Particulate Technology

(MSc Ind. Microbiology)

By
Dr Vikram Kumar Yadav
Asst Professor, AIB
Amity University Rajasthan
Particulate Technology: Particle Size, Size reduction, Size separation
Size reduction: It is the process of reducing substances to
smaller particles.
Size separation: It is a process in which particles of desired
size are separated from other fractions.

Objectives of size reduction

•Size reduction leads to increase of surface area.
Example-I: The rate of dissolution of solid drug particles
increases many folds after size reduction. Griseofulvin, an
antifungal drug, when administered in its micronized form
shows around five times better absorption.
Example-II: The absorptive power of charcoal and kaolin
increases after size reduction due to increase in surface area.
Cont…….
Objectives of size separation
•Size reduction produces particles in narrow size range. Mixing of powders
with narrow size range is easier.
•Pharmaceutical suspensions require finer particle size. It reduces rate of
sedimentation.
•Pharmaceutical capsules, insufflations (i.e. powders inhaled directly into
the lungs), suppositories and ointments require particles size to be below
60m size.
•Any solid materials, after size reduction, never gives particles of the same
size but contains particles of varying sizes. The size-reduced particles are
then passed through sieves to get fractions of narrow size range.
•During tablet granulation the granules should be within narrow size range,
otherwise, weight variation will take place during tablet punching.
Mechanical Methods of size reduction
Method Diagram Common
Examples

Cutting Scissors/
Cutter mill
Approximate
Compression Roller mill/
increase in
Crusher mill
fineness of
product
Impact Hammer
mill
Attrition
Fluid energy
(Pressure and
mill
friction)
Manual method of size reduction:
• Trituration is the continuous rubbing or grinding of the powder in a
mortar with a pestle. This method is used when working with hard,
fracturable powders.
• Pulverization by Intervention is used with hard crystalline powders that
do not crush or triturate easily, or gummy-type substances. The first step is
to use an "intervening" solvent (such as alcohol or acetone) that will
dissolve the compound. The dissolved powder is then mixed in a mortar or
spread on an ointment slab to enhance the evaporation of the solvent. As
the solvent evaporates, the powder will recrystallize out of solution as fine
particles.
• Levigation reduces the particle size by triturating it in a mortar or
spatulating it on an ointment slab or pad with a small amount of a liquid in
which the solid is not soluble. The solvent should be somewhat viscous
such as mineral oil or glycerin. This method is also used to reduce the
particle size of insoluble materials when compounding ointments and
suspensions.
Uses of size reduction methods

Degree of size Typical methods Examples

reduction

Large pieces Cutter or compression Rhubarb

mills

Coarse powders Impact mills Liquorice,

cascara
Fine powders Combined impact and Rhubarb ,
attrition mills belladonna

Very fine Fluid energy mills Vitamins and

powders antibiotics
Size Separation
SIEVE ANALYSIS
• STANDARDS OF SIEVES
It is required that wire-mesh sieves will be made from wire of uniform,
circular cross-section and for each sieve the following particulars are
stated:
20, 40, 60, 80, 100, 120
Number of sieve
This is the number of meshes in a length of 25.4mm or 2.54 cm (i.e. 1
inch), in each direction. 25 .4 m m
(1 inch)

w ire
diam eter

2 5.4 m m
(1 inch)

