Method of preparation of tablet Dry granulation

Introduction
In dry granulation process the powder mixture is compressed without the
use of heat and solvent. It is the least desirable of all methods of
granulation. The two basic procedures are to form a compact of material by
compression and then to mill the compact to obtain a granules. Two
methods are used for dry granulation. The more widely used method is
slugging, where the powder is precompressed and the resulting tablet or
slug are milled to yield the granules. The other method is to precompress
the powder with pressure rolls using a machine such as Chilosonator.

Advantages
The main advantages of dry granulation or slugging are that it uses less
equipments and space. It eliminates the need for binder solution, heavy
mixing equipment and the costly and time consuming drying step required
for wet granulation. Slugging can be used for advantages in the following
situations:
i) For moisture sensitive material
ii) For heat sensitive material
iii) For improved disintegration since powder particles are not bonded
together by a binder
Disadvantages
i) It requires a specialized heavy duty tablet press to form slug
ii) It does not permit uniform colour distribution as can be
iii) Achieved with wet granulation where the dye can be incorporated into
binder liquid.
iv) The process tends to create more dust than wet granulation, increasing
the potential contamination.

Steps in dry granulation

i) Milling of drugs and excipients

ii) Mixing of milled powders
iii) Compression into large, hard tablets to make slug
iv) Screening of slugs
v) Mixing with lubricant and disintegrating agent
vi) Tablet compression
Two main dry granulation processes
Slugging process
Granulation by slugging is the process of compressing dry powder of tablet
formulation with tablet press having die cavity large enough in diameter to
fill quickly. The accuracy or condition of slug is not too important. Only
sufficient pressure to compact the powder into uniform slugs should be
used. Once slugs are produced they are reduced to appropriate granule
size for final compression by screening and milling.
Factors which determine how well a material may slug
i) Compressibility or cohesiveness of the mater
ii) Compression ratio of powder
iii) Density of the powder
iv) Machine type
v) Punch and die size
vi) Slug thickness
vii) Speed of compression
viii) Pressure used to produce slug

Roller compaction
The compaction of powder by means of pressure roll can also be
accomplished by a machine called chilsonator. Unlike tablet machine, the
chilsonator turns out a compacted mass in a steady continuous flow. The
powder is fed down between the rollers from the hopper which contains a
spiral auger to feed the powder into the compaction zone. Like slugs, the
aggregates are screened or milled for production into granules.

Formulation for dry granulation

The excipients used for dry granulation are basically same as that of wet
granulation or that of direct compression. With dry granulation it is often
possible to compact the active ingredient with a minor addition of lubricant
and disintegrating agent. Fillers that are used in dry granulation include the
following examples: Lactose, dextrose, sucrose, MCC, calcium sulphate,
Sta-Rx etc.
Examples of some tablet formulation prepared by dry granulation

Disadvantages of dry granulation

Specialist equipment is required for granulation by roller compaction.
Segregation of components may occur post mixing.
There may be issues regarding powder flow.
The final tablets produced by dry granulation tend to be softer than
those produced by wet granulation.
Slugging and roller compaction lead to the generation of
considerable dust.
Advantages of Dry Granulation:
- Minimal floor space
- Large throughput of material (highly efficient process)
- Continuous process
- Highly energy efficient; no heat for drying and no air conditioning required
as for other granulation techniques
- Ultra High Containment Options are available to avoid contamination of
manufacturing areas and personal by high potent actives

- Low running costs

Introduction
Granulation may be defined as a size enlargement process which converts
small particles into physically stronger & larger agglomerates.
Granulation meth

