Introduction to Flow Properties of Powder

Powder
‘Powders are generally composed of solid particles of same or different chemicals
composition having diameter less than 1000

Introduction:
The particles flow when the solid particles attract one another by the forces between them.
These forces are predominately the surface forces which can affect the flow properties of
solid.

Types of forces:
There are 5 types of forces that can act between solids. These are
1. Frictional forces
2. Surface tension forces
3. Mechanical forces
4. Electrostatic forces
5. Cohesive or Van der Waals forces.

Flow properties of powders:

The particles of pharmaceutical powders are “free-flowing” or “cohesive (non-free-flowing).
Factors that significantly affect the flow properties of powder are “change in”
1. Particle size and Particle size distribution
2. Particle Density
3. Particle Shape
4. Particle Charge
5. Moisture content and granulation
These changes may arise during the processing or formulation resulting in variation from
free-flowing drug powder to a cohesive aggregate during granulation. So, to overcome
interparticulate interactions an entirely different formulation strategies are required.

Effect of Glidant & Measurement of the flow of powders:

Glidant
‘Glidant are agent which are used to enhance flow properties of powder granules by
reducing friction between powder particles and hopper surface’

Effect of Glidant:
They increase cohesiveness of powder from hopper to die cavity. The increase in powder
flow by glidant has limitation that after certain concentration of glidant it tend to retard flow
properties of material and also effect release pattern of active material from dosage form.

1
Effect of diluent on flow properties is very important; this can be evaluated simply by bulk
density.

Measurement of bulk Density:

Bulk density of powder is dependent on particle paking and charges as the powder is
consolidation. A consolidation powderis likely to have a greater arch strength than a less
consolidation one and therefore it may be more resistant to powder flow. The ease with which
a powder consolidates can be used as an indirect method to determine quantitative powder
flow.
Bulk density can be found by either hausner’s ratio or by carr’s compressibility index.

Measurement of Flow of powders:

Compressibility index and Haunser’s ratio are the techniques that provides a simple
indication of the flowability of powdered material.
The Carr’s index (also called Carr’s index or Carr’s compressibility index) gives an
indication of the compressibility of the powder. It is named after the scientist Ralph J. Carr.
Jr.

 Carr’s Compressibility Index:

A %age compressibility of a powder is a direct measure of the potiential powder arch
or bridge strength & stability.

 Equation of Carr’s Index:

Carr’s compressibility index= (Tap density – Bulk density) ×100

Tap density
OR

(Vt −Vb)
C= ×100 Where
Vt
Vb = Volume occupied by a given mass of powder before tapping,
Vt = Volume occupied by a given mass of powder before tapping

 Hausner’s Ratio:
The ratio sigma max /sigma min is related to interparticulate friction and as such
could be used to predict powder flow properties.
Powder with low interparticulate friction , such as coarse spheres have Hausner’s ratio
of approximately 1.2 whereas more cohesive and less free-flowing powder such as
flakes have Hausner’s ratio greater than 1.6.

 Equation for Haunser’s ratio:

2
 Hausner’s ratio= Tapped density
Bulk density
S

OR
Pt
H=
Pb

Where 
Pb = freely settled bulk density of the powder,
Pt = tapped bulk density of the powder.

Scale of flowability for Carr’s compressibility index and Haunser’s ratio:

Carr’s index Haunser’s ratio Flow ability
5 – 15 1.05 - 1.18 Excellent
12 – 16 1.14 – 1.20 Good
18 – 21 1.22 – 1.26 Fair-possible
23 – 35 1.30 – 1.54 Poor
33 – 38 1.50 – 1.61 Very poor
>40 >1.67 Very- very poor

Both the Hausner’s ratio and the Carr’s index are sometimes criticized, despite their
relationships to flowability being established empirically, as not having a strong theoretical
basis. Use of these measures however persists, because the equipment required to perform the
analysis is relatively cheap and the technique is easy to learn.

Angle of repose:
It is a simple practical technique used for measuring resistance to particle movement. It may
be defined as;
“A maximum angle that can be obtained between the freestanding surface of powder
heap and the horizontal plane.”

 Equation for angle of repose:

2h
tan Φ=
D

3
The fractional and cohesive forces in a powder are reflected with the help of angle of repose.
Since frictional and cohesive forces opposes the gravitational forces acting on particles, the
greater these forces in relation to gravitational forces, the greater will be the Angle of repose.

Methods of determination of Angle of Repose:

Static angle of repose Dynamic angle of repose

Fixed funnel method

Rotating cylinder Tilting box
method method

The different methods may produce different values for same powder,although these may be
self consistent. It is also possible that different angle of reposecould be obtained for the same
powder; owing to the difference in the way the sample was handled prior to the measurement.
For these reasons angle of repose tends to be variable and is not always representative of flow
under specific condition.

Dynamic Angle of repose or Kinetic Angle of repose:

Dynamic angle of repose are preferred because they closely mimics the manufacturing
situation, in which the powder is in motion. With care, dynamic angle of repose
measurements can be replicated with relative standard deviations of approximately 2%.

Tests of dynamic Angle of Repose;

Two tests can be performed for dynamic angle of repose. These are

 Rotating cylinder method;

It is a typical dynamic test in which a hollow cylinder with one end sealed by a
transparent plate, is half-filled with the test powder. After which the cylinder is
rotated about its horizontal axis, until the powder surface cascades.

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 Tilting box method;
A sand-paper lined rectangular box is filled with powder and carefully tilted until the
contents begin to slide. The maximum angle that a plane of powder makes with the
horizontal surface on rotation is taken as the angle of repose.

Flow Properties:

Angle of Repose Flow

Less than 25 Excellent

25-30 Good

30-40 Passable

More than 40 Very poor

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Determination of angle of repose of provided sample (Fixed Funnel Method)
Requirements;

 Graph paper
 Funnel
 Tripod stand
 Spatula
 Sample (Lactose & Mgnesium Stearate)

Procudure;
1. Place a graph paper on a flat horizontal surface.
2. A powder filled funnel is fixed on the graph paper with the help of stand such that the
bottom of orifice is 10cm from bench surface.
3. The outlet is closed and carefully filled to the rim with powder.
4. The contents are now allowed to pour out.
5. The diameter of cone (D) and height of heap (h) is measured.
6. Procedure is repeated by adding 1%, 2% & 3% of glidant in powder.

