DEFINITION - Particle size enlargement is agglomeration of fine powder particle to form uniform granule. Size- 0.5 to 2.0mm

1. 4/28/2016 Sagar Kishor Savale 1
Department of Pharmacy (Pharmaceutics) | Sagar savale
Particle Size Enlargement
Techniques
Mr. Sagar Kishor Savale
[Department of Pharmaceutics]
avengersagar16@gmail.com
2015-2016

2. Contents
• DEFINATION
• INTRODUCTION
• FORCES
• ADVANTAGES
• DISADVANTAGE
• METHOD OF PREPARATION
• REFERENCE
4/28/2016 Sagar Kishor Savale 2

3. INTRODUCTION
• DEFINITION - Particle size enlargement is agglomeration of fine powder
particle to form uniform granule.
• Size- 0.5 to 2.0mm
• FORCE INVOLVED IN PARTICLE SIZE ENLARGEMENT
 INTERMOLECULAR FORCES:
LONDON DISPERSION FORCES/ DISPERSION FORCES
These forces are due to particle-particle adhesion, & exhibited when the
separations distance is less than 10-3 A0.
4/28/2016 Sagar Kishor Savale 3

4.  ELEECTROSTATIC FORCE:
It exist either as a result of interparticular friction or
through the generation of opposite charge.
 LIQUID & SOLID BRIDGES:
Dispersing liquid into a powder mass will generally
result in a significant increase strength of particle-
particle agglomerates.
4/28/2016 Sagar Kishor Savale 4

5. METHOD OF PARTICLE SIZE
ENLARGEMENT
• PELLITIZATION PROCESS
1. Powder Layering
2. Solution or Suspension Layering
3. Spray Drying & spray Congealing
4. Cryopelletization
5. Extrusion – Spheronization
• CRYSTALLIZATION
• GRANULLATION
A) Wet Granulation
B) Dry Granulation
4/28/2016 Sagar Kishor Savale 5

6. ABOUT PELLETS
• Pellets are free flowing spherical units prepared
from fine particle powder.
• Size- 0.5 to 1.5mm
• For oral drug delivery/control drug delivery.
• Coated pellets are administered in the form of
soft gelatin capsule or disintegrating tablet so
that they remove to content in gastric
environments.
• Shows their flexibility in different formulations.
4/28/2016 Sagar Kishor Savale 6

7. PROPERTIES
• Excellent stability
• Dust free round pallets
• Good flow bahaviour
• easy to dose
• Compact structure
• Low Hygroscopicity
• High bulk density
• Dense uniform surface
• High active ingredient is possible
• Controlled release application
• Drug absorption can be alter
• Risk of local damage to the mucosa reduced
4/28/2016 Sagar Kishor Savale 7

8. ADVANTAGES
• Flexibility in the dosage form.
• They can also blended to deliver incompatible
bioactive agent.
• They may be given to provide different release
rate at different site of location.
• Increases drug absorption and decrease
mucosal irritation.
• They have excellent flow property .
4/28/2016 Sagar Kishor Savale 8

9. DISADVANTAGES
• Size may vary formulation to formulation.
• Capsule filling may increase cost and
tabletting may destroy the coating on pallet.
4/28/2016 Sagar Kishor Savale 9

10. PELLETIZATION
• Conversion of powder particle to spherical
particle.
• Size- 0.5-1.5 mm
• Four method for pelletization –
A. Powder layering
B. Solution or suspension layering
C. Spray drying/congealing
D. Extrusion -spheronization
4/28/2016 Sagar Kishor Savale 10

11. POWDER LAYERING
4/28/2016 Sagar Kishor Savale 11

12. FLUIDIZED BED DRYER
1] Detachable
chamber
2] Fluidized bed
3] Fluidized gas &
liquid
4] Blower
5] Heater
6] Filter
7] Filter bag
4/28/2016 Sagar Kishor Savale 12

13. FBD
• Principle-
the bottom contain powder which we have to
pelletized is placed in bowl.
Two nozzles are there (1)hot air
(2)binding agent
Powder lifted from bottom and suspended in air
the condition we called fluidized state.
4/28/2016 Sagar Kishor Savale 13

14. WORKING
•The powder to be pelletized are placed in a detachable
bowl.
• Then it is pushed into dryer fresh air is allowed to pass
through filter which subsequently get heated into heater.
•When the velocity of the air is greater than the settling
velocity of the powder
•the powder remain partially suspended in the gas stream,
then the granule rise in the container because of high
velocity of gas (3-8 m/s)
•Fluidized state: the gas surrounding every forming pellets to
complete them dry & uniform.
the air leaves dryer by passing through the filter. Process
is continued until desired size pellet is formed.
4/28/2016 Sagar Kishor Savale 14

15. SOLUTION AND SUSPENSION
LAYERING
4/28/2016 Sagar Kishor Savale 15

16. WURSTER COATING PROCESS
• It is distinguishing feature from that of powder
layering equipment cylindrical partition
located in the product chamber and
configuration of air to allow most of drying air
to pass at high velocity around the nozzle and
through the particle.
4/28/2016 Sagar Kishor Savale 16

17. WURSTER PROCESSER
4/28/2016 Sagar Kishor Savale 17

18. SPRAY DRYING/CONGEALING
The spray dryer provides the large surface area for heat
and mass transfer by automizing the liquid to small
droplets. these are spread into a steam of hot air so that
each droplet dries to individual solid particles. Thus the
particle formation and drying occur in same process.
4/28/2016 Sagar Kishor Savale 18

