Pharmaceutical Dosage Form And Science Assignment

Kohat University of Science and Technology Kohat

KUST

Submitted to Dr Sajid Hussain Sir

Submitted by Abdul Wahid

Assignment Dosage Form and Science

Registration no PHR120192003

Date 21 April 2021

Semester 4th Pharm D

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 Pharmaceutical Dosage Form And Science Assignment

A. Wet granulation

Introduction

Wet granulation is the process of binding different powder particles together using
adhesives or liquid solution. All these occur under the action of an impeller.
Basically, this process does not depend on any compressive forces to form
granules. It is quite different from the roller compactor granulation process. As you
will learn later in this section, granulation is a critical procedure in pharmaceutical
and food processing industries. Mostly, you have to granulate powders before
subsequent processing in the capsule filling machines or tablet press machines.

Stages in wet granulation

Broadly, the granulation process involves the following critical stages:

1) Preparing material for Granulation

2) Wetting the powder/Add granulation solution
3) Agglomeration process
4) Drying process

1. Preparing Material for Granulation

This is the first stage in wet or dry granulation process. There are quite a number of
pharmaceutical machines you can use in material processing. These can
include hammer mills, vibro sifter, IBC bin blenders, ovens, milling machines, etc.
In short, there are hundreds of pharmaceutical machines in the market you can use
to prepare materials ready for agglomeration. Preparing material ready for

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granulation Remember, the complexity of a wet granulation technique depends on

the specific ingredients and characteristics of the material. Some of the key
elements you must evaluate when choosing material for wet granulation include:

1) Compressibility
2) Moisture content
3) Particle size
4) Hardness
5) Porosity
6) Bulk density

Of course, this should also go hand-in-hand with choosing the right wet
granulation machine. With an appropriate powder, you can proceed to the charging
process. That is, the process of adding powder into the granulation chamber ready
for agglomeration. The impeller and the chopper will then begin to rotate. To
optimize the mixing process, the machine should have a counter flow setup. This
will allow for good mass movement and homogenous mixing of the material. Once
the mixture is ready, it is now time to proceed to the next stage:

2. Add Granulation Solution

Granulation solution will facilitate the agglomeration process. In most cases, you
can choose from either organic solvents or aqueous granulation liquid. This will
depend on the type of material you intend to process in the granulation machine.

 Aqueous solution as granulation liquid

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Generally, this granulation solution is eco-friendly, affordable and non-

flammable. On the other hand, it has longer drying time and may affect the
stability of the final product. A good example of an aqueous solution is water.

 Organic solvents as granulation liquid

Organic solvents are suitable for moisture sensitive products. They are also
volatile, a reason why they dry faster. However, they are more expensive and may
be harmful to the environment. It is for this reason that you must dispose organic
solvents properly after granulation process. Some examples of organic solvents
include ethanol or isopropanol. Therefore, you will add granulation binder fluid
when the powder is under the influence an impeller. That is, the impeller will be
rotating. In most cases, the granulation machine will spray the granulation solution
from the top. Depending on the design of the granulation machine, you can add
powder as foam or spray. In most drugs manufacturing processes, adding the
granulation binder fluid as foam guarantees consistency and predictable
distribution of the solution. Now, it is at this point that particles begin to bind
together – initial stage of the actual agglomeration process. At times, you can also
refer this process as powder wetting in the wet granulation process.

3. Agglomeration Process or Nucleation

The impeller will continue to rotate as you add the granulation binder solution. At
this point, small granules begin to form. We refer to these small groups of particles
as nuclei. As you add more granulation solution, the granules will increase in size
as they collide with other powder particles. Granulation process This process will
continue until you have a suitable size of the granules. It is this consistent growth
in the size of small granules that we refer to as nucleation. Still, this is not the final

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product. This is because the granules at this stage have a granulation liquid – they
are basically “wet or moist”.

4. Drying Granules Process

You need efficient drying equipment that can remove all granulation liquid or
binder solution. Here, you can choose any of the following possible drying options:

 Pharmaceutical or Tray Drying Oven although pharmaceutical drying

oven is a common drying technique, it is labor intensive. Besides, some
ovens may produce granules with varying porosity, composition and density.
This is due to the non-uniform drying phenomenon.

