Methods and Equipment which a mixture of solid and liquid, or of two

liquids, is rotated
Separation
at high speeds so that the mixture is separated into
What is separation?
its constituent
Separation may be defined as an operation that
parts by the action of centrifugal force.
brings about
Two basic types of centrifuge:
isolation and/or purification of a single chemical
constituent or sedimentation type of centrifuge depends on
differences in the densities of the two or more
a group of chemically related substances.
phases comprising the mixture. This instrument is
two general capable of separating both solid–liquid and liquid–
categories of separation liquid mixtures.

Simple processes bring about separation of Filtration centrifuges, however, are limited to the
constituents through a single mechanical separation of solid–liquid mixtures only.
manipulation. Some examples of this type are the
Filtration
use of:
Filtration is the process of separating liquids from
• A separatory funnel or pipette to separate two
solids with
immiscible liquids
the purpose of obtaining optically transparent
such as water and ether
liquids.
• A distillation process to separate two miscible
This is accomplished by the intervention of a porous
liquids such as benzene
substance, called
and chloroform
the filter or the filtering medium. The liquid that has
• A garbling process to separate solids passed

• Centrifugation, filtration, and expression through the filter is called the filtrate.
processes to separate
Filtering media
solids from liquids
Filter paper
Processes in this category are limited usually to
Membrane filter media are produced from pure
separations of
cellulose, cellulose derivatives, and polymeric
relatively simple mixtures or solutions. materials

Complex processes usually require formation of a Cotton Filters—A small pledget of absorbent cotton,
second loosely inserted in the neck of a funnel, adequately
serves to remove large particles of extraneous
phase by addition of either a solid, liquid, or gas material from a clear liquid.
plus mechanical
Glass-Wool Filters—When solutions of highly
manipulation to bring about effective separation. reactive chemicals, such as strong acids, are to be
Example: aspirin filtered, filter paper cannot be used. In its place
glass wool may be used just as one uses absorbent
centrifugation cotton for filtering. This material is resistant to
This apparatus consists essentially of a container in ordinary chemical action, and when properly
packed into the neck of a funnel it constitutes a
very effective filtering medium.
Sintered-Glass Filters—These filters have as the Growth of crystals or amorphous particles
filtering medium a flat or convex plate consisting of
Review
particles of Jena glass powdered and sifted to
produce granules of uniform size that are molded Dissolution rate
together. The plates can be fused into a glass
apparatus of any required shape. Surface area – particle size

Other filtering media Crystal form and amorphous form

Filter press Salt form and free form

Centrifugal filter State of hydration (anhydrous and hydrated form)

Vacuum filter Supersaturation ?