INTRODUCTION
In general direct compression method involves the

direct compaction of tabletting mixture without the

step of granulation, provided the tabletting mixture
should have enough flow properties and should form
a robust tablet. For suppose, if the tabletting mixture
is not having good flow properties, we can either use
direct compression vehicles (DCV) for improving the
flow and compatibility of tabletting mixture or by
subjecting the mixture for granulation process(wet or
dry granulation).
DIRECT COMPRESSION:
This method involves simple blending of active
pharmaceutical ingredient (API) with other
ingredients and direct compaction of the resultant
mixture.
(a.)Advantages of Direct compression:
1. Cost Effectiveness: The prime advantage of direct
compression over wet granulation is economic since
the direct compression requires fewer unit operations.
This means less equipment, lower power
consumption, less space, less time and less labor
leading to reduced
production cost of tablets.
2. Stability: Direct compression is more suitable for
moisture and heat sensitive APIs, since it eliminates
wetting and drying steps and
increases the stability of active ingredients. Changes
in Dissolution profiles are less likely to occur in
tablets made by direct compression on storage than in
those made from granulations.
3. Faster Dissolution: Disintegration or dissolution
is the rate limiting step in absorption in case of
tablets with poorly soluble API prepared by wet
granulation. The tablets prepared by direct
compression disintegrate into API particles instead of
granules that directly come into contact with
dissolution fluid and exhibits comparatively faster
dissolution.
4. Lubricant sensitivity: Lubricants have more

adverse effect on the filler, which exhibit almost no

fracture or shear on compression (e.g. starch 1500).
The softening effects as well as the hydrophobic
effect of alkaline stearates can be controlled by
optimising the length of blending time to as little as
2-5 min.
5. Variation in functionality: There is a lack of
awareness in some situations that the excipient
behave differently, depending upon the manufacturer
so much so that substitution from one source to that
of another is not possible. Hence, there is a need for
greater quality control in purchasing of raw materials
to assure batch uniformity.
(b.)Limitations of Direct compression:
1. Segregation: Direct compression is more prone to
segregation due to the difference in density of the
API and excipients. The dry state of the materials
during mixing may induce static charges and lead to
segregation. This may lead to the problems like
weight variation and
content nonuniformity.
2. Cost: Directly compressible excipients are the
speciality products produced by spray drying, fluid
bed drying, roller drying or co-crystallization. Hence,
the products are relatively costly than the respective
raw materials.
3. Low dilution potential: Most of the directly
compressible materials can accommodate only 30-40
% of the poorly compressible active ingredients like
acetaminophen that means the weight of the final
tablet to deliver the 500 mg of acetaminophen would
be more than 1300 mg. The large tablets may create
difficulty in swallowing.
4. Lubricant sensitivity: Lubricants have more
adverse effect on the filler, which exhibit almost no
fracture or shear on compression (e.g. starch 1500).
The softening effects as well as the hydrophobic
effect of alkaline stearates can be controlled by
optimising the length of blending time to as little as

2-5 min.
5. Variation in functionality: There is a lack of
awareness in some situations that the excipient
behave differently, depending upon the manufacturer
so much so that substitution from one source to that
of another is not possible. Hence, there is a need for
greater quality control in purchasing of raw materials
to assure batch uniformity.
(c.)Formulation: General formula for direct
compression includes the following ingredients1.Binder-Filler (DC-vehicles): These DC vehicles
(either binders or fillers) play an important role as
that of API in this method. In general, the terms
binder and filler are always confusingly used in direct
compression. But, the major difference between these two is their Dilution
capacities. (Dilution capacity is
the maximum proportion of the API that can be
compacted into an acceptable compact by the binder
or filler.)Binders have high dilution capacity as these
are more compactible where fillers have less dilution
capacity due to their less compatibility nature. But,
these values vary depending upon the compacting
ability of the API used.
API
DC-binder
DC- filler
Disintegrant
Lubricant
Others
In general, dilution capacity values of binders and
fillers are determined by using some reference
materials which are difficult to compact.
Eg: ascorbic acid.
Based upon the solubility and disintegration
properties of the Binders, these can be classified as1. Soluble Binders: These are always nondisintegrating.
Some of the examples are

Sugars, Ploy hydric alcohols etc.

2. Insoluble Binders: These insoluble binders
are again of two typesa.
Disintegrating
(MCC, starch etc.)
b. Non-disintegrating
(DCP)
When we use soluble filler, there will be rapid
release of API from the tablet, but the problem is that
soluble erosion and release profile dominates the
disintegration and release profile. (We observed
faster release patterns in case of MCC tablets when
compared with similar formula where lactose is used
instead of MCC).
Factors influencing the selection of optimum DCvehicle:
1. Properties of Powders. (particle size,
shape, density, solubility)
2. Properties of compacts. (flow,
compatibility)
3. Stability factors. (temperature and
moisture effects)
4. Others. (cost, availability etc.)
2. 2. Disintegrants: In general, we use less
concentration of disintegrants in DC method when
compared with the wet granulation method which are
nothing but super disintegrants. This can be
explained by following reasons-To minimize the
softening and flow properties of the tableting
mixture. The required uniform particle size of APImixture. The required uniform
particle size of API
upon disintegration can be achieved only if the
disintegrant used is uniformly distributed in the
tablet, which may be difficult when high loadings of
API are used. Also when we use soluble fillers,
erosion followed by dissolution occurs instead of
disintegration, which can be avoided if we use more
concentration of disintegrant or super disintegrants.
Some of the examples of super disintegrants are
sodium starch glycollate, crosspovidone,
crosscarmellose etc. Though starch is not a super