 Fluid bed dryer Fluid bed dryer dries granules faster than pharmaceutical
ovens. Moreover, they ensure uniform drying. At times, this process may
result in material loss via attrition.

Advantages of Wet Granulation Process

Some of the main advantages of wet granulation process include:

1) It improves the flow properties of materials. In this granulation technique,

you can easily increase the granule size with the moisture content. As a
result, it is easier to increase the followability of the final granule. For
example, you can adopt this granulation process to increase the followability
microcrystalline cellulose.
2) Improves material compression and densification characteristics. You can
easily produce very dense granules by using a high shear mixer or
granulator.

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3) Obtaining homogenous mixture is easy. From the rotating impeller to adding

granulation liquid, you can easily produce homogenous granules. This is
because the action of high shear granulation machines makes it easier for
even and better distribution of particles.
4) Reduces air pollution both aqueous solutions and organic solvents reduce
dust, which could otherwise cause air pollution. Remember, these
granulation solutions also eliminate any possible generation and
accumulation of static charges.
5) In addition to these, the granulation process reduces cross contamination and
allows for better powder handling without compromising on homogeneity.
The modern wet powder granulation process is more cost effective and
efficient than the old techniques. This makes it a perfect choice for quite a
number of material processing procedures in the pharmaceutical industry.

B. Dry granulation

Introduction

Dry granulation also referred to as pre compression or double compression is a size

enlargement process designed to improve the flow and compression characteristics
of powders that would otherwise be unsuitable for compression. The process
involves compaction of powder particles into large pieces or compacts which are
subsequently broken down into granules to produce granules that can be further
processed into dosage forms. Dry granulation is typically used in the manufacture
of tablets if the formulation ingredients are too fluffy or too susceptible to flow
ability problems for direct compression to be a viable processing option and/or too

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susceptible to degradation from heat and/or moisture for wet granulation to be a

viable processing option for densification. The process is sometimes chosen as an
alternative to wet granulation when direct compression is not feasible not
because wet granulation is not feasible but because the manufacturer is more
experienced with dry granulation or to reduce processing time and/or equipment
requirements to reduce costs.

The manufacture of tablets by dry granulation method eliminates a number of unit

operations but still include milling or micronization of drugs, weighing, mixing,
slugging, dry screening, lubrication, and compression of granules into tablets. For
successful manufacture of tablets using dry granulation, either the active ingredient
or the diluent must have sufficient inherent binding or cohesive properties.

Methods of dry granulation

Formation of granules using dry granulation process is generally achieved either by

slugging technique or roller compaction. The two techniques are similar but they
can give different results.

Slugging technique

This process involves compression of primary powder particles into large flat
tablets or pallets using a tablet press or, more usually, a large heavy-duty rotary
press. The resultant compact is then milled using a hammer mill or
other conventional milling equipment. The milled slugs are passed through a
screen of desired mesh for sizing. Lubricant is added in the usual manner, and the
granules compressed into tablets.

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Slugging results in considerable dust production which poses a problem for good
containment and reduction of cross-contamination. Other main shortcomings of
slugging include batch processing, low throughput (30–50 kg/hr), poor process
control, and frequent maintenance changeovers and poor economy of scale. The
method is being replaced by the more modern, and better, roller compaction
process.

Roller compaction

Roller compaction (also referred to as ribbon blending) is a relatively simple, more

efficient and inexpensive form of dry granulation. It is a process where formulation
ingredients are continuously passed between two counter-rotating rollers where it
is densified and consolidated into a sheet of solid mass. Depending on the type of
rollers used, the feed material may be compacted into dense ribbon-like materials
known as flakes (smooth rolls) or dense briquettes (almond or stick-shaped) if the
rollers have grooved or etched surfaces. The compacted materials are further
milled, sized, lubricated and compressed into tablets.

Roller compaction offers distinct advantages over wet granulation, particularly for
moisture-, solvent-, or heat sensitive formulation ingredients. In the pharmaceutical
industry, it is an attractive granulation alternative as it offers considerable cost
savings due of its high production throughput (up to 100,000 kg/hr), shorter cycle
times and fewer processing steps. Moreover, elimination of a drying step reduces
production and development time as well as ease of scale-up.