Sand-bed filter Evaporation of solvent from a solution (cooling

solution)
Charcoal filter
Shape of crystal depends:
Paperpulp filter
Impurities on solution
Porous porcelain filter
pH
Powders
Rate of stirring
Advantage and disadvantage of powders
Rate of cooling
a. Advantages of powders
Solvent
(1) Flexibility of compounding
NOTE:
(2) Good chemical stability
Very rapid rate of
(3) Rapid dispersion of ingredients because of the
small particle size Crystallization  impurities being included in
crystals by entrapment
b. Disadvantages of powders
Spray drying
(1) Time-consuming preparation
Atomization of a solution of 1 or more solids via
(2) Inaccuracy of dose nozzle, spinning disk or other device followed by
evaporation of the solvent fro the droplets
(3) Unsuitability for many unpleasant - tasting,
hygroscopic, and deliquescent drugs Particle size reduction
Production Methods Milling
Molecular aggregation Milling is the mechanical process of reducing the
particle size of solids (comminution) before mixing
Spray drying
wi th other components, further processing, or
Molecular aggregation incorporation into a final product. The particle size
of a powder is related to the proportion of the
Precipitation and crystallization
powder that can pass through the opening of
Achieve in 3 condition in succession: standard sieves of various dimensions in a specified
amount of time.
State of supersaturation
Advantages of mi l ling
Formation of nuclei
(a) Increases the surface area, which may increase Dust-free operation
the dissolution rate as well as bioavailability
Durability, simplified construction
(b) Increases extract ion, or leaching, from animal
Suitable feed and outlet capacities are additional
glands and from crude vegetable extracts
considerations in equipment selection.
(c) Facilitates drying of wet masses by increasing
the surface area and reducing the distance that
Three Broad Categories of Comminution based on
moisture must travel to reach the outer surface.
feed and product size:
(2) Disadvantages of milling
1. Coarse crushers
(a) Can change the polymorphic form of the act ive
Employed here the size of the feed materials
ingredient , rendering tess active
relatively large ranging from 1 ½ to 60 inches in
(b) Can degrade the drug as a result of heat buildup, diameter
oxidation, or
Frequently use in mineral crushing industry
adsorption of unwanted moisture because of assigment
increased surface area
ex. Jaw, gyratory, roll, and impact crushers
(c) Decreases the bulk density of the active
Coarse crushers
compound and excipients,
Jaw crusher
causing f low problems and segregation.
Double roll crushers
(d) Decreases the particle size of the raw materials
and may create medium crushing of various ore and rock with low
hardness in industrial sectors
problems with static charge, which may cause
particle aggregation and Impact crushers
decrease the dissolution rate Fine-pulverizer
(e) Increases surface area, which may promote air 2. Intermediate grinders
adsorption and inhibit wettability
Use for feed materials of relatively small size and
Comminution provide products that fal between 20-200 mesh
Cutting, chopping, crushing, grinding, milling, ex. Rotary cutters, disk, hammer, roller, and chaser
micronizing and trituration mills
Vegetable and other fibrous materials  cutting Small crusher/grinder
and chopping
3. Fine grinding mills
Methods and Equipments
Particles which pass thru 200 mesh sieve to micron
Equipment also has been designed to combine the range
sieving and milling steps into a single operation.
ex. Ball, rod, hammer, colloid, and fluid-energy mills
Important properties in selecting equipment
high-speed mechanical screen and centrifugal
Should be fabricated of materials that are classifier
chemically and mechanically compatible with the
substance being processed. Colloid mill

Easy to disassemble for cleaning Three basic actions of comminuting equipment

1. Attrition
This involves breaking down of the material by Principle: Provides particle-size reduction mainly
rubbing action between two surfaces. through compression (crushing) and shear.

Application: Grinding of fibrous materials where a The roller mill is quite versatile and can be used to
tearing action is required to reduce the fibers to crush a variety of materials.
powder

2. Hammer mills
2. Rolling
 Consist of a rotating shaft on which are
This uses a heavy rolling member to crush and mounted either rigid or swing hammers
pulverize the material. (beaters).

In actual practice, some slight attrition takes place  This unit is enclosed with a chamber
between the face of the roller and the bed of the containing a grid or removable screen
mill. through which the material must pass.

3. Impact  On the upper part is the feed hopper.

This involves the operation of hammers (or bars) at  As the material enters the chamber, the
high speeds. These strike the lumps of material and rapidly rotating hammers strike against it
throw them against each other or against the walls and break it into smaller fragments
of the containing chamber.
Swept downward against screen  additional
Result: Small particles of required size are hammering  small size pass thru screen
produced.
Oversize particles are hurled upward into chamber
In some instances high-velocity air or centrifugal  further blows by the revolving hammers
force may be used to generate high-impact
Hammer mill
velocities.
3. Centrifugal-Impact Mills and Sieves
Fine Grinding Mills
Useful to minimize the production of fine particles
1. Roller Mills
(combine sieving and milling)
2. Hammer mills
The mill consists of a nonrotating bar or stator that
3. Centrifugal-Impact Mills and Sieves is fixed within a rotating sieve basket.

4. Cutter Mills The particles that are smaller than the hole size of
the sieve can pass through the mill without
5. Attrition Mills
comminution; however, the particles or
6. Chaser Mills agglomerates larger than the hole size are directed
by centrifugal force to impact with the stator.
7. Pebble or Ball Mills
Sieve baskets also can be constructed to have a
8. Vibrating Ball Mills cutting edge that can aid in particle size reduction
9. Fluid-Energy Mills without impact with the stator

