1. Technical session 2012
Problems during Granulation
,Compression
&
Saima Naz
(Production Officer)
Oral Solid Mfg
their Rectification

2. Introduction

Granulation & Compression are two processes used in
tablet formulation.

Both granulation & Compression affect the final dosage
form.

So it is important that proper Granulation &
Compression must be done to produce tablet of good
quality, strength, hardness.

3. Granulation
“ Granulation is the process of collecting particles
together by creating bonds between them. Bonds are
formed by compression or by using a binding agent.”

4. Granulation

Granulation in pharma industry is of two types;
1.
Wet Granulation
2.
Dry Granulation

Pharmaceutical products are processed all over the world using the
wet-granulation, or dry-granulation methods. Which method is
chosen depends on the ingredients’ individual characteristics and
ability to properly flow, compress, eject, and disintegrate. Choosing
a method requires thorough investigation of each ingredient in the
formula, the combination of ingredients, and how they work with
each other. Then the proper granulation process can be applied.

5. Granulation
In the pharmaceutical industry, most products are
manufactured using the wet granulation process. Wet
granulation offers a wide range of capabilities for
forming granules, from the production of light granules
to the production of very dense granules. More than
70% of the global industry’s granulations are made
using this method.

6. Importance of granulation
A tablet with good characteristics is not made on a tablet press; it
is made in the granulation process. Joining particles within a
given granulation process will improve;

flow and compression characteristics

reduce segregation

improve content uniformity

eliminate excessive amounts of fine particles.

7. Importance of granulation
The results will be

Improved yields

Reduced tablet defects

Increased productivity and

Reduced down time.
The objective of the process is to combine
ingredients to produce a quality tablet.

8. Why granulation?
When powders are very fine, fluffy, will not stay
blended, or will not compress, then they must be
granulated. Fluffy is not a technical term, but it fits
the problem well; it means that the required
quantity of powder physically will not fit into the die
cavity on the tablet press. The volume of fill (bulk
density) is greater than that which is mechanically
allowed.

9. Wet granulation

“Traditional wet granulation, is the process of mixing
and adding solution(wet massing) and then transferring
the product to FBD/& Tray dryer.”

“Wet massing is the process of adding a solution to a
blended powder and mixing for a predetermined period
of time at a given mechanical speed”
The process can be very simple or very complex
depending on the characteristics of the powders, the
final objective of tablet making, and the equipment that
is available.

10. Instruments used in wet granulation

Mixer & granulator: for wet mixing

FBD & Tray dryers: for drying of granules

Oscillating granulator: for granulation of dried
mass

MDM mixer: for lubrication

11. Compression



“It is the process by which prepared granules are
compacted into the core tablet form.”
Instrument use for compaction of granules is called
rotary press compression machine.
Dies & punches are used to give shape , strength,
weight adjustment & hardness to tablets. Because
granules are filled in dies & punches compressed
them.

12. P R O B L E M S D U R I N G G R A N U L AT I O N
& COMPRESSION

Problem that we face at granulation phase are;
1.
Density of Granules: if speed of granulator & mixer is very
high & optimum time is not given for “mixing &
granulation” of raw material, too dense or very low dense
granules are formed. Too dense granules lead to prolong
disintegration time. Very less dense granules not obtain
proper disintegration time. so density of granules should
be optimum. For optimum density the speed of “mixer &
granulator” & time for which mixing & granulation is done
should be controlled… if speed of mixer & granulator is
slow , more time require to produce optimum density
granules & vice versa. Speed & time also important for
uniform mixing of all ingredients.

13. Problems during granulation &
compression
2. Drying of granules: Too much dry granules loose
all moisture & during compaction process tablets
not achieve the required strength & my be caped or
show lamination & if drying of granules is not
proper ..wet mass lead to sticking of granules with
punches & adhered to dye.. So drying of granules
should be optimum. For proper & optimum drying
the temperature of FBD & timing for drying should
be taken in account & controlled.. Some materials
are hygroscopic in nature. they are almost
complete dried & very less moisture level
(approximately < 1% ) should be retained in them.