Limits:
1. If the angle exceeds 50˚, the powder will not flow satisfactorily while materials
having values near the minimum, i-e., 25˚, flow easily and well.
2. Formulation recommendation is required such as granulation
3. Special auger feed is needed
4. Test system is required foe evaluating the improvements in flow brought about by
formulation.

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 Determination of Carr’s Compressibility Index of provided sample of
granules.
Requirements:

 Graduated cylinder
 Sample of granules

Procedure;
1. Take a suitable glass cylinder having rubber base.
2. Carefully load 50g powder ( lactose ) via funnel into tarred cylinder.
3. Record this initial volume (v0 ).
4. Now tap the contents and record the powder volume up to 50 taps ( v50).
5. Calculate the Carr’sCompressibility index using formula.
6. Repeat the whole procedure by adding 1%,2%,3% and glidant in powder.
Uses:

 It is used to determine flowability of granules

 If I = less than 15 % then powder has good flow property
 I = in the range of 15-25% = shows moderate flow
 I = above 25% then flow is poor

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 Determination of Hausner’s ratio from tapped and bulk density
Requiremenst:
 Measuring cylinder
 Weighing balance
 Spatula

Procedure:
1. Take known mass of powder in a measuring cylinder, fill it up to 50ml.
2. Find bulk density of the powder
3. Tap it 50 times and then find the tap density of the powder
4. Find the Hausner’s ratio by the following formula;
Pt
H=
Pb
Where
Pt = Tap density and
Pb = bulk density.
Uses:
It gives information about the compressibility data and flowability characterization for
several drugs and other pharmaceutical exciepients.

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 Determination of Tapped and Bulk Density of powder & determine the
Carr’s Index from the respectives densities
Requirements:

 Measuring cylinder
 Weighing balance

Procedure:
1. Take the known mass of sample in in a measuring cylinder upto 50ml.
2. Find the bulk density of powder by the formula
m
Pb=
Vb
3. Then tap 50 times the cylinder and again find the density that would be the tapped
density using the formula
m
Pt =
Vt
4. Now calculate the Carr’s index by using the following formula
Pt −Pb
C= × 100 %
Pb

Where
C= Carr’s index
Pt = Tap density
Pb= Bulk density

9
 Gel
Definition of gel:
“Gels are the semi-solid system coating dispersion of small or large organic molecule in
an aqueous vehicle rendered jelly like by the addition of gelling agent.”
Gelling agents:

 Cellulose derivatives such as carboxymethylcellulose, hydroxyl propyl methyl

cellulose
 Natural gums such as tragacanth.

Purpose of dosage form:

 Drugs for eye problems that is ophthalmic solution have less residence time on the
surface of eye (hence less absorption) because of rapid removal of tearing and other
natural mechanism. But gels provide extended residence time on the surface of eye,
increasing absorption of drug into ocular tissue.
 Insoluble drugs can be applied in the form of gels
 Used as base for medicated pastilles

Comparison of gel with other dosage forms:

 Gels are better than solution dosage form which are used opthalmically or topically
which remain in contact with skin for a longer period of time.
 Gels are effective as other nasal, rectal, vaginal, creams, and ointments.
 Gels don’t have base but ointments have
 Gels have thixotropic properties but other dosage form haven’t
 Gels have single or two phase system

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 Preparation of Aloe Vera Gel
Ingredients:
 Tragacanth--------------------------- 1g
 Methyl salicylate-------------------- 1g
 Eucalyptol---------------------------- 1ml
 Glycerin------------------------------- 15g
 Purified Water------------------------ 83ml
 Aloe Vera------------------------------10g

Procedure:
1. Cut the aloe-vera plant with the help of knife
2. Clean all the leaves and separate the aloe-vera mucilage from peel
3. Crush the mucilage in patle and mortar
4. Add tragacanth and glycerin in it
5. Mix it
6. Now add remaining ingredients that are methyl salicylates and eucalyptol and mix
them thoroughly
7. Now make up the volume with water
8. Keep the final preparation in close container

Uses:
To treat different skin conditions like cut, edema, burn, inflammation and pain.

Role of ingredients:

Ingredients Uses

Water As solvent or vehicle

Tragacanth As emulsifier, thickener and stabilizer

Methyl salicylate Analgesic, rubefacient

Eucalyptol Anti-inflammatory, Flavoring agent

Glycerin Humectants

Aloe Vera Active ingredient

11
 Drying of Solids
The moisture in a solid is expressed in two ways;

 Wet-weight basis
 Dry-weight basis
On a wet-weight basis, the water content of a material is calculated as the percentage of the
weight of the wet solid, whereas on the dry-weight basis, the water is expressed as a
percentage of the weight of the dry solid.

Loss on Drying:
The term loss on drying is commonly referred as “LOD”. It can be defined as;
An expression of moisture content on a wet-weight basis is called loss on drying (LOD).

 Equation for % LOD;

wt . of water sample
% LOD= ×100
total wt . of wet sample

Moisture Content:
Moisture content commonly referred as “MC”. It can be defined as;
“A measurement of the moisture in a wet solid calculated on the dry-weight basis is
called moisture content (MC).”

 Equation for % MC;

wt . of water ∈sample
% MC = ×100
wt . of dry sample

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 Determination of Loss on Drying (LOD)
Requirements

 Sample of granules
 Weighing balance
 Glass-stoppered bottle
 Pestle and mortar

Procedure:
1. Mix and accurately weigh the substance to be tested and unless otherwise
directed in the Standard test procedure (conduct the determination on 1 to 2 g)
1. If the test specimen is in the form of large crystals, reduce the particle size to
about 2 mm by quickly crushing via pestle and mortar, before weighing out
the test specimen.
2. Tare an appropriate glass-stoppered, shallow weighing bottle that has been
dried for 30 minutes under the same conditions to be employed in the
determination and cooled to room temperature in a desiccator.
3. Put the test specimen in the bottle, replace the cover, and accurately weigh the
bottle and the contents.
4. By gentle, sidewise shaking, distribute the test specimen as evenly as
practicable to a depth of about 5mm generally and not more than 10mm in the
case of bulky materials.
5. Place the loaded bottle in the drying chamber, removing the stopper and
leaving it also in the chamber.
6. Dry the test specimen at the temperature and for the time specified in the
monograph by one of the following procedures (Note: The temperature
specified in the monograph is to be regarded as being within the range of ±
2°C of the stated figure):
7. Upon opening the chamber, close the bottle promptly, and allow it to come to
room temperature in a desiccator before weighing.
8. Where drying in vacuum over a desiccant is directed in the Standard test
procedure, a vacuum desiccators or a vacuum drying pistol, or other suitable
vacuum drying apparatus, is to be used.
9. Where drying in desiccator is specified, exercise particular care to ensure that
the desiccant is kept fully effective by frequent replacement.
10. Weigh the sample.
11. Calculate the %LOD
wt . of moisture
% LOD= ×100
wt . of sample