10. Centrifugal-Impact Pulverizes Centrifugal impact mill

1. Roller Mills 4. Cutter Mills

Consist of two rollers revolving in the same Useful in reducing the particle size of fibrous
direction at different rates of speed. materials and act by a combined cutting and
shearing action.
They consist of a horizontal rotor into which is set a Used for pulverizing and classifying extremely
series of knives and blades. This rotor turns within a small particles of many materials.
housing, and into it are set stationary bed knives or
The mills have no moving parts, grinding being
blades.
achieved by subjecting the solid material to
Cutter mill streams of high-velocity elastic fluids, usually air,
steam, or an inert gas.
5. Attrition Mills
The material to be pulverized is swept into violent
Make use of two stone or steel grinding plates, one
turbulence by the sonic and supersonic velocity of
or both of which revolve to provide grinding mainly
the streams.
through attrition.
Particles are accelerated to relatively high speeds
These mills are most suitable for friable or medium-
 collide  impact cause fracture of particles
hard, free-flowing material.
10. Centrifugal-Impact Pulverizes
Attrition mill
Effective for the reduction of the particle size of a
6. Chaser Mills
wide variety of materials ranging from very soft,
Chaser mills are so called because two heavy organic chemicals to hard, abrasive minerals.
granite stores, or chasers, mounted vertically like
Advantage: Suited well for the size reduction of
wheels and connected by a short horizontal shaft,
heat-sensitive substances.
are made to revolve or chase each other upon a
granite base surrounded by a curb. Large scale mixing equipments

Result: Fine powder Large-Scale Mixing Equipment

7. Pebble or Ball Mills The ideal mixer should produce a complete blend
rapidly with as gentle as possible a mixing action to
Sometimes called pot mill or jar mills
avoid product damage.
Principle: Attrition and impact.
It should be cleaned and discharged easily, be dust-
The grinding is effected by placing the substance in tight, and require low maintenance and low power
jars or cylindrical vessels that are lined with consumption.
porcelain or a similar hard substance and containing
1. Rotating-Shell Mixers
pebbles or balls of flint, porcelain, steel or stainless
steel. Advantage: Produces pulverization with a 2. Fixed-Shell Mixers
minimum loss of material
3. Sigma-Blade and Planetary Paddle Mixers
8. Vibrating Ball Mills
4. Vertical Impeller Mixers
Combination of attrition and impact, consist of a
5. Motionless Mixers
mill shell containing a charge of balls similar to
rotating ball mills. 1. Rotating-Shell Mixers
The shell is vibrated at some at some suitable The drum-type, cubical shaped, double-cone, and
frequency, rather than rotated. twin-shell blenders are all example of this class of
mixers.
Advantage of being free of rotating parts, and thus
can be integrated readily into a particle classifying 2. Fixed-Shell Mixers
system or other ancillary equipment.
The ribbon mixer, one of the oldest mechanical
9. Fluid-Energy Mills solid-solid blending devices, exemplifies this type of
mixer.
3. Sigma-Blade and Planetary Paddle Mixers The Wedgwood mortars do become smooth with
continued use
Sigma-blade and planetary paddle mixers are also
used for solid-solid blending, although most Porcelain mortars
generally as a step prior to the introduction of
Same sizes as Wedgewood mortars
liquids.
Have more attractive white, glazed surface but
4. Vertical Impeller Mixers
provide less shearing efficiency than Wedgewood,
Vertical impeller mixers, which have the advantage and less durable
or requiring little floor space, employ a screw-type
Ceramic mortars
impeller that constantly overturns the batch.
They have abradant interior working surfaces
5. Motionless Mixers
similar to Wedgewood but also less durable
These are in-line continuous processing devices
Clear glass mortars
with no moving parts.
These have smooth, nonporous interior surfaces,
They consist of a series of fixed flow-twisting or
making them useful for triturating drugs that stain.
flow-splitting elements.
Because of their smooth sides, not efficient for
Motionless/static mixer
reducing particle size of powders, especially crystals
Small scale mixing equipments
Application: making solutions and suspensions, and
Small-Scale Mixing Equipment for diluting creams and lotions

Mortar and pestle method combines comminution Filtration

and mixing in a single operation.
Filtration
It is particularly useful where some degree of
Filtration is the process of separating liquids with
particle size reduction as well as mixing is required,
the purpose of obtaining optically transparent
as in the case of mixtures of crystalline material.
liquids.
Mortars and Pestles
This is accomplished by the intervention of porous
WEDGWOOD MORTARS are heavy duty, durable substance, called the filter and the filtering
mortars available in various sizes: medium.