14. Problems during granulation &
compression
3. Content uniformity: During lubrication stage, the
mixing time for lubrication must be proper & controlled.
Because this is the stage after which granules are going
to be compacted into tablet form.. If mixing is not
proper the content uniformity of active in tablet is not
achieved & flow of granules into the dies also affected
& improper flow lead to weight variation of tablet.

15. Problems during granulation &
compression

Tablets defects appeared during compression
process are mostly related with granulation stage &
little with compression stage.

Problem that we face at compression phase are of
two types;
One are those which relates with rotary press
efficacy & operator.
1.
2nd are those which comes in tablet during
compression because of problems in granulation
phase.
2.

16. Characteristics of ideal tablets
1- Free of defects ,such as chips ,cracks ,discoloration
&contamination
2-Have the strength to withstand the mechanical stress of production
3-Chemically & physically stable over time
4-Release the medicinal agents in a predictable& reproducible manner

17. Problems during granulation & compression

Problems in tablets are;
1.
Sticking
2.
Picking
7. Disintegration time
3.
Capping
8. Hardness
4.
Lamination
5.
Weight variation
6.
Double impression

18. Problems during granulation &
compression
Sticking: is adhesion of tablet material to a die wall. this is the
defect in tablet in which granules are Sticked in die of rotary press &
tablets ejection becomes difficult & Punches required greater force
to eject the tablet. As a result of it, edges of tablets are broken down
during ejection. Tablet show pitted surface rather than smooth
surface.
1.

Reasons:
I.
Too wet granules
II.
Wear off punches
III.
Proper cleaning of punches is not done.
IV.
Lubrication is not proper
V.
Substances with low melting temperatures in the formulation

19. Problems during granulation &
compression

Sticking Rectification:
I.
Proper cleaning & polishing of punches should be done
by operator.
II.
Wear off punches must be replaced with newer ones. &
proper cleaning & maintenance of punches, dies &
machine must be done by operator.
III.
Proper Lubrication of punches & of granules must be
done.

20. 
Sticking, Picking & Filming:

Adhesion of the material to the punch faces.

•
Sticking : (whole adhesion)


is usually due to improperly dried or lubricated granulation causing the whole
tablet surface to stick to the punch faces → dull, scratched, or rough tablet
faces.


•

is a form of sticking in which a small portion of granulation sticks to

the punch face & a portion of the tablet surface is missed.
Picking : (localized adhesion)


Filming: is a slow form of sticking and is largely due to excess moisture in the
granulation
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21. Problems during granulation &
compression
2. Picking: is removal of a tablet’s surface material
by a punch. In this case a cavity is appeared on
tablet surface.

23. 
Capping & Laminating:


Capping occurs when the upper segment of the

tablet separates from the main portion of the tablet &

comes off as a cap.

-
Most annoying problem

-
Can appear immediately after compression, or hours, even days after preparation.

•
It is usually due to air entrapped

in the granulation which is compressed

in the die during the compression & then expands when the pressure is released.
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25. 
Reasons of capping :

1. large amount of fines in the granulation &/or the lack of sufficient
clearance between the punch and the die wall.


2. In new punches and dies that are tight fitting.


3. Too dry granules.

Lamination is due to the same causes as capping except that the tablet
splits at the sides into two or more parts.

If tablets laminate only at certain stations, the tooling is usually the cause.
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26. 

Solutions for capping & laminating:
1. Increasing the binder.


2. Adding dry binder such as gum acacia polyvinylpyrrolidone (PVP).

3.Decreasing the upper punch diameter.


4. Certain degree of moisture in the granules
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27. 
4. Mottling:

It is an unequal distribution of color on the surface of the tablet.

Cause :

1. A drug that differs in color from its excipients or whose degradation
products are highly colored.


2. Migration of a dye during drying of a granulation (change the solvent
system, reduce the drying temperature, or grind to a smaller particle
size).
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