5 m esh
sieve
SIEVING METHOD

In this method, the fine powder is separated from the

coarse powder by using sieves of desired number.
The degree of fineness of a powder is known with
the help of sieve through which the powdered
material is passed. Sieves are numbered in order to
distinguish from each other. Size separation of
powder is done by passing the powdered material
through a set of sieves. Sieves are arranged in
descending order i.e. sieve of larger size is at the top
and the smallest one at the bottom. The bottom
sieve is attached to the receiving pan.
• The working of mechanical sieving devices are based on any
of the following methods.
1. Agitation 2. Brushing 3. Centrifugal
• Agitation methods Sieves may be agitated in a number of different ways,
such as:
1. Oscillation : This sieve is mounted in a frame that oscillates back and
forth. It is a simple method but the material may roll on the surface of
the sieve.
2. Vibration : The sieve is vibrated at high speed by means of an electric
device. The rapid vibration is imparted to the particles on the sieve which
helps to pass the powdered material through it.
3. Gyration : In this method, a system is made so that sieve is on rubber
mounting and connected to an eccentric fly wheel. This gives a rotary
movement of small amplitude to sieve which hi turn gives spinning
motion to the particles that helps to pass them through a sieve. Agitation
methods are not continuous methods’ but can be made so by inclination
of the sieve and the provision of separate outlets for undersize and
oversize particles.
• Brushing methods In this case, a brush is used to move the
particles on the surface of the sieve and to keep the meshes
clear. The brush is rotated in the middle in the case of a
circular sieve but spiral brush is rotated on the longitudinal
axis in case Of a horizontal cylindrical sieve.
• Centrifugal methods In this method, a high speed rotor is
fixed inside the vertical cylindrical sieve, so that on rotation of
rotor the particles are thrown outwards by centrifugal force.
The current of air which is produced due to high speed of
rotor helps in sieving the powder.
Grading Powder
OFFICIAL STANDARDS FOR POWDERS The Indian Pharmacopoeia
has laid down the standards for powders for pharmaceutical
purposes. The I.P. specifies five grades of powder which are as
under:
1. Coarse powder : A powder of which al! the particles pass
through a sieve with nominal mesh aperture of 1.70 mm (No.
10 sieve) and not more than 40.0 per cent through a sieve
with nominal mesh aperture of 355 urn (No. 44 sieve) is
called coarse powder.
2. Moderately coarse powder: A powder of which all the
particles pass through a sieve with nominal mesh aperture of
710 nm (No. 22 sieve) and not more than 40.0 per cent
through a sieve with nominal mesh aperture of 250 nm (No.
60 sieve) is called moderately coarse powder.
Grading Powder……Conti….
3. Moderately fine powder : If all the particles of a powder pass
through a sieve with nominal mesh aperture of 355 µm (No.
44 sieve) and not more than 40.0 per cent through a sieve
with nominal mesh aperture of 180 µm(No. 85 sieve), it falls
in this group.
4. Fine powder : In case all the particles pass through a sieve
with a nominal mesh aperture of 180 µm (No. 85 sieve), it is
called fine powder,
5. Very fine powder : If all the particles of the powder pass
through a sieve with a nominal mesh aperture of 125 µm (No.
120sieve), it is said to be very fine powder.
 MIXING

Mixing may be defined as an operation in which two or more

components, in a separate or roughly mixed condition, are
treated so that each particle lies as nearly as possible in
contact with a particle of each of the other ingredients.
• APPLICATIONS:
– Uniformity , composition and dose accuracy.
– Enhances the rate of chemical reaction, rate of dissolution
According to physical stability of mixture:-
• Positive mixtures (Reversible mixing)
Positive mixtures are formed from materials such as gases and
miscible liquids, where irreversible mixing would take place,
by diffusion, without the expenditure of energy provided time
is unlimited. In general, such materials do not present any
problems in mixing.
 MIXING….conti…
• Negative mixtures (Irreversible mixing)
Suspensions of solids in liquids are examples of negative
mixtures that require work for their formation, and the
components of which will separate unless work is continually
expended on them.
• Neutral mixtures
Neutral mixtures are static in their behavior, the components
having no tendency to mix spontaneously, nor do they
segregate when mixed.
e.g. Pastes, ointments and mixed powders.
 MIXING….conti…
• According to state of matter:-
• a) Solid-solid mixing- Powder
• b) Solid-liquid mixing
Mixing of soluble solid in liquid –Solution
Mixing of insoluble solid in liquid- Suspension
• c) liquid-liquid mixing
Mixing of liquid in immiscible liquid – Emulsion
Mixing of liquid in miscible liquid- Solution
 FILTRATION
• Filtration may be defined as the separation of a solid from a
fluid by means of a porous medium that retains the solid but
allows the fluid to pass.
• Clarification - When solid are present in very low
concentration in fluid, ex. Not exceeding 0.1 w/v, the process
of its separation from liquid is called as clarification.
• Straining - When we need to remove large visible particles by
using coarse filtration medium(cotton wool or muslin), the
process is called as straining.
• Mechanism of filtration
Slurry: The suspension of solid and liquid to be filtered.
Filter medium: The porous medium used to retain the solids.
Filter cake: The accumulation of solids on the filter medium.
Filtrate: The clear liquid passing through the filter and
collected in the receptor.
 FILTRATION

