The document discusses different granulation techniques used in pharmaceutical manufacturing including dry and wet granulation. It describes processes like compression granulation, roller compaction, high shear mixing and fluidized bed granulation. The key purposes of granulation are to improve flow properties, compaction characteristics and prevent segregation of powder constituents.

1. Mr. Sagar N Firke
Dept of
Pharmaceutics
Nanded Pharmacy College,
Nanded, Maharashtra
GRANULATION TECHNOLOGY
(A Concise view)

2. Granulation: “Granulation is the process in which
primary powder particles are made to adhere to form
larger, multiparticle entities called granules”
Why granulation?
To prevent the segregation of the constituents of the powder
mix.
 To improve the flow properties of the mix.
 To improve the compaction characteristics of the mix.
 Prevents dust formation of toxic drugs.
 Granulation may reduce cake formation of hygroscopic
substances.
 Occupy less volume per unit weight.

3. Dry Granulation
Fig: Dry Granulator

4.  Compression granulation involves the compaction of the components
of tablet formulation by means of tablet press and followed by milling
and screening prior to final compaction into tablet.
 Compacted mass is called as ‘slug’ and the process is called as
‘slugging’.
 Compression granulation can also be performed on a specially designed
machine called a roller compactor.
 The compaction force of the roller compactor is controlled by three
variables.
 The hydraulic pressure exerted on the compaction rolls.
 The rotational speed of the compaction roll.
 The rotational speed of the rotating screw.

5. Wet Granulation
 Wet granulation involves the massing of a mix of dry primary
powder particles using a granulating fluid.
 Granulating fluid consist of binder( PVP, Sucrose ,etc) & suitable
solvent( Water, alcohol, etc)
 The fluid contains a solvent which must be volatile so that it can be
removed by drying, and be non-toxic.
 Water is commonly used solvent for economical and ecological reasons.
 Water has disadvantages as a solvent, it may adversely affect drug
stability, it needs a longer drying time than do organic solvents.
 Increases the length of the process and again may affect stability because
of the extended exposure to heat.

6. GRANULATION MECHANISMS
GRANULATION
MECHANISMS
Adhesion and Cohesion
Forces
Interfacial forces in mobile liquid
films
The formation of solid bridges
Attractive forces between solid particles

7.  Adhesion and Cohesion Forces.
 Sufficient liquid is present in a powder to form a very thin,
immobile layer.
 There will be decrease in interparticulate distance and an
increase in contact area between the particles.
 The bond strength between the particles will be increased
because of van-der-Waals forces.
 Films may be present as residual liquid after drying of
granules, ; these films do not contribute significantly to the
final granule strength.

8. Interfacial forces in mobile liquid films
 During wet granulation liquid is added to the powder mix and will
be distributed as films around and between the particles.
 Sufficient liquid is usually added to convert immobile layer into a
mobile film
 There are three states of water distribution
 Pendular
 Funicular
 Capillary

9. Interfacial forces in mobile liquid films
 In Pendular state, the particles are held together by lens-shaped
rings of liquid.
 When all the air has been displaced from between the particles
the Capillary state is reached.
 The Funicular state represents an intermediate stage between
the Pendular and capillary states.

10.  Interfacial Forces in Mobile Liquid Films
Pendul
ar
Funicular Capillary
Droplet
Formation

11. The formation of solid bridges
Partial melting
Hardening binders
Crystallization of
dissolved substances.

12. The formation of solid bridges
Partial melting
Hardening binders
Crystallization of dissolved
substances

13.  Attractive forces between solid particles
 there are two types of attractive force that can operate between
particles in pharmaceutical systems electrostatic forces and
van-der-Waals forces
 Electrostatic forces may be important in causing powder
cohesion and the initial formation of agglomerates, e.g. during
mixing

14.  Mechanisms of granule formation
Nucleation
Transition
Ball Growth

15. GRANULATORS
WET GRANULATORS
Shear Granulator
Ex: Planetary
mixer &
Oscillating
granulator
High Speed
Mixer
Ex: Diosna,
Collette-Grall
Fluidized
Bed
Granulator
Extruder and
Spheronizer/p
elletizer

16. Shear Granulator

17. Shear Granulator
Powder mixing usually has to be performed as a separate operation
using suitable mixing equipment.
The mixed powders are fed into the bowl of the
planetary mixer and granulating liquid is added as
the paddle of the mixer agitates the powders.
The moist mass has then to be transferred to a granulator, such as an
oscillating granulator.
 The mass should be sufficiently moist to form discrete granules.
If excess liquid is added, strings of material will be formed
The granules can be collected on trays and transferred to a drying
Oven.

18. High-speed mixer/granulators (ex. Diosana)
 The machines have a stainless steel mixing bowl containing a three-
bladed main impeller, which revolves in the horizontal
plane, and a three-bladed auxiliary chopper.
 dry powders are placed in the bowl and mixed by the rotating impeller
for a few minutes.
 Granulating liquid is then added via a port
 The chopper is usually switched on when
the moist mass is formed
 Once a satisfactory granule has been produced,
the granular product is discharged, passing through
a wire mesh which breaks up any large aggregates,
into the bowl of a fluidized-bed drier

19.  Fluidized-bed Granulator( Aeromatic)
 FBG have similar design and operation to fluidized-bed driers,
i.e. The particles are fluidized in a stream of air.
 Heated & filtered air is blown through bed of unmixed powder
to fluidized the particles.
 Granulation fluid is sprayed from a nozzle on the bed of powder
helps to adhere the powder particles to each other.
 After sufficient size is achieved spray is turned off and continue
the air supply for the drying purpose.

20.  Advantages
 All the process such as mixing and granulation is done in unit
equipment. Which saves labour cost, transfer losses and time.
 Disadvantages
 Instrument is expensive
 Process optimization requires & needs extensive
developmental work.
 There are numerous apparatus, process & product parameters
need to be fixed.
Ex: Air distribution, Nozzle height, Bed load, Air flow rate ,
Type of binder, Binder solvent etc.

21. Fluidized Bed Granulator

22. Extrusion/Spheronization
 It is a multistep process used to make uniform sized spherical
particles.
 The main steps are
Dry Mixing of ingredients (to achieve a homogenous powder
dispersion)
 Wet Massing ( to form rod shaped particles of uniform diameter)
 Spheronization ( to round off these rods into spherical particles)
 Drying ( To achieve desired final moisture content
 Screening ( To achieve the desired narrow size distribution)

23. Ref: Book “Pharmaceutics, The Science of Dosage form Design "by
M E Aulton. Page No, 376.

24. “An investment in knowledge pays the
best interest”.
Benjamin Franklin