LOD limit:

 0% > to < 100%

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 Determination of Moisture Content (MC)
Requirements

 Sample of granules
 Electric balance

Procedure:
1. Weigh accurately the provided sample of granules on balance.
2. Heated the sample for one hour in oven
3. Cool the sample at room temperature.
4. Weigh the sample.
5. Calculate the %MC.
wt . of moisture
% MC = ×100
wt . of dry sample

MC limit:

 0% > to ∞

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 Particle Size Distribution
For the analysis of particle size, numerous methods are use that are varying in principle.
Generally the term particle size can be defined as;
“A Particle size of less than 1000 µm however practiclay it may be defined as particles
with a mean diameter of 20 µm to 1000 µm.
Particle size determination;
The particle size distribution in a powder may be quantified by;
1. Determining the number of particles microscopically
2. Determination via the particles weight such as sieving, sedimentation,
centrifugation e.t.c
3. Determining the volume of particles such as coulter counter method and
4. Determining the light scattering by particles such as UV, FT-IR and laser
light scaterring techniques.

Sieving
“A simple ‘technique that divides the powder into two fractions one above and other
below a specified size”
In this process the powder is passed over a perforated screen/mesh so that particles
sufficiently small will pass through it, while oversized particles will be retained on the
sieve.To obtain a distribution of particle size, number of sieves of different mesh size are
mounted together in such a way that coarsest particles are retained on the top sieve while
finest at the bottom.
Advantages;
1. In-expensive
2. Simple
3. Rapid with variation between operators
Limitations:
1. Particles can be attracted electrostatically to form aggragates
2. Humidity canm affect the particles of hygroscopic materials
3. Particle shape greatly affect the sieving process
4. Standardization of technique is essential

Milling:
Milling can be defined as
“The reduction of materials to smaller pieces, to coarse particles, or to powder is called
milling”
Raw materials are too large in size, so they must be reduced into smaller sizes, for this
purpose milling is used.

15
Types of milling;
Size-reduction operation or milling is divided into two main categories depending upon the
material.
1. For solid material--- grinding and cutting
2. For liquid material---- emulsification or atomization

Milling, grinding and cutting reduce the size of solid materials by mechanical action i-e., by
fracturing them. The material is stressed by the action of mechanical moving parts in the
milling machine and initially the stress is absorbed internally by the materials as strain
energy. When the local strain energy exceeds a critical level (yield point), fracture occurs
along lines of weakness and the stored energy is released.
Milling is therefore, achieved by mechanical stress followed by rupture and the energy
required depends upon the hardness of the material and also upon the tendency of the
material to crack.
Stress-Strain diagram;

 The initial linear portion of the curve is defined by Hooke’s law and Young’s
modulus expresses the stiffness or softness of a solid in dynes per suare centimeter.
 The stress-strain curve becomes non-linear at a yield point, which is the measure of
resistance to permanent deformation.
 With still greater stress the region of irreversible plastic deformation is reached.
 The area under the curve represents the energy of fracture and it is the approximate
measure of the impact strength of the material.
Energy for grinding:
Fine grinding requires more energy, not only because of the increased new surface, but also
because more energy is needed to initiate cracks. That means size reduction begins with the

16
opening of any small cracks that were initially present. Thus, larger particles with numerous
cracks fracture more readily than smaller particles with fewer cracks.
Mostly efficient mills utilizes less than 1% of the energy to fracture particles. The rest of the
energy is dissipated in;
1. Elastic deformation of unfractured particles
2. Tranportation of material
3. Friction
4. Heat
5. Vibration and noise
Force of impact:
If a force of impact does not exceed the elastic limit, the material is reversibly deformed or
stressed. When the force is removed, the particles returns to its original form, and the
mechanical energy of stress in the deformed particle appears as heat.
While on the other hand a force that exceeds the elastic limit fractures the particles, Usually,
the surface of the particles are irregular, so that the force is initially taken on the high portion
of the surface.
As fracture occurs, the points of application of the force are shifted. The energy of the new
surfaces is partially supplied by the release of stress energy.Crystalline materials fracture
along crystal cleavage planes, and non-crstalline materials fracture at random.

Mill:
Milling involves the application of mechanical energy to physically break down coarse
particles to finer ones, the infrastructure that perform milling is called mill.

Types of mills
There are many types of mills, some of them are;

 Rotary cutter mill

 Hammer mill
 Ball Mill
 Roller mill
 Fluid-energy mill
 Colloid mill

17
Ball Mill:
Construction and Running of Ball Mill:
The ball mill consists of a horizontal rotating hollow vessel of cylinder shape with the length
slightly greater than its diameter. The mill is partly filled with balls of steel hence called ball
mill.

Schemic Representation of Ball mill

Continuous ball mills are fed through a hollow trunnion (cylindrical extension) at one end,
with the product discharge through a similar trunnion at the opposite end. The outlet is
covered with coarse screen to prevent the loss of the balls.

18
Principle of Ball Mill:
The working principle of ball bill is simple,i-e.,;
“Impact and attrition size reduction take place combinely as the ball drops from near
the top of a rotating hollow cylindrical shell”, it is a type of grinder used to grind & blend
bulk materials into smaller particles using different sizes of balls (however smaller balls give
a slower but a finer grinding).

Modification of Ball Mill:

Ball mill can be modified by replacing the ball with some other material or by changing the
size of the mill. Following are the modifications of the ball mill;

 Pebble mill
 Rod mill
 Tube mill
 Conoical ball mill
 Small-scale vibration ball mill

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 Determination of particle size distribution of provided sample of granules
Requirements;

 Different sizes of sieves 16, 20, 60, 250

 Weighing balance
 Provided sample.