19. EXTRUSION-SPHERONIZATION
• EXTRUDER :
now a days three types of extruder present in
the market as follows:
1) Screw-fed extruder
2) Gravity-fed extrude
3) Ram-fed extruder
4/28/2016 Sagar Kishor Savale 19

20. CRYOPELLETIZATION
• Process by which conversion of liquid droplets
into the solid spherical particles by cooling
with nitrogen.
• The pellets are dried in conventional freeze
dryer to remove water and organic solvent.
4/28/2016 Sagar Kishor Savale 20

21. CRYSTALLIZATION
• The spontaneous arrangements of repetitive
orderly array.
• Process of crystallization as follows:
4/28/2016 Sagar Kishor Savale 21

22. SOLUTION SUPERSATU-
-RATED SOL.
Diffusion &
Deposition of
Particle on nuclei
COOLING OF EVAPORATION OF LOOSE
SOLUTION SOLVENT AGGREGATES
(SUPERSATURATE
OR UNSATURATED) ADDITIVES ADDITION OF
CRYSTAL OR CLUSTER
BREAKING OF
WEAK CRYSTAL
Embryo
(LATTICE
ARANGE
MENT)
NUCLEI
CRYSTAL GROTH NUCLEATION
CRYSTALLIZATION
4/28/2016 Sagar Kishor Savale 22

23. CRYSTALLIZATION INVOLVES THREE
STEPS
1. Supersaturation
2. Nucleus formation
3. Crystal growth
4/28/2016 Sagar Kishor Savale 23

24. SUPERSATURATION
• Improve the solubility of the solvent by
providing the energy with external factor such
as
1. Evaporation of solvent
2. Cooling of solution
3. Addition of another substance
4/28/2016 Sagar Kishor Savale 24

25. NUCLEATION
• Formation of small body or new phase in the
solution which has become supersaturated
before .
Crystal growth
• The step is take place by diffusion process.
• The solute molecule reach to the crystal and
lattice are formed.
4/28/2016 Sagar Kishor Savale 25

26. Mire's theory
• Postulates a definite relationship between
conc. And temp. at which crystal will
spontaneously form in unseeded solution.
• According to it, the supersolubility curve
represents the limit at which nucleus
formation begins spontaneously and
consequently the point were crystallization
can start in the absence of any solid particle.
4/28/2016 Sagar Kishor Savale 26

27. CONC
TEMP.
G
F
D
C
P
EB
A NORNAL SOLUBILITY
CURVE
SUPERSOLUBILITY
CURVE
4/28/2016 Sagar Kishor Savale 27

28. Condition for mire's theory
• Solute and solvent must be pure
• Solution must be free from solid solute
particle
• Solution must be protected from entry of
particle
• Soft or weak crystal must not form during
process
• There should not fluctuation in temperature.
4/28/2016 Sagar Kishor Savale 28

29. Limitations
• According to the theory, Crystallization starts
at super solubility curve.
• If solution kept for longer period nucleation
starts below solubilty curve.
• Miers theory applicable when,pure solute and
solvent are used, which impossible.
4/28/2016 Sagar Kishor Savale 29

30. Equipment used in crystallization:
•Agitated batch crystallizer
•Swenson walker crystallizer
•Krystal crystallizer
•Vacuum crystallizer
4/28/2016 Sagar Kishor Savale 30

31. GRANULATION
• Fine particles of powder are come together to
form multiparticle entity.
• Size- 0.2-4.0 mm
Why granulation
• To prevent the segregation of constituent of
powder mixture
• To improve flow properties
• To improve characteristics of mixture
4/28/2016 Sagar Kishor Savale 31

32. Mechanism Of Granule Formation
1. Nucleation
• granulation starts with particle-particle contact and adhesion due to
liquid bridge.
• A no of particle joint to form pendular state, further agitation densities
the pendular bodies to form capillary state and bodies act as a nuclei for
further granule growth.
2. Transition
Nuclei can grow by two possible mechanism
1. Either single particle can be added to the nuclei by pendular bridges.
2. Two or more nuclei may be combine, the combine nuclei will be reshape
by agitation of bed
4/28/2016 Sagar Kishor Savale 32

33. 3. BALL GROWTH
the agitation is continued, granule coalescence will
continue and produce unstable and over mass
system . Although this is dependant upon liquid
added and the particle of material being granule.
4/28/2016 Sagar Kishor Savale 33

34. GRANULATION METHOD
1. Dry granulation
• this require two places of equipment . A machine for
compressing dry powder into compacts and a mill for
breaking of this intermediate product into granule.
• The dry granulation method can be used for drug that do not
compress well after wet granulation or those which are
sensitive to moisture.
4/28/2016 Sagar Kishor Savale 34

35. WET GRANULATION
• In this, wet mass is forced through a sieve to produce
wet granule
• Which are then dried.
• A subsequent are used when water sensitive drug
are processed as an alternative to dry granulation or
when a rapid drying is required (e.g. FBD)
4/28/2016 Sagar Kishor Savale 35

36. REFERENCES
1. Michael e aulton. “pharmaceutics- the design and mfg
of medicine”,3rd edition, Churchill Livingstone, p-p no.
410-422
2. Leon Lachman, Liberman A. “The Theory and Practice
Of Industrial Pharmacy; varghese publishing house ;
Third edition, P-P no. 317-324.
3. C. V. S. Subrahmanyan , “Pharmaceutical
engineering” Vallabh Prakashan, P-P no.360-381.
4/28/2016 Sagar Kishor Savale 36

37. 4/28/2016 Sagar Kishor Savale 37