PHARM 617T Pharmaceutics-IVB(industrial Pharmacy)

Assignment

Submitted to
Teacher Name : Dr. Syed Haroon Khalid
Submitted by
Student Name : Hafiz Muhammad Ehtisham Khaliq
Roll No : 6648
Semester : 8th
Session : 2016-2021

Department of Pharmacy Practice

Faculty of Pharmaceutical Sciences
Government College University Faisalabad
 Contents:
1. Filter aids
2. Filter equipments
3. Compression, compaction and consolidation of powdered solids
4. Mass-volume relationships and different techniques for measuring
volume of powder samples
5. Effect of applied force
Q.1 What are filter aids? What are its various properties? Which are the
examples of filter aid materials? Write a brief note in filter aid materials.
Filter aids:
‘‘The substances which when added to the liquid to be filtered, reduce the
resistance of the filter cake and increase the filtration.’’
Why are the filter aid materials added to the filter feed?
Usually, the resistance to flow due to the filter medium itself is very low, but
increases as a layer of solids builds up, blocking the pores of the medium and
forming a solid, impervious cake. Poorly flocculated solids offer higher resistance
than do flocculated solids or solids providing high porosity to the cake. In the case
of cake filtration, the rate varies with the square of the volume of liquid. When the
volume of the filter cake solids per unit volume of filtrate is low, the solids formed
on the filter medium may penetrate the void space, thus making the filter medium
more resistant to flow. At a higher concentration of solids in a suspension, the
bridging over of openings over the void space, rather than blinding of the openings,
seems to predominate. Slimy or gelatinous materials, or highly compressible
substances, form impermeable cakes with high resistance to liquid flow. The filter
medium becomes plugged or slimy with accumulation of solids, and the flow of
filtrate stops. A filter aid acts by reducing this resistance.
How are the filter aids act:
Filter aids are a special type of filter medium. Ideally, the filter aid forms a fine
surface deposit that screens out all solids, preventing them from contacting and
plugging the supporting filter medium. Usually, the filter aid acts by forming a
highly porous and non-compressible cake that retains solids, as does any depth
filter. The duration of a filtration cycle and the clarity attained can be controlled as
density, type, particle size, and quantity of the filter aid are varied. The quantity of
the filter aid greatly influences the filtration rate. If too little filter aid is used, the
resistance offered by the filter cake is greater than if no filter aid is used, because
of added thickness to the cake. On the other hand, if high amounts of filter aid are
added, the filter aid merely adds to the thickness of the cake without providing
additional cake porosity.
Filter aid quantity Vs flow rate:
Figure is a typical plot of filter aid concentration
versus permeability. In the figure, flow rate and
permeability are directly proportional to each
other. At low concentrations of filter aid, the flow
rate is slow because of low permeability. As the
filter aid concentration increases, the flow rate
increases and peaks off. Beyond this point, the
flow rate decreases as the filter aid concentration is
increased.
How are the filter aid materials applied?
Filter aids may be applied by precoating or body-mix techniques.
Precoating:
Precoating requires suspending the filter aid in a liquid and recirculating the slurry
until the filter aid is uniformly deposited on the filter septum. The quantity varies
from 5 to 15 pounds per 100 square feet of filter area, or that sufficient to deposit a
cake Vie to Vs inches thick. The liquid is preferably a portion of the feed or
retained filtrate from a prior cycle, since the physical properties of the precoat
liquid must approximate those of the material to be filtered. Precoating should
proceed at the same flow rates and pressures to be used in final filtration, and the
transition from precoat liquid to regular feed must be rapid to prevent disruption of
the cake.
Body-mix technique:
Body mix (direct addition of filter aid to the filter feed) is more common in batch
pharmaceutical operations. The filter aid, 1 to 2 pounds per pound of contaminant,
or 0.1 to 0.5% of total batch weight, is mixed into the feed tank. This slurry is
recirculated through the filter until a clear filtrate is obtained; filtration then
proceeds to completion. The body-mix method minimizes equipment requirements
and cross-contamination potentials.
Selection of filter aid materials:
Filter aids are chosen by trial and error in either laboratory or plant. the filter aid is
usually selected to give acceptable filtrate at the highest flow rate; however, in
pharmaceutical operations in which quality is a primary consideration, the
selection usually favours the fine grades, which yield low flow rates. The most
important pharmaceutical factor is inertness. A filter aid may have such extensive
absorption properties that desired coloured substances and active principles are
frequently removed. The total quantity of any ingredient absorbed may be small,
but it may be a considerable portion of the original concentration.
Properties of filter aid materials:
These are the following properties:
1. It should have a structure that permits formation of pervious cake.
2. It should have a particle size distribution suitable for the retention of solids, as
required.
3. It should be able to remain suspended in the liquid.
4. It should be free of impurities.
5. It should be inert to the liquid being filtered.
6. It should be free from moisture in cases where the addition of moisture to the
fluid would be undesirable.
7. It should have low specific gravity.
8. It should be free from moisture.
9. It should be chemically inert.
10. It should be insoluble in liquids.