Procedure;
1. Set the slandered sieves in such a way that the coarsest sieve is on the top and the
finest sieve is at the bottom.
2. Accurately weigh the given powder and passed it through the sieve.
3. Then passed the leftover quantity through the next sieve and so on.
4. Weight the quantities of powder passes over through different sieves.
5. Calculate the percentage of size distribution by applying the following formula;
passed
¿ weight of material sieves
different
% ×100
Total weight of the powder

Plot % weight size distribution the amount of powder retained on each sieve against the sieve
number.
Limitations:
1. Particles can be attracted electrostatically to form aggragates
2. Humidity canm affect the particles of hygroscopic materials
3. Particle shape greatly affect the sieving process
4. Standardization of technique is essential

20
 Crushing of the given sample with the help of Ball Mill.
Requirements:
 Given sample
 Ball Mill
 Balls
 Sieve

Procedure:
1. Clean the balls and mill from inside.
2. Put the balls and given sample in the cylinder
3. Start the machine, after sometime check the material, if it needs further particle size
reduction restart machine.
4. When the material is reduced, it is taken out from vessel and pass through sieve inder
to get desired size.

Applications:
1. Can be use for batch or continuous process
2. Can be used for sterile milling in the production of ophthalmic and parenteral
products
3. Cheap to use
4. First choice for fine grinding hard and abrasive material.

21
 Operation of Silverson Mixer
Fluid emulsions are prepared by means of a shrouded turbine such as Silver son Mixer
emulsifier. Models are available for batch processing quantities from a few milliliters up to
several thousand liters while continuous processing can be achieved by incorporation into a
pipeline.
An international company, Silverson is represented by a network of associated companies,
distributors and agents in over 50 countries, serving North America, Europe, Asia,
Australasia, South America and Africa.
The sliver son homogenizer works on the principle that the large globules in a coarse
emulsion are broken into smaller globule by passing them under pressure through a narrow
orifice.

CONSTRUCTION
 It consists of a emulsifier head which is covered with the fine meshed stainless steel sieve.
 The emulsifier head consist of a number of blades which rotates at high speed in order
to produce a powerful shearing action.
 The blades are rotated by using the electric motor fitted at the top.

WORKING
 The emulsifier head is placed in the vessel containing immiscible liquids, in such a
way that it should get dipped into it.
 When the motor is started, the liquids are sucked through the fine holed and the oil is
reduced into the globules due to the rotation of the blades.
 The precision machined Silverson work head generates exceptionally high shear rates
in a four stage mixing/homogenizing process:

PHARMACETICAL APPLICATIONS
 It is used for most products, including creams, ointments, sauces, flavoring emulsions
and pharmaceutical suspensions, this requires a globule or droplet size in the range of
2-5 microns. This can be achieved using a Silverson Mixer Homogenizer.
 Silverson Mixer Homogenizers are fast and efficient and are capable of producing a
fine droplet or particle size, typically in the range of 2-5 microns.
The Columns support the head in which turbine blades are driven. These are powered by a
motor above the supporting columns which act via the drive. Centrifugal forces expel the
contents of the head through the mesh when large shearing and impaction forces produce a
fine emulsion which emerges from the openings. Circulation of material through the head is
maintained by the suction produced in the inlet at the bottom of the head.

22
 Tablet Compression Machines (Tablet Presses)
Introduction:
Tablet Compression Machines are also called as Tablet Presses. Tablets are made by
compressing a formulation on presses (stamping machines). These are used for compressing
granules and powders.

Types of Tablet Presses:

Depending upon the stations in which compression occurs, tablet presses are classified as;
1. Single-Punch Machine
2. Multi-Staion Rotary Presses

Single-Punch Machine:
Single punch tablet press also called eccentric press or single station press is the simplest
machine for tablet manufacturing.All of the compression in single-punch machine is applied
by the upper punch, making it “stamping press”. The single punch tablet press produce about
60-85 tablets/min.

23
Working:
The events involved in tablet production via single-punch machine can be divided into 3
stages;
1. Filling
2. Compression
3. Ejection

 Filing:
Position 1 – The upper punch is raised and lower punch drops to create a cavity in the
die.
Position 2 – Feed shoe moves over the die cavity and granules fall into the die cavity
under the influence of gravity from the hopper.
 Compression:
Position 3 – Feed shoe moves out of the way and the hopper punch descends to
compress the granules/powder mixture into tablets by progressive reduction of the
porosity of the die content and forcing of the particles into close contact with one
another.
 Ejection:
Position 4 – The upper punch retracts and the lower punch moves upwards too to
eject the compressed tablet. The whole events repeat over and over again unit the feed
material is exhausted.

Movement involved in compression

24
Compression Cycle:
The compression cycle of a single-punch tablet press follows the following order;
1. Feed shoe over die
2. Fill
3. Feed shoe back
4. Compression
5. Ejection

Cross-Section of single pumch machine showing compression cycle

Multi-Staion Rotary Press:

Rotary tablet press is a mechanical device that has several tooling station which rotates to
compress granules/powder mixture into tablets of uniform size, shape (depending on the
punch design) and uniform weight. It was developed to increase the output of tablets. In
rotary tablet press, the compaction force on the fill material is exerted by both the upper and
lower punches leaving the powder granules to be compressed in the middle. This is known as
accordion type of compression.  The capacity of a rotary tablet press is determined by the
rotation speed of the turrent and the number of stations on the press.

Contruction:
The multi- rotary press is composed of the following parts;
1. Hopper
2. Die cavity
3. Feed paddle
4. Punches
5. Lower can track
6. Camp tracks
7. Dept of fill
8. Recompression rollers
9. Main Compression
25
 10. Ejection cam
11. Take off blade
12. Discharge chute

Working:
The rotary tableting machine follows the following stages to compress the tablets;

1. Filling Stage
2. Compression stage
3. Ejection Stage
Advantages of Rotary Tablet Press (Multi-station tablet press):
 High productivity can be gained with a minimal amount of labour while saving
money.
 Rotary press has an output of between 9000 – 234000 tab/hour thus saves time and
meets up with the high demand of tablet dosage form.
 The powder filled cavity can be automatically managed by a moving feeder.
 Rotary press decreases waste of valuable formulation in non-specific tablets.
 The machine allows independent control of both weight and hardness.

26
 To study different parts of single punch tableting machine (Tablet
Compression Machine)
Parts of Single-Punch Machine:
1. Hopper;
It holds the granules in position for the compression
2. Feed shoe;
Present over die, it is used for moving granules into the die
3. Dies;
They gives the shape and size to tablets
4. Punches;
Pair of punches are present i-e., upper and lower punches, used for compressing the
granules within the dies
5. Cam tracks;
They shows the way to punches for the movement

Advantages of Single Punch Tablet Press:

 The single punch structure is rational and small.
 Easy to operate and it operates at a high utilization ratio.
 It can manufacture odd shaped products with a diameter of up to 20mm.
 It is ideal for development of tablets and small batch production.
 Single punch tablet press utilizes a high amount of pressure to reduce weight
variations between tablets while maintaining a low noise level at the same time.

