKING OF SPHERONIZER
 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.
 The ongoing action of particles colliding with the wall and being thrown back to the inside
of the plate creates a "rope-like" movement of product along the bowl wall.
 When the particles have obtained the desired spherical shape, the discharge valve of the
chamber is opened and the granules are discharged by the centrifugal force.
 The rounding of the extrudate into spheres is dependent on frictional forces generated by
the particle-particle collision particle–equipment collisions.

16. PRINCIPLE & WORKING
 The bottom disc has a grooved surface to increase these forces. Two geometric patterns are generally used.
• 1. A cross –hatched pattern with grooves running at right angles to one another.
• 2. A radial pattern with grooves running radially from the centre of the disc.

17. THE TRANSITION
• The transition from rods to spheres during spheronization occurs in
various stages:
• Cylinder----cylinder with rounded ends ----dumbbell---- eclipsed---
spheres

18. KEY SPHERONIZATION FACTORS
 Disc speed
 Spheronizer drum charge volume
 Disc groove geometry
 Disc diameter and speed
 Retention time

19. FACTORS
1. Disc Speed:-
 There is an optimum disc speed and load for each disc diameter
 If Momentum too low:
• Extrudate not densified sufficiently
• No spheres formed
 If 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
• Granules fracturing
2. The Spheronizer Drum Charge Volume: The optimum charging volume depends upon the machine size and the
product characteristics. A typical charge volume for a machine with a 380 mm diameter disc is about disc is 4 liters,
depending on the density of the material. Increasing the batch size increases the hardness of the spheres and smoothens
the granule surface.

20. FACTORS
3. Disc Groove Geometry:The most common groove pattern used for spheronizer discs is
the square cross-hatched square design, where the processing surface is covered with a
grid of truncated pyramids. Generally, extrudates up to 0.8 mm in diameter are normally
processed on a 2 mm pitch plate with a 3 mm pitch plate is used for extrudates up to 3 mm
in diameter. Discs with a radial design are used for gentler action on the material being
spheronized.
4. Disc Diameter: Peripheral speed (related to disk diameter) was a major influence on the
Spheronization process with constant peripheral speed: Loads from 0.5 to 25 kg can be
compared.
5. Retention time: Typical Spheronization retention time necessary to obtain spheres is from
3 to 8 minutes. Spheronisation with a short retention time can help to reduce the amount of
dust significantly

21. ADVANTAGES AND DISADVANTAGES
• Advantages:-
 Easy to coat.
 Separation of incompatible drugs.
 Ability to mix pellets with different release rates.
 Reduced risk+ of dose dumping.
 Reduced risk of local irritation in the gastro-intestinal tract.
 Less variable bio-availability. Particles of 1mm or less behave more like liquids in terms of gastric emptying
 Even distribution over the gastro-intestinal tract.
• Disadvantages:-
 Equipment is expensive.

22. PHARMACEUTICAL APPLICATIONS FOR EXTRUDERS
AND SPHERONIZER
 Controlled release pellets for encapsulation
 Delayed release enteric coated pellets
 Sustained release pellets
 Multi-particulate systems
 Multi-unit erosion matrix pellets
 Pellets for special tableting applications
Equipment Description Mainuse
Microspheronizer --------- Laboratory:smallquantity
Spheronizer-120 Benchtop Laboratory/experimental
Spheronizer-250 Labscalebenchtop Lowcosthighoutput
Spheronizer-380 ------ Qualityspheroidsoutput
Spheronizer-500 ------- Qualityspheroidsoutput

23. MACHINE PARAMETERS
The basic machine consist of a round disc with rotating drive shaft, spinning at
the bottom of a cylindrical bowl. This is most often cross hatched, several sizes
available. These discs are designed to increase the friction with the product.
• Friction plate pattern
• Friction plate speed
• Retention time
• The charge volume

24. MACHINE PARAMETERS
1.Friction plate pattern:-
• The most common groove pattern used for spheroniser discs is the “waffle-iron” or cross hatch design ,where the friction plate is like a
chessboard of chopped off pyramids.
• Discs with a radial design are also used.
2.Friction plate speed:-
• Thetypicalrotationspeedofa700mmdiameterdiscranges from 400 to 500 rpm.
• The optimum speed depends on the characteristics of the product and the particle size.
3.Retention time:-
• Typical retention time to obtain spheres range from 2 to 6minutes.
• 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.
4.The charge volume:-
• The optimum level depends upon the machine size and the product characteristics
• Increasing the load per batch increases the hardness of the spheres and smooths the granule surface.

25. FEATURES AND BENEFITS
• Spheronization improves your product's performance by:
 Producing a smooth particle surface suitable for thin layer coating.
 Forming granules with a specific bio-consumable shape.
 Conditioning particles to prevent generation of dust and fines from usage or
shipping.
 Increasing flow ability by elimination of sticking or bridging points.
 Increasing the apparent bulk density up to 25% compared to extruded material.

26. MARUMERIZER
 Marumerizer is a production scale spheronizer which converts the wet pellets into
spheres.
 Marumerization, is a rapid and flexible process where pharmaceutical products are
made into small spheres, or spheroids of diameter ranging from about 0.8mm to1.5mm.
 Operation: The feed material to the spheronizer can be extruded particles or moist
granules from a mixer/granulator. Since an extruded particle has at least two dimensions
already defined, a narrow final particle size distribution is possible.
 Particles are fed onto the spinning friction plate, which throws them against the inside
wall of the cylinder. Extruded particles are quickly broken into segments approximately
one diameter long.

27. HOW IT WORKS
 The Marumerizer spheronizer is comprised of three main components: a vertical cylinder with discharge port, a
circular "friction" plate and a variable speed drive train which turns the plate.
 The feed material to the spheronizer can be extruded particles or moist granules from a mixer/granulator. Since an
extruded particle has at least two dimensions already defined, a narrow final particle size distribution is possible.
 Particles are fed onto the spinning friction plate, which throws them against the inside wall of the cylinder.
 Extruded particles are quickly broken into segments approximately one diameter long.
 Centrifugal and gravitational forces create a mechanically fluidized ring of particles.
 Collisions with the wall, friction plate and other particles result in the plastic deformation of each granule, quickly
creating a spherical shape.
 The desired shape for a specific application is time and formulation dependent and is achieved, predictably and
repeatedly, in a brief period called the "Spheronization time".

28. MODELS
Model M-380 M-500 M -700 M -900 M -700(T) M -900(T)
Batch
cap./kgs.
0.5-3.2 3-10 5-20 15-50 10-40 30-100
M- Marumerizer

29. DIFFERENT TYPES OF GRANULATORS
LOW SHEAR MIXER

30. HIGH SHEAR MIXER

31. ROTOR GRANULATOR

32. FLUIDIZED BED

33. ADVANCED TECHNIQUES
1) Freeze Granulation Technology
2) Steam Granulation Technology (SGT)
3) Thermoplastic Granulation Technology (TGT)
4) Moist Granulation Technique (MGT)
5) Thermal Adhesion Granulation Process (TAGP)
6) Pneumatic Dry Granulation Technology (PDGT)
7) TOPO Technology
8) Continuous Flow Technology (CFT)
9) Foam Granulation Technology (FGT)
10)Pneumatic Dry Granulation Technology (PDGT)

34. MOISTURE ACTIVATED DRY
GRANULATION (MAGD)

35. FOAM GRANULATION TECHNOLOGY (FGT)

36. STEAM GRANULATION TECHNOLOGY (SGT)

37. FREEZE GRANULATION TECHNOLOGY

38. THERMOPLASTIC GRANULATION TECHNOLOGY (TGT )