$ CONTENTS $ #Introduction #Objective of granulation #Essential properties of granules #Mechanism of bond formation #Mechanism of granule formation #Method of granulation #Modern equipments in granulation technology

1. Granulation and
Modern Equipments
Presented By
Sarang Vilas Dalvi
Goverment College of Pharmacy , Amravati. 444604.
2017-2018

2. • Introduction
• Objective of granulation
• Essential properties of granules
• Mechanism of bond formation
• Mechanism of granule formation
• Method of granulation
• Modern equipments in granulation technology
CONTENTS

3. Granulation Process
Introduction:
• Granulation is the process of collecting particles
together by creating bonds between them. Bonds are
formed by compression or by using a binding agent.
•Pharmaceuticals granules typically have a size range
between 0.2-4.0 mm, depending on the subsequent
use of the granules.
•Pharmaceutical ‘‘granulated’’ material is derived from
the Latin word ‘‘granulatum,’’ meaning grained.

4. Objective of Granulation
• To improve the compaction characteristic of the
mix.
• To prevent segregation of the constituents of the
powder mix.
• To improve the flow properties of the mix.
• To produce uniform mixtures.
• To eliminate poor content uniformity.
• To produce dust free formulation.
• To capture and fuse small quantities of active
material.
• To control density.
• The objective of granulation process is to combine

5. Granules should have
• Spherical shape
• Smaller size particle size distribution with
sufficient fines to fill void spaces between
granules.
• Optimum moisture content (1-2 %)
• Good flow
• Good compressibility
• Sufficient hardness
Essential properties of granules

6. There are FIVE primary bonding mechanisms:
 Adhesion and cohesion forces in the immobile
liquid films between individual primary powder
particles.
 Interfacial forces in mobile liquid films within
the granules.
 The formation of solid bridges after solvent
evaporation.
 Attractive forces between solid particles.
 Mechanical interlocking.
Mechanisms of bond formation

7. • Addition of binder solution, increase in contact area
of particles. The bond strength increases due to
van der waal forces. On drying immobile film form.
In dry granulation, the
pressures used will
increase the contact
area between the
adsorption layers and
decrease the inter-particulate distance, and this will
contribute to the final granule strength.
1.Adhesion and cohesion forces in immobile
films

8. There are three states of water distribution between
particles as shown below:
1. Pendular State 2. Funicular State
2. Capillary State 3. Droplet State
2.Interfacial forces in mobile liquid films

9. These can be formed by:
• partial melting
• hardening binders
• Crystallization of dissolved substances.
3. Formation of Solid bridge After
Evaporation:

10. Partial melting:
• At high pressure low melting point substances melts
on removing pressure they crystalizes. Eg. Stearic acid.
Hardening binders:
• when an binder is included in the granulating solvent, the
liquid will form liquid bridges, and the binder will harden or
crystallize on drying to form solid bridges to bind the
particles. Eg. Carboxymethylcellulose, starch.
Crystallization of dissolved substances:
• The solvent used to mass the powder during wet granulation
may partially dissolve one of the powdered ingredients. When
the granules are dried, crystallization of this material will take
place. Eg. Lactose.

11. Two types of attractive force:
• Electrostatic forces: Electrostatic
forces may be important in causing powder
cohesion and the initial formation of
agglomerates e.g. during mixing.
• Van der Waals forces:
are about four orders of magnitude greater than
electrostatic and add to the strength of granules
produced by dry granulation.
4.Attractive forces between solid particles

12. • Adhesive penetrates into the pores, holes and
crevices and other irregularities of the adhered
surface of a substrate.
• locks mechanically to the substrate.
5. Mechanical Interlocking:

13. a) Nucleation: Granulation starts with particle-particle
contact and adhesion due to liquid bridges.
b) Transition: Nuclei can grow in two possible ways:
• single particles can be added to the nuclei
• two or more nuclei may combine.
c) Ball Growth: If
agitation is continued,
granule coalescence will
continue.
Mechanisms of Granule Formation

14. Mainly two types of granulation
• Wet granulation
addition of a liquid solution (with or without binder)
• Dry granulation
without using a liquid solution
Granulation methods

15. WET GRANULATION
1. Milling and Weighing of drug and excipients
2. Mixing
3. Wet massing
4. Wet screening (Granulation)
5. Drying
6. Dry screening
7. Lubrication of granules

16. DRY GRANULATION
1. Milling and Weighing of drug and excipients
2. Screening
3. Blending
4. Slugging
5. Granulation
6. Lubrication
7. Compaction

17. • Those materials which do not compress well after
wet granulation.
• Those material which are sensitive to moisture. Due
to hydrolysis of API may occur.
• Material which are heat sensitive.
• Less time consuming.
Slug: Slug may be described as poorly formed tablet
or compacted mass of powdered material.
Advantages of dry granulation

18. Sr.
no.
Wet granulation Dry granulation
1 Use of solvent No use of solvent
2 Use of wet binder Use of dry binder
3 Formation of wet mass is
intermediate process.
Formation of slug is intermediate
process.
4 Temperature and heat are required
for drying of granules.
No heat and temperature are
required for drying of granules.
5 Applicable for moisture resistant
drugs. Eg ester and amide type of
drugs.
Use for moisture sensitive drugs,
which prevent hydrolysis of drugs.
6 Not applicable for thermosensitive
material. Eg vitamins and protein
tablets.
Applicable for thermosensitive
materials.