27
 Operation of oscillating granulator

Application & Process:

Oscillating granulator is used for gentle homogenization, size reduction, grading and sieving
of dry, sensitive powders and granules in pharmaceutical, chemical and food industries.

Oscillating Granulator has one rotor with five edges, which oscillate on horizontal axis at
about 180 per minutes. There is one half round sieve mounted at the bottom of the rotor.

There is one half round sieve mounted at the bottom of the rotor.

Product is charged from the top through in feed hopper and material falls on the rotor lades.
The particles are broken by a set of oscillating bars arranged in cylindrical form over a screen
of suitable mesh. Due to the sharp edges on rotor, the downsizing of particle takes place and
through sieve material gets pushed outward from the bottom opening.

The oscillating motion of the rotor improves the granulating process. The important feature of
the oscillating granulator is the continuous force and speed applied to the material. The back
and forth motion of the rotor results in an even distribution of the material

28
 Manufacturing of Granulation (For Tableting)
Granulation:
“The process of formation of granules from powder sample is known as granulation”

Tableting:
“Any of the procedures used to compress a powder formulation into a solid tablet form is
called tableting.”

Methods of Manufacture of Granulation:

Manufacture of granulation for tableting is done via 2 methods i-e.,
1. Dry Method
a. Direct Compression
b. Compression Granulation
2. Wet Method.

Processing steps required in various Tablet Granulation Preparation Techniques

Dry Manufacturing Methods (Dry Granulation)

“Dry granulation is the process of forming particles i.e., granulates or granules from dry
powder or powder blend without adding liquid to aid in the process”

Methods of dry granulation:

Dry granulation method is mainly divided as follows;
Dry Method

Direct Compression Compression Granulation

Slugging Method Roller Compaction

Method 29
 1. Direct Compression:
“The term ‘direct compression’ is defined as the process by which tablets are compressed
directly from powder mixture of ‘Active pharmaceutical ingredient’ & suitable excipients.”
In this method the active ingredients & exciepients are weighted, mixed and then compressed
directly into the tablet by tableting machine.

Examples:
There are few crystalline substances that are directly compressed, such as;
1. Sodium chloride
2. Sodium bromide
3. Potassium chloride

Advantages of Direct Compression:

1. High bioavailable drugs
2. Cheap
3. Very few stability problems

Disadvantages of Direct Compression:

1. It may generate a lot of dust
2. More chances of segregation, if API & exciepients have variable densities
3. Few compounds can only be compressed

2. Compression Granulation:
Dry granulation uses mechanical compression (slugs) or compaction (roller compaction) to
facilitate the agglomeration of dry powder particles. That’s why compression granulation is
further divided as;

Compression Granulation

Small-Scale Method Large Scale Method

Roller Compaction
Slugging Technique
Method

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Slugging Technique:
When the initial blend of powders is forced into the dies of a large capacity tablet press and
is compacted by means of flat-faced punches, the compacted masses are called “slugs” and
the process is referred to as “slugging”.
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.
Factors effecting;
Factors which determine how well a material may slug includes;
1. Compressibility or cohesiveness of the mater
2. Compression ratio of powder
3. Density of the powder
4. Machine type
5. Punch and die size
6. Slug thickness
7. Speed of compression
8. Pressure used to produce slug

Advantages
1. For moisture sensitive material
2. For heat sensitive material
3. For improved disintegration since powder particles are not bonded together by a
binder

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Roller Compaction:
On large scale, compression granulation can also be performed on a specially assigned
machine “roller compactor”. Technically it s also called as “chilsonator”

Schemic diagram of a Chilsonator roller compactor

The compaction force of the roller compactor is controlled by three variables;

1. The hydraulic pressure exerted on the compaction rolls
2. The rotational speed of the compact rollers
3. The rotational speed of the feed screws
Advantages of Compression Granulation:
1. Valuable technique in which the effective dose of a drug is too high for direct
compression
2. Requires less equipments and space
3. The process eliminates the addition of moisture and allows dry handling of
moisture sensitive formulation ingredients.
4. The process is suitable for heat sensitive materials since no drying step is
involved.
5. Dry granulation is not generally associated with alterations in drug morphology
during formulation process.
6. The process does not require special excipients that is, it makes use of
conventional grades of excipients.
7. Tablets manufactured by dry granulation method have improved disintegration
time because the dry binder used has less adhesive effect thus fast disintegration.
8. The process is easily scaled up from development to production.
9. It improves blending since there is no migration.

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 Disadvantages of Compression Granulation
1. Dry granulation method (roller compaction) require specialized heavy duty equipment for
granulation.
2. The process generates considerable dust which may cause cross contamination.
3. Segregation of components may occur post mixing.
4. There may be issues regarding powder flow.
5. Tablets manufactured by dry granulation tend to be softer than those manufactured by wet
granulation, rendering them more difficult to process using post-tabletting techniques,
e.g. film coating.

Wet Manufacturing Method (Wet Granulation)

“The massing of a mix of dry primary powder particles using a granulating fluid is called
wet granulation”
Wet or moist granulation is the most widely used method in tablet preparation.This method
involves both moistuning as well as drying of the material. It uses adhesive or granulating
agent to produce a granular product, which has improved flow properties and has ability to
cohere under pressure.

1. Wetting & Nucleation 2. Coalescence or ball growth 3. Consolidation 4. Attrition or breakage.

Advantages of wet granulation:

1. Wet granulation modifies the properties of formulation ingredients to overcome their
tableting deficiencies.
2. Granules formed are relatively more spherical than the powders and have better flow
properties.
3. Improved compressibility of powders resulting from wet granulation process allows
the use of low pressure during compression. This reduces machine wear and thus
improves the life of the machine.
4. The process makes use of conventional excipients and therefore is not dependent on
the inclusion of special grades of excipients.
5. It ensures better content uniformity, especially for soluble low-dose drugs.