..... ..
. ................... Filter cake
...................
Slurry
Filter medium

Filtrate
 FILTRATION
• Process of Filtration
– Porous of the filter medium should be smaller than the size of
particles to be separate.
– Filter medium(Filter paper) is placed on the support(mesh)
– Slurry is placed over the filter medium
– Due to pressure difference across the filter fluid flows through the
filter medium
– Gravity will acting over the medium & solid are retained on the
surface of the medium
• Application of Filtration
– Production of Sterile products 
– HEPA Filter (High Efficiency Particulate Air filter) / Laminar Air Bench
– Membrane Filters
– Production of Bulk Drugs
– Production of Liquid Dosage
– Waste water treatments
 FILTRATION
• Theory of Filtration
Darcy’s Law
V = KAΔP / ηl
Where
V= Volume of filtration
K= Permeability coefficient and is dependent on the nature of the
precipitate to be filtered and the filter medium
A= Area of filter bed
ΔP= Pressure difference on the liquid and below the filter medium
η= Viscosity of the fluid
l= Thickness of filter cake
 FILTRATION
• Factors Affecting Rate of Filtration
– Pressure 
– Viscosity
– Surface Area of Filter Media
– Temperature of Liquid to be filtered
– Particle Size (Clogging with fines)
– Pore size of filter media
– Thickness of Cake
– Nature of Solid material (Porosity of Filter Cake)
• Properties of Ideal Filter Media
– High retention power
– Absorb negligible amount of Materials
– Resistant to corrosive action of liquid
– Chemically inert
– Sufficient Mechanical Strength
 FILTRATION
• Types of Filter / Filter Media Types
– Filter Paper
–  Cotton Wool
– Glass Wool
– Asbestos
– Fine Muslin
– Filter Cloth
– Membrane Filter
– Sintered Glass
 Evaporation
Evaporation is the process of removal of solvent from
the solution by boiling the liquid in a suitable vessel
and withdrawing the vapour, leaving a concentrated
product.

Applications of Evaporation
• Evaporation process is used in the manufacture of
bulk drugs, particularly in pharmaceutical industries.
• Evaporation is used in the manufacture of biological
products. e.g. Insulin, enzymes and hormones.
• In demineralization of water.
 Evaporation
Factors Effecting on Evaporation
1. Temperature
2. Temperature and time of evaporation
3. Temperature and moisture content
4. Types of product required
5. Effect of concentration
6. Surface area
7. Vapour pressure of the liquid to be evaporated
Classification of evaporation equipment
I. Natural circulation evaporators- 1. Evaporating pans 2.
Evaporating still 3. Short tube evaporators
II. Forced circulation evaporators
III. Film evaporators- 1. Climbing film evaporators 2. Horizontal
film evaporators
 Distillation
Distillation is defined as the separation of the components of a
liquid mixture by a process involving vaporization and
subsequent condensation at another place.
Applications
– Separation of volatile oils,
– Separation of drugs obtained from plant and animal
sources- Vit . A from fish liver oil,
– Purification of organic solvents -absolute alcohol (100%),
– Purification of drugs obtained from chemical process,
– Manufacture of official preparations -sprit of nitrous ether,
sprit of ammonia, D.water and water for inj
 Distillation
Distillation Evaporation Drying
Distillation Evaporation Drying Slow
Vaporization of bulk Vaporization of bulk evaporation of wet
liquid above boiling liquid below boiling solid bulk (small
point   point amount of liquid)
Product desired is Product desires is Product desires is
distillate(solvent concentrated Solid residue(dried
used) liquid(concentrated solute)
solute)
Process of Process of removal Process of complete
separation of the of the liquid solvent  removal of the liquid
components of solvent
liquid mixture
 Centrifugation
Centrifugation is a process used to separate or concentrate
materials suspended in a liquid medium. The theoretical basis
of this technique is the effect of gravity on particles (including
macromolecules) in suspension. Two particles of different
masses will settle in a tube at different rates in response to
gravity.
A particle, whether it is precipitate, a macromolecule or cell
organelle when rotated at high speed is subjected to a
centrifugal force. Centrifugal force is defined as
F=mw2r
Where F=intensity of centrifugal force
m= effective mass of sedimenting particle
w= angular velocity of rotation
r = distance of migrating particles from central axis of rotation
 Extraction
Extraction defined as the treatment of the plant or animal
tissues with solvent, whereby the medicinally active
constituents or API are dissolved & most of the inert matter
remain undissolved