disintegrant, we use it in DC because it can also be

used as DC filler.
3. Lubricants: We prefer hydrophilic lubricants over
the hydrophobic ones in case of DC method. This is
because, hydrophobic ones (magnesium stearate)
may form a film around other ingredients used in the
formula which may results in the decrease of tablet
hardness. This problem can be overcome by
following by
a. Blending the tableting mixture (excluding
lubricant) by high shear mixtures and then adding the
lubricant to this main blend with low shear mixing.
b. By carefully controlling the particle size and
surface area of the lubricant used.
c. Use of hydrophilic lubricants such as stearic
acid, stearyl fumerate, hydrogenated vegetable oils
etc.
u
Preparation of DC-vehicles:
As we have already discussed that DC excipients are
speciality products prepared by modification of
normal ingredients, these modification can be done in
two ways:
1.Chemical modification: Ethyl cellulose,
Methyl cellulose, HPMC, Na-CMC,
Cyclodextrins etc.
2.Physical modification: Dextrates or
compressible sugars, sorbitol, DCP etc.
3.Spray drying: MCC, Emdex, Spray dried
Lactose etc.
4. Crystallization: Dipac etc.
5.Granulation: Tabletose (granulated lactose) etc.
6. Co-processing:
Cellactose: MCC, Lactose.
Ludipress: Lactose, PVP, Crosspovidone.
Starlac: Lactose, Maize starch.

REFERNCES
1. Herbert A.Liberman, Leon Lachman, Volume-1,
2nd edition, Pharmaceutical dosage forms, Tablets.
2. Khan K A, Rhodes C T. The Production of Tablets
by Direct Compression, Can. J. Pharm. Sci.1973;
8: 1-5.
3. Shangraw R F, Demarets D A. Survey of Current
Particles in the Formulation and Manufacture of
tablets and Capsules. Pharm. Technol 1993; 17:
32-44.
4. Robertson M I. Regulatory Issue with Excipients.
Int. J. Pharm.1999; 197: 273-276.
5.Gonnissea Y, Remona J P, Vervaet C.
Pharmaceutical excipient having improved
compressibility. Europian J. Pharma. 2007; 67:
220-226.
5. Jogani P D. Gohel M C Review of coprocessed
DC. Excipients. J. Pharm. Sci.2005; 8(1): 76-93
6. Gonul N. The Consolidation and compressibility
Property of some novel directly compressible
Binders & fillers. Ankara University, Acta Pol
Pharm.2000; 57(4): 311-317.
7. Parot E L, Lachman L, Liberman H A, Kanig J L.
Eds Lea and febiger. Theory and practice of
Industrial Pharmacy.1986; 3: 21-46.
8. Fiese E F, Hagen T A, Lachman L, Liberman HA,
Kaninig J L, Eds Lea and Febiger.
Preformulation, Theary and Practise of Industrial
Pharmacy.1986; 3: 171-194.
9. Aulton M E, Cellulose Powdered, in Handbook of
Pharmaceutical Excipients, Rowe R C., Weller P
J., Eds., The Pharmaceutical Press, UK., 2003;
112-114.

CONCLUSION:
As discussed earlier, the major challenge for tablet
manufacturing comes from the powder flow
properties and compressible characteristics of the
materials to be compressed. This in turn poses a
challenge in achieving greater productivity and better
quality product especially on the new generation
high-speed machines. The conventional method of
wet granulation has inherent drawbacks in terms of
achieving batch-to-batch reproducibility and higher
productivity, especially in low particle size range.
Compared to wet granulation, direct compression
requires fewer processing steps, offers simplified
validation and results in product with better stability.
Hence, Direct co