33
 6. The process may improve the dissolution rate of poorly soluble drugs by imparting
hydrophilic properties to the surface of the granules.
7. Wet granulation prevents segregation of components of a homogenous powder mix
during processing.
8. Wet granulation reduces the level of dust present during manufacturing process
thereby reducing the incidence of cross-contamination and risk to workers.
9. Wet granulation reduces the amount of air entrapment thereby increasing powder
compressibility.
Differences between wet granulation and dry granulation methods
1. Typically, wet granulation processes require more equipment and plant space than dry
granulation technology.
2. Wet granulation technology makes use of multiple and more expensive equipment
technology; thus has higher investment costs compared with dry granulation processes.
3. Cleaning cycles are more frequent with wet granulation equipment trains than dry granulation
manufacturing equipment.
4. Scale-up is less complicated with dry granulation compared with wet granulation.
 Wet granulation scale-up has many more major and minor variables to monitor during wet
granulation and drying processes than a dry granulation roller compaction process.
 Scale-up using wet granulation equipment requires larger bowl and batch sizes—
manufacturing capacity is a function of bowl size volume and manufacturing time.
 Scale-up using roller compaction can be accomplished with development sized equipment—it
only requires longer equipment operating hours as manufacturing capacity is primarily a
function of operating time providing more capacity and operational flexibility.
5. Wet granulation endpoints can change as the granulator power consumption profile can
change when manufacturing multiple consecutive batches during a shift or campaign-
requiring more sensor controls to understand the process.
6. The wetting of raw material is more influenced by raw material property changes, for
example, particle size distribution, and density than raw material changes affecting roller
compaction.
7. In the case of manufacturing a wet granulation batch, if an electrical outage occurs, the
probability of losing the batch is high if there is no backup battery system to quickly start up
and continue the process; this is not an issue with a roller compaction process.
8. Massing effects and drying capacity issues are key concerns in scale-up for drying
granulations produced in separate steps for high- or low-shear wet granulation technologies.

34
 Manufacturing of Tablets by Direct Compression Method
Ingredients Master Formula Working Formula
 Starch------------------------------0.300kg
 Lactose----------------------------12.870kg
 Maize Starch----------------------0.700kg
 Sodium Benzoate----------------0.20kg
 Avicel 101------------------------4.430kg
 Magnesium Stearate-------------0.130kg
 Talc--------------------------------0.376kg
Bulk Quantity: 19kg
Weight of 1 Tablet: 190mg

Procedure:
1. Pass the Avicel 101 and Lactose through sieve # 40 and mix well for 10 minutes in
Ribbon Mixer.
2. Make Starch paste by dissolving Maize Starch in 3.75 liter of deionized water. Add
Sodium Benzoate in paste and mix well in SS vessel with SS spoon until a uniform paste
is produced. Add this paste to (I) in portions and knead well (for 12 minutes) till uniform
wetting. Pass from sieve (mesh # 10), Dry at 400C in tray dryer.
3. Weigh the dried granules and pass from oscillating Granulator (mesh #12).
4. Pass starch, Talc and Magnesium Stearate from sieve # 10 and granules from sieve # 10
and mix.
5. Mix all for 10 minutes in Cone mixer.
6. Transfer to the compression section in SS. container.
7. Compress into tablets and check for in process tests.
8. Proceed for compression if tablets are O.K.

Limitations:
1. Direct compression is more prone to segregation due to the difference in density of the
API and excipients. The dry state of the material during mixing may induce static charge
and lead to segregation. This may lead to the problems like weight variation and content
uniformity.
2. Expensive method

35
 Manufacturing of tablet by Dry granulation method (Small-scale)
Requirements:
 Single punch machine
 Oscillating granulator

Procedure:
The various steps used in the manufacture of tablets by dry granulation method are:

1. Weighing formulation ingredients;

First the 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;

The dispensed formulation ingredients are mixed in a powder mixer until a uniform powder
mix is achieved. Then 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;
In the next step the mixed ingredients are compressed into flat large tablets or pallets. This
step is called precompression (slugging) and the compacts made in the process (typically 25
mm diameter by about 10–15 mm thick) are termed slugs.
4. Milling and sieving of slugs;
After 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 extragranular 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;
The mixed granules are compressed into tablets using either single or rotary tablet press fitted
with appropriate punches and dies.
Limitations:
1. It requires a specialized heavy duty tablet press to form slug
2. It does not permit uniform colour distribution as can be achieved with wet granulation
3. The process tends to create more dust than wet granulation.

Preparation of granules from powders by wet granulation method

Steps & Procedure:
Steps involved

36
Step 1: Weighing and mixing of formulation ingredients (excluding the lubricant).
Step 2: Preparing the damp mass
Step 3: Wet screening/ Screening the dampened powder into pellets or granules
Step 4: Drying of moist granules
Step 5: Sizing the granulation by dry screening
Step 6: Lubrication of granules
Step 7: Compression of granules into tablets
Follow the above steps for the following procedure;
Add starch in water and heat until mass of uniform consistency is achieved. Cool and add to
lactose and knead well, then pass through sieve number 10. And dry the mass in hot air oven
at temperature not exceeding 60°C. After drying, pass through sieve#10 for uniform sizing of
granules.

Limitations:
1. Wet granulation often requires several processing steps.
2. The cost of wet granulation is higher because of the time, labour, energy, equipment and
space required for the process.
3. The process is not suitable for thermolabile and moisture-sensitive materials.

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 Preparation of Ascorbic acid tablets by wet granulation method
Requirements:
 Ascorbic acid----------------------10g
 Lactose-----------------------------4.2g
 Starch-------------------------------3.2g
 CMC (2%)-------------------------As required
 Talcum-----------------------------0.2g
 Ca. Stearate------------------------0.2g
Procedure:
10. Triturate ascorbic acid and Lactose together by using pestle and mortar. After mixing, add
CMC solution, until a tough mass is formed.
11. Then pass this mass through sieve #10 and dry.
12. Then mix starch, talc and calcium stearate with these granules and compress under the
standard concave punches.

Uses:
1. Treating and preventing low levels of vitamin C.
2. Doses of 25-75 mg are sufficient to prevent vitamin C deficiency.