In this method the wanted components are dissolved by the use

of selective solvents known as menstrum & undissolved part
is a marc.

Type of extracts
– Dry extract (Tab, cap.) E.g. belladonna extract
– Soft (Ointment, suppository) E.g. glycerrhiza extract.
– Liquid : As tincture.
 Extraction
Ideal properties of the solvents :
1. Be highly selective for the compound to be extracted.
2. Not react with the extracted compound or with other
compounds in the plant material
3. Have a low price.
4. Be harmless to man and to the environment.
5. Be completely volatile.
6. Should not mix up with water.
7. Should have the big capacity in relation to extractive.
8. The density of solvent should be difference from water
density.
9. Should have the minimum viscosity.
 Extraction
 Methods of extraction
– Infusion
– Decoction
– Digestion
– Maceration
– Percolation
– Continues hot extraction (Soxhlet Extraction)
– Ultrasonication-Assisted Extraction
 Extraction
Infusion :
Fresh infusions are prepared by macerating the soft in nature
crude drug for a short period of time with cold or boiling
water. These are dilute solutions of the readily soluble
constituents of crude drugs.
Types of Infusion :
Fresh Infusion : e.g. Infusion of orange
Concentrated Infusion : e.g. Concentrated infusion of Quassia
Decoction :
In this process, the crude drug is boiled in a specified volume
of water for a defined time; it is then cooled and strained or
filtered. This procedure is suitable for extracting water-
soluble, heat stable constituents. e.g. Tea , Coffee
 Extraction
Digestion :
This is a form of maceration in which gentle heat is used
during the process of extraction. It is used when moderately
elevated temperature is not objectionable. The solvent
efficiency of the menstruum is thereby increased. e.g.
Extraction of Morphine
Maceration : In this process solid ingredients are placed in a
stoppered container with the whole of the solvent and
allowed to stand for a period of at least 3 days (3 - 7 days)
with frequent agitation, until soluble matter is dissolved. The
mixture is then strained (through sieves / nets), the marc
pressed and the combined liquids clarified (cleaned by
filtration) after standing.
 Extraction
Percolation :
It is continuous downward displacement of the solvent
through the bed of crude drug material to get extract. Most
frequently used to extract active ingredients in the
preparation of tinctures and fluid extracts. It is the method of
short successive maceration or process of displacement .
A percolator (a narrow, cone-shaped vessel open at both
ends) is generally used. conical cylindrical
Steps in percolation :
Size reduction
Imbibition
Packing
Maceration
Percolation
Percolator
Continuous Hot Percolator (soxhlet extraction)
 Merit and Demerit of Soxhlet
Merits :
Large amount of drug can be extracted with much smaller
quantity of solvent.
Tremendous economy in terms of time, energy & ultimately
financial inputs.
Small scale used a batch-process.
Becomes more economical when converted into continuous
extraction.
Procedure on large scale.
Demerits :
Physical nature of drug.
Solvent.
Chemical constituent of drug.
Ultrasonication-Assisted Extraction:
The procedure involves the use of ultrasound waves, which have
frequencies higher than 20 kHz, have great effects on
extraction yield and kinetics.
Under ultrasonic action solid and liquid particles are vibrated
and accelerated and, because of that solute quickly diffuses
out from solid phase to solvent.
Ultrasound assisted extractors are ultrasonic baths or closed
extractors fitted with an ultrasonic horn transducer. The
mechanical effects of ultrasound induce a greater penetration
of solvent into cellular materials and improve mass transfer.