19. 1. Oscillating granulator
2. Gral mixer processer
3. Fluidized Bed Granulator
4. Double cone granulator
5. Diosna mixer granulator
6. Day Nauta mixer processer
7. Topo vacuum pressure
8. Chilsonator (Roller compacter)
MODERN EQUIPMENTS USED IN
GRANULATION TECHNOLOGY

20. • The moist mass has been transferred to a
granulator, as oscillating granulator. The rotor bars
of the granulator oscillate and force the moist mass
through the sieve screen, the size of which
determines the granule size.
• The mass should be sufficiently
moist to form discrete granules when
sieved. If excess liquid is added,
string (filament) of material will be
formed and if the mix is too dry the
mass will be sieved as powder and
granules will not be formed.
1. Oscillating granulator

21. • This is modification of industrial planetary mixer.
• The principle is based upon the planetary mixer.
• It contain two mixing devices. Larger three blade
shaft provide mixing motion on powder.
• Smaller chopper blade used to cut the wet mass into
granules.
• The main mixing blade rotates at 450-600 rpm in 10
L model.
• In all models the high speed
chopper blade rotates at
1500-3000 rpm.
2. Gral mixer processer

22. • The powder particles are fluidized in a stream of air.
• Granulation fluid is pumped from a reservoir and
sprayed from a nozzle on to the bed of powders.
• Heated and filtered air is blown through the bed of
unmixed powders to fluidize the particles admix the
powders.
• The fluid causes the
primary powder
particles to adhere
when the droplets
and powders collide.
3. Fluidized Bed Granulator

23. • Sufficient liquid is sprayed to produce granules of the
required size, at which point the spray is turned off but
the fluidizing air continued.
• The wet granules are then dried in the heated
fluidizing air stream.
Advantages
• It reduces product loss.
• It improves worker safety.
Disadvantages
• time consuming.
• Difficulty of assuring reproducibility

24. 4. Double cone granulator

25. • Its principle based on double cone mixer.
• The whole unit is rotated along the axis.
• This blender supplied with vacuum which reduce
inside atmospheric pressure.
• Inside the double cone chopper blades are present
which used for granulation.
Advantages:
By using vacuum, granules of heat liable substances
are prepared.

26. • The machine have a stainless steel mixing bowl
containing three bladed impeller and auxiliary
chopper blade.
• The main blade rotate about 150-300 rpm and high
speed chopper blade at about 1500-3000 rpm.
5. Diosna mixer granulator

27. • The high-shear wet granulation process using high-
shear granulator can be divided into 5 stages and
they included;
1. Powder mixing
2. Binder addition or addition of granulating liquid.
3. Wetting of powder and nucleation
4. Growth of granules and densification of the powder.
5. Granule attrition and breakage.
A typical time sequences for the use of Diosna mixer
are as follows:
Mixing: 2 min or less,
Granulating: 8 min or less,
for discharge: one min

28. • It is widely used in pharmaceutics for the granulation
purpose.
• The principle of mixing of powder is based on
convicting mixing mechanism.
Advantages:
• Complete closed system
secures environmental
protection.
• No damage to heat
sensitive products.
• Important savings by
combining operations
such as mixing, drying
and granulation.
6. Day Nauta mixer processer

29. •It was developed in Austria for the preparation of
granules and coated particles under high vacuum.
•The material placed in chamber which must be dust
free suction. Then compartment is loaded by vacuum,
granulating fluid or addition products.
• Under vacuum granulation
force are increased greatly
increase to produce the
the necessary compaction.
Resulted agglomerated particles
dried under vacuum in chamber.
Advantage is low requirement
of granulating fluid.
7. Topo vacuum granulator

30. 8. Chilsonator (Roller compacter)

31. • Chilsonator machine used for dry granulation.
• Formation of dry granules requires dry powder
densification and for agglomeration.
Construction and Working
• Feeding system
• A size reduction unit
• Fixed roller compactor
• Variable gap roller compactor
Advantages
• It is used in granulating thermo labile drugs.
• Moisture sensitive drugs like Aspirin, vitamins are
granulated by dry granulation.
• Those drug do not compress well after wet
granulation.