2, 4, 8, 16, 32 oz Filtering Media

They are made with abradant interior surfaces, The filtering medium, whether a filter paper,
making them ideal for particle size reduction synthetic fiber, or porous bed of glass, sand, or
stone, is composed of countless channels that
For making emulsions, where efficient shear is
impact porosity to the medium.
desirable

Because of their porous interiors, Wedgwood

mortars should not be used for:
The mechanism of filtration basically involves a two-
 Drugs that stain
step process:
 Drugs present in small quantities
A) The filter medium itself resists the flow of solid
 Very potent or hazardous drugs material while permitting the passage of liquid.

Particular care must be taken with cleaning B) During the course of the filtration, the
suspended, solid material builds up on the filter
medium and thereby forms a filter bed, which acts d) Infusorial earth
as a second, and often more efficient filter medium.
Filter aid which forms a fine surface deposit to
Types of filter media screen out all solids, preventing the clogging of the
supporting filtering media
1. Filter Paper
Composed of clays, clays have a property of forming
Most frequently employed in clarification processes
a fine cake surface on the filter paper which screen
required
out all particle contaminants
Only High-quality filter paper should be used to
e) Filter cloth
ensure maximum filtering efficiency.
Woven from synthetic fiber like nylon, from natural
Whatman filter paper
fiber like cotton cloth and metal such as stainless
2. Membrane Filters wire cloth

Membrane filter media are produced from pure Used to strain simple syrup or syrup preparation
cellulose, cellulose derivatives, and polymeric
Nylon is often superior for pharm’l use since it is not
materials
affected by fungi and bacteria can be serilized by
All have an extremely uniform micropore structure autoclaving and negligible absorption properties
as well as an exceptionally smooth surface
f) Filter media, non woven
Basic tools for microfiltration in the preparation of
Bonded fabrics, felt and kraft paper
sterile solutions
Bonded fabrics – made by binding textile fabrics
Made of various esters of cellulose or from nylons,
with resins, solvents and plasticizers
teflons, polyvinyl chloride
Felt – fibrous mass free from bonding agents and
Thin membrane about 150 micrometer thick with
mechanically interlocked to yield specific pore
millions of pores/sq.cm of filter surface
diameter that have controlled particle retention
Pore range form 0.05 – 14 micrometer
Recommended for gelatinous solutions or with
Validated polyethersulfone membrane filter particulate matter (asbestos pad)
cartridges and capsules
Kraft paper – used as pharmaceutical standard
3. Other Filtering Media
It offers controlled porosity limited absorption
a) Cotton Filters. capacity and a relatively low cost

 A small pledget of absorbent cotton, loosely Note : plate and frame filter press is the simplest of
inserted in the neck of a funnel, adequately all pressure filters and the most widely used in
serves to remove large particles of commercial sale
extraneous material from a clear liquid.
g) Filter aids
b) Glass-Wool Filters
Special types of filter media
Application: Solutions of highly reactive chemicals
Act by forming highly porous and non compressible
such as strong acids
cake which retains solids
c) Sintered-Glass Filters.
Forms a fine surface deposit which screens out all
These filters have as the filtering medium a flat or solids, preventing them from contacting and
convex plate consisting of particles of Jena glass plugging the supporting filtering medium
powdered and sifted to produce granules of
Examples
uniform size that are molded together.
Diatomite (diatomaceous earth, kieselgur, celite,
super gel) – important since these are inert and
insoluble

Filter aids contribute to clarity improvement and

increase of filtration flow rate (amount added is
NMT 0.05%)

Funnels

Funnels are conical-shaped utensils intended to

facilitate the pouring of liquids into narrow-
mouthed vessels

They also are used widely in pharmacy for

supporting filter media

Funnels may be made of glass, polyethylene, metal,

or any other material that serves a specific purpose.

Rapid Filtering Apparatus

1. Vacuum Filtration

One of the first practical efforts made to create a

vacuum to aid filtration was by means of the
Bunsen-pump.

Its action depends on the principle that a column of

water descending through a tube from a height is
capable of carrying with it the air contained in a
lateral tube, if the latter is placed properly.

2. Filtration Under Pressure

The material to be filtered enters the apparatus

under pressure through a pipe at the bottom and is
forced into one of the many chambers

The End

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