Excipients used in manufacture of tablets by dry granulation

method

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The types of excipients used in the manufacture of tablets by dry granulation

method and the rationale for their use are similar to those described in the
article “Excipients Used in the Manufacture of Pharmaceutical Tablets”. Typically,
the following excipients are required:
1) Diluent/filler, e.g., microcrystalline cellulose (MCC), anhydrous lactose or lactose
monohydrate, dibasic calcium phosphate, starch etc.

2) Disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, pregelatinized

starch 1500, crospovidone, starch, MCC, etc.

3) Lubricants, e.g., stearates (magnesium stearate, stearic acid), glyceryl fatty acid
esters (glyceryl behenate, glyceryl palmitostearate), Polyethylene glycol (PEG),
polyoxyethylene stearates, sodium lauryl sulphate.

4) Glidants, e.g.: talc, colloidal silicon dioxide.

5) Miscellaneous excipients such as colourants, flavourant, sweetening agents, etc.

Steps involved in dry granulation

A summary of the various steps used in the manufacture of tablets by dry

granulation method is detailed below.

1. Weighing formulation ingredients

Here, appropriate quantities of formulation ingredients are dispensed. The

excipients and the active ingredient(s) must be in finely divided form, otherwise,
particle size reduction should be carried out.

2. Mixing of formulation ingredients

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The dispensed formulation ingredients are mixed in a powder mixer until a

uniform powder mix is achieved. It is worth noting that half amount of lubricant in
the formula is added at this stage to enhance powder flow during slugging and to
prevent sticking of compressed powder on the die during precompression.

3. Compression of mixed powders into slugs

Here, the mixed ingredients are compressed into flat large tablets or pallets. This
step is called recompressions (slugging) and the compacts made in the process
(typically 25 mm diameter by about 10–15 mm thick) are termed slugs.

Compression of mixed powders into slugs can be achieved either by slugging

technique or roller compaction. The pressure used to produce the slugs is usually
less than that used in the final compression.

4. Milling and sieving of slugs

Following slugging, the next stage in the manufacture of tablets by dry granulation
usually involves breaking of slugs into smaller pieces using a hammer mill or other
conventional milling equipment. The milled slugs are screened to produce uniform
granules.

5. Mixing with disintegrant and lubricant

After screening, the remaining lubricant and other extra granular excipients such as
disintegrant, glidant etc., are added to the granulation and mixed gently to achieve
a uniform blend.

6. Compression of granules into tablets

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The mixed granules are compressed into tablets using either single or rotary tablet
press fitted with appropriate punches and dies.

Similar to wet granulation, tablets manufactured by dry granulation method may be

coated if the need arises.

Advantages of dry granulation

As with wet granulation, there are several advantages associated with dry
granulation and they include:
1. Dry granulation requires less equipment and minimum floor space.

2. The process eliminates the addition of moisture and allows dry handling of
moisture sensitive formulation ingredients.

3. The process is suitable for heat sensitive materials since no drying step is involved.

4. Dry granulation is not generally associated with alterations in drug morphology

during formulation process.

5. The process does not require special excipients that are; it makes use of
conventional grades of excipients.

6. Tablets manufactured by dry granulation method have improved disintegration

time because the dry binder used has less adhesive effect thus fast disintegration.

7. The process is easily scaled up from development to production.

8. It improves blending since there is no migration.

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References
1. Allen L. V and Ansel H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery
Systems. Philadelphia: Lipincott Williams and Wilkins.

2. Ennis, B. J. and Litster, J. D. (1997). Particle enlargement. In R. Perry and D. Greens

(Eds.), Perry’s Chemical Engineer’s Handbook. 7th ed. (pp 20-89). New York: McGraw Hill.

3. Jones D. (2008). Fasttrack Pharmaceutics – Dosage Form and Design. London: Pharmaceutical
Press.

4. Ofoefule, S. I. (2002). Textbook of Pharmaceutical Technology and Industrial Pharmacy.

Nigeria: Samakin (Nig) Enterprise.

5. Parikh, M. (2010). Handbook of Pharmaceutical Granulation Technology (3rd ed.). USA:

Informa Healthcare.

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