Role of ingredients:

Ingredients Uses

Ascorbic acid Active Ingredient

Lactose Diluent

Starch Disintegrant

CMC (2%) Binding agent

Talcum Glident

Calcium Stearate Lubricant

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 Preparation of Effervescent Granule
Granules
Granules are particles ranging in size from about 4 to 10 mesh, they are defined as;
“A dosage form composed of dry aggregates of powder particles that may contain one or
more APIs, with or without other ingredients are called granules.”
They may be swallowed as such, dispersed in food, or dissolved in water. . generally are
made by first blending the powders together and then moistening the mixture to form a pasty
mass. The mass is pass ed through a sieve and then dried in air or in an oven.
Preparation of Effervescent Granulation
Effervescent salts have classically been used to disperse medicines in water for oral
administration. Effervescent salts are granules or coarse powders containing a medicinal
agent in a dry mixture, usually composed of sodium bicarbonate, citric acid and tartaric acid.
When the salts are added to water, the acids and the base react to liberate carbon dioxide gas,
thereby causing "effervescence". The resultant carbonated solution masks the usually saline
or otherwise undesirable taste of the medicinal agent present. By using granules or coarse
particles, rather than fine powder, the contact area of the substances is decreased, and the
otherwise violent reaction and rapid uncontrollable effervescence is eliminated. The two
required ingredients are at least one acid and at least one base. The base must release carbon
dioxide upon reaction with the acid.

Advantages of Liberated CO2:

The liberated carbon dioxide has the following advantages :
It masks
 The bitter and nauseous taste.
 It promotes gastric secretions.
 It acts as a carminative.

Methods of preparation:
There are two methods of preparation of granules:
1. Dry fusion method
2. Wet method
1. Fusion method
In the fusion, the one molecule of water present in each molecule of citric acid acts as the
binding agent for the powder mixture.
1 After weighing the required amount of powders they are mixed together to ensure the
uniformity of the mixture.
2 Then the powder is placed on a porcelain dish on boiling water bath and stirred with the
help of a glass rod.

39
3 The heat causes the release of the water of crystallization from the citric acid which in turn
dissolves a portion of the powder mixture, setting of the chemical reaction and the
consequent release of some carbon dioxide.
4 This causes the softened mass of powder to become somewhat spongy, when of the proper
consistency as bread dough ,it is removed from the oven
5 Then rubbed through an acid resistant sieve to produce granules
6 These are then dried at temperature not more than 54 – 60˚ C and transferred to containers
which are then promptly and tightly sealed.

Advantage:
The fused method is used in the preparation of most commercial effervescent powder
2. Wet Method:
1 All powders are dried to constant wt. At temp. 100-105oC.
2 Pulverize each powder through sieve No.90 weigh the calculated amount separately.
3 Pass the pulverized powder through sieve No. 90 and weigh the calculated amount from
each powder separately .
4 Mix the powder together and by the aid of alcohol 96 % ( drop adding ) make the mass
coherent between your fingers and the mixing is continued until the mass will retain its shape
when molded into a ball.
5 The mass is forced through sieve No. 10 then dry in ovens at temp. not exceeding 50oC .
6 After drying the granules sieved through sieve No. 20 to leave the fine particles, and packed
in well closed wide mouth bottles.

40
 Preparation of Effervescent Sodium Citra tartarate granules
Prepare 25 g of effervescent sodium citra tartarate ( B.P.C.) having the following formula:

Requirements:
Sodium bicarbonate……………..510 g
Tartaric acid ……………………270 g
Citric acid……………………….180 g
Sucrose ……………………….150 g
1110 g
These amounts of the ingredient base will give 1000 g only , thus 110 g which is lost due to
liberated CO2& H2O ( chemical loss).

Procedure:
Fusion Method;
1. Before mixing the powders, the citric acid crystals are powdered and then mixed with the
other powders of the same sieve size to ensure uniformity of the mixture.
2. The sieves and the mixing equipment should be made of stainless steel or other material
resistant to the effect of the acids.
3. The mixing of the powders is performed as rapidly as is practical, preferably in an
environment of low humidity to avoid absorption of moisture and a premature chemical
reaction.
4. After mixing, the powder is placed on a suitable dish in an oven at 34ᵒC to 40ᵒC.
5. During the heating process, an acid resistant spatula is used to turn the powder.
6. The heat releases the water of crystallization from the citric acid, which, in turn, dissolves
a portion of the powder mixture, setting the chemical reaction and consequently releasing
some carbon dioxide, this causes the softened mass of powder to become somewhat
spongy
7. When it reaches the proper consistency (as bread dough), it is removed from the oven and
rubbed through a sieve to produce granules of the desired size (A No. 4 sieve produces
large granules, a No. 8 sieve prepares medium size granules, and a No. 10 sieve prepares
small granules.)
8. The granules are dried at a temperature not exceeding 54ᵒ C and are immediately placed
in containers and tightly sealed.
Wet Method;
The wet method differs from the fusion method in that the source of binding agent is not the
water of crystallization from the citric acid but the water added to alcohol as the moistening
agent, forming the pliable mass for granu lation. In this method, all of the powders may be
anhydrous as long as water is added to the moistening liquid. Just enough liquid is added (in
portions) to prepare a mass of proper consistency; then the granules are prepared and dried in
the same manner a s previously described.

41
Uses:
1. Digestive
2. Carminative

42
 Tablet Coating
Tablet coating is the outer covering of a tablet with a layer/substance. It is the last critical
step in the tablet production step.It is the phenomenon of application of coating to the tablet.

Objectives of Tablet Coating:

1. Mask the odour, taste or colour of the drug
2. Provides physical and chemical protection for drug.
3. Controls the release of drug from the tablet.
4. Protects the drug from gastric environment of stomach in case of acid sensitive drug.
5. Avoids chemical incompatibility.
6. Improves pharmaceutical elegance by using colours, and contrasting printers.

Components considered in tablet coating:

1. Tablet Properties: Shape, tolerance, Surface area
2. Coating process:
a.Coating equipment
b. Coating parameters
c. Facility & ancillary equipment
d. automation of coating process
3. Coating composition: polymers, colour, plasticizer, solvent.

Types of Tablet Coating:

The types of coats depending on the specific functionality of the tablet as well as the target
consumer of the tablet.
1. Sugar Coated Tablets
2. Film Coated Tablets
3. Gelatin Coated Tablets
4. Enteric Coated Tablets
5. Compression Coating Tablets
6. Other Types

Applications:
1. Enhance specific functionality
2. Obscure the bitter taste of the tablets
3. Creats a smooth covering to promote easy swallowing
4. Protect the pill from damage or external forces
5. Create a branded pill for marketing purposes
6. Increase the shelf life of the tablets.

43
 Coating of tablets
Formula for coating solution:
Ingredients Master Formula Working Formula
Batch size------------------------------------------------------ 9Kg
HPMCES (Hydroxy propyl methyl cellulose)------------300gm
Methylene chloride-------------------------------------------6.7L
IPA (Isopropyl alcohol0-------------------------------------2.5L
Titanium dioxide---------------------------------------------250gm
PEG 6000 (Polyethylene glycol)---------------------------50gm
Colour----------------------------------------------------------31gm

Procedure:
1. Make coating solution by dispersing HPMCE5 and Titanium dioxide and color in the
mixture of Methylene chloride and IPA.
2. Mix the solution for 45 minutes and filter through coarse cloth.
3. Proceed for coating.
4. Polish tablets with PEG 6000 in the polisher.

Limitations:
1. Increase cost of enery and labor
2. Increase use and cost of organic solvents
3. Specific environment is required

44
 Operation of manual/hand operated capsule filling machine
Requirements;
 Empty hard gelatin capsule shells
 Hand operated capsule filling machine.

Basic principle;
1. Removal of caps
2. Filling of bodies
3. Replacement of caps
4. Ejection of filled capsules
Working
1. In hand operated machine, there is a base plate or perforated disc. In which the empty
bodies of capsules are packed manually.
2. The caps are removed and replaced mechanically.
3. A perforated tray above the body holder is uniformly filled with the powder by means of
spreader.
4. This tray holds the powder over the empty bodies.
5. After this the powder is poured into the empty bodies from the perforated tray and
temper(cushion) plate with rubber pad is used to pack the capsules.
6. When the bodies are completely filled the powder tray is removed and the plate on which
the caps were fitted is replaced on it.
7. The tray is then removed and the capsules are collected.

Limitations:
1. Increase in labor, to produce capsules.
2. More room for human error.
3. Variations in the amount of fill material in each capsule may occur.
4. Limited production capacity, this can make it difficult for you to grow with it as your
business and production demand growth.
5. Heavy weight which can cause great inconvenience for installation, cleaning, and
maintenance.

45
 To calculate percentage limits

A. e,g. if limit is ±5%

Single Upper Limit is =110× 130. /100=SUL=143
Single Upper Limit=90×130 /100=SLL=117
Double Upper Limit= 120 × 130. /100=DUL=156
Double Lower Limit=80 × 130. /100=DLL=104

B. Calculator method
UL= Average wt. Press + key enter required value of percentage press %
key
LL= Average wt. Press ̶ key enter required value of percentage press %
key

Average weight × Required limit

C. =%value
100
Upper Limit (UL) = Average wt. + % value
Lower Limit (LL) =Average wt. ̶ %value

D. Calculate average wt. of tablets.

Average wt. = W
Weight of single tablet from tablet# 1 to tablet# 20 =W1-W20
W −W 1
Now calculate percent difference for every single tablet = × 100
W

And check the limits that weather the variation falls within the limit or not.

46
 Weight Variation
“The variation of weight of tablets/ capsules within the batch or between the batch is called
weight variation”

Tablet Weight Variation:

USP terms this control as weight variation and lists different average weight of tablets against
the permitted deviation as percentage of the average weight.The permitted percentage
deviation decreases with increasing size of tablet or injection weight.

Average wt. of tablet, mg Percentage Difference (%)

130 mg or less ±10

130 through 324 7.5

More than 324 5

Table 1. Weight variation Tolerance for Uncoated tablets, Film coated

tablets and Coated Tablets (tablets other than film coated )

Permitted deviation for 18 Permitted deviation for 2

Average wt. of tablets
of 20 tablets of 20 tablets.

80 mg or less ±10% ±15%

80-250 mg ±7.55% ±12.55%

250 mg or more ±5% ±10.5%

Determination factor & Causes:

The weight of compressed tablets is determined by amount of granulation present in the die
prior to compression, so, any factor that can alters die-filling process can cause alter tablet
weight. Generally there are 2 main causes of weight variation, i-e.,
A. Formulation Causes
B. Machine Causes

47
 To determine weight variation of Uncoated Tablets according to USP
Requirements:
 Tablets
 Weighing balance
Procedure:
1. Uncoated and film coated tablets
Weigh individually 20 whole tablets, and calculate the average weight. The requirements are
met if the weights of not more than 2 of the tablets differ from that average weight by more
than the percentage listed in the accompanying table and no tablet differ in weight by more
than double that percentage.
Note; the same range of percentage deviations for the stated weight for pro-injections is
allowed as for tablets.
2. Coated tablets (other than film-coated tablets)
Weight individually 20 whole tablets, and calculate the average. If the coated tablets do not
conform to the criteria in the accompanying table, place 20 tablets in a beaker of water at
37oC and swirl gently for not more than 5 minutes. Examine the cores for evidence of
disintegration and repeat the procedure for a shorter time if disintegration has begun. Dry the
cores at 50oC for 30 minutes. Accurately weigh 20 individual tablet cores, and calculate the
average weight.
The requirements are met if the weights of not more than 2 of the tablets differ from the
average weight by more than the percentage listed in the accompanying table and no tablet
differs in weight by more than double the percentage.

Caution:
1. The weights of at least 18 of the 20 tablets examined must fall within the permitted
deviation limits.
2. The weight of the remaining two tablets must not deviate from the average by more
than the percentage deviation indicated in the table.
3. It is permissible, if twenty tablets are not available to examine, only ten, not less
than nine must be within the permitted deviation from the average weight, one
may deviate by not more than the permitted deviation indicated USP

48
 Uniformity of weight for capsules
Capsules comply with the following requirements, using method A for capsules for dry
contents and method B for capsules containing a liquid or paste.

Method A:
Weigh a capsules, open it without loss of shell material, remove the contents and weigh all
parts of shell. The difference between the weights represents the weight of contents. Repeat
the operation with a further nineteen capsules and calculate the average weight of the
contents of twenty capsules. The weight of contents of each capsule does not deviate from the
average weight by a greater percentage then that shown in the column A of the table, except
that for two capsules, the weight of the contents may deviate by not more than the percentage
shown in the column B.

Method B:
Weigh a capsule, open it without loss of shell material, express as much of the material as
possible, wash the shell with solvent ether, reject the washings, allow the shell to stand until
the odour of ether is no longer perceptible, and weigh. The difference between the weights
represents the weight of the contents. Repeat the operation with a further nine capsules and
calculate the average weight of the contents of ten capsules. The weight of the contents of
each capsule does not differ from the average weight by more than 7.5%, except that for one
capsule. The weight of the contents may differ by not more than 15%. Regardless of the
weight of contents in this type of capsules, the percentage deviation ranges between ±7.5 to
±15% (BP 2009)

Percentage deviation

Average weight
(A) (B)

300mg or less ±10% ±20%

More than 300mg ±7.5% ±15%

49