Examples of filter aid materials:

i. Diatomaceous earth
ii. Expanded perlite
iii. Asbestos
iv. Cellulose
v. Carbon
Diatomite (diatomaceous earth):
It is the most important filter aid. Processed from fossilized diatoms, it has
irregularly shaped porous particles that form a rigid in-compressible cake.
Chemical composition:
Diatomite is primarily silica, since it is relatively inert And insoluble.
Advantages:
1.Wide size range available.
2. Fines reduced by calcination.
3. Can be used for very fine filtration.
Disadvantages:
It is Slightly soluble in dilute acids and alkalies.
Expanded perlite:
Perlite forms filter cakes that are 20 to 30% less dense than diatomaceous cakes.
Chemical composition: Silica and aluminosilicates
Advantages:
1.wide size range available.
2. It is not capable of finest reduction.
3. It is economical than diatomite.
Disadvantages:
1.It is more soluble than diatomite in acids and of diatomites.
2. Alkalies; may give highly compressible cakes.
Asbestos:
It is also commercially available. It has limited applications because of leaching of
fibres into the filtrate that might be toxic. Asbestos filters may be used in
pharmaceutical industry if their application is followed by membrane filtration.
Chemical composition: Aluminosilicate
Advantages:
1.It is usually used in conjunction with diatomites. 2. It has very good retention on
coarse screens.
Disadvantages:
1.its chemical properties are similar to perlite. 2. It is expensive.
Cellulose:
Cellulose is highly compressible and costs two to four times more than diatomite
and perlite. It is reserved for applications where the liquids may be incompatible
with silica compounds.
Chemical composition: Cellulose
Advantages:
1.It is used mainly as a coarse precoat. 2. It has excellent chemical resistance. 3. It
is slightly soluble in dilute and strong alkalies, none in dilute acids.
Disadvantages:
It is expensive.
Carbon:
Chemical composition: Carbon
Advantages:
It may be used for filtering strong alkaline solutions.
Disadvantages:
1.It is available in coarser grades only.
2. It is expensive.

Filter aids
Q.2 What are filtration equipments? Classify the filters based on the driving
force? Which filters are mostly used in Pharmaceutical industries?
Filtration equipments:
Filtration equipments are the equipments that are used to filter, thicken, or clarify a
mixture of different elements.
Classification of filters based on driving force:

Gravity filters:
Gravity filters rely on gravity generated low operating pressure (usually less than
1.03 × 104 N/m2) and give low filtration rates unless very large surfaces areas are
used, which limits their use on a large scale. Gravity filters employing thick,
granular beds are common in water treatment, where clarification of water is done
prior to deionization or distillation.
Properties:
1. Simple
2. Cheap
Use:
These are frequently used in laboratory filtration where volumes are small and low
filtration rate is relatively insignificant.
Filtering medium:
The filtering medium may consist of sand or cake beds, or for special purposes, a
composition containing asbestos, cellulose fibers, activated charcoal, diatomaceous
earth, or other filter aids.

Examples of gravity filters:

1) Sand gravity filters
2) Candles gravity filters
3) Tray and frame gravity filters
4) Gravity bag
Sand gravity filters:
Sand filters are the most preferred for water treatment.
Types:
a) Slow sand filters
b) Rapid sand filters
a)Slow sand filters:
Operating velocity:
Slow sand filters operate with a velocity of 0.1—0.2 m/h down through the bed.
Function:
They function largely by straining through a biological layer that forms on the
surface of bed.
Cleaning:
They are cleaned occasionally by the reasonably complete removal of this layer,
without disturbing the rest of bed.
Advantages:
i. Simple to construct and operate
ii. Cheaper
iii. Physical, chemical and bacteriological quality of water is high
iv. Reduces bacterial count by 99.9% and E.coli count by 99%
Disadvantages:
i. Raw water turbidity must generally be low.
ii. Raw water must not have high algae counts.
iii. Colour removal is fair to poor.
iv. Unpredictable filter run times necessitate lengthy pilot studies.
b)Rapid sand filters:
Operating velocity:
Rapid sand filters utilize a velocity of 5—15 m/h.
Function:
They function by depth filtration within the bed.
Cleaning:
They are cleaned frequently by cessation of process flow, followed by a reverse
upward flow of wash water at such a rate that the bed expands and releases the
trapped dirt particles. This cleaning flow may be augmented by some form of
agitation, such as injecting compressed air below the bed or hydraulic jets
impinging on the surface.
Advantages:
i. Very effective in removing turbidity/large particles
ii. Higher filter rate (4000—12000 litres per hour per m2)
iii. No limitation regarding initial turbidity level
iv. Cleaning time takes only several minutes
v. The filter bed occupy less space
vi. There is more flexibility in operation
vii. Rapid sand filters can deal with raw water directly. Non preliminary storage
is needed
Disadvantages:
i. Not effective in removing bacteria, viruses, protozoa, fluoride, arsenic salts,
and organic matter
ii. High investments and operational costs
iii. Frequent cleaning required (every 24—72 hour)
iv. Skilled supervision essential
v. Highly energy demanding
vi. Treatment of backwashing water and sludge necessary
Candles:
Small scale purification of water may use
porous ceramics as a filter medium in the form
of hollow ‘‘candles’’. The fluid passes from
the outside through the porous ceramics into
the interior of the hollow candles.
Advantages:
i. Highly effective against most water-
bone pathogens
ii. Operate consistently regardless of
turbidity
iii. No addition of chemicals to the water
iv. Easy to use and maintain
v. Visual observation of water quality
improvements (turbidity reduction)
vi. Excellent cake discharge
vii. Minimum floor space
viii. Adapts readily to slurry thickening
Disadvantages:
i. Low viral removal
ii. No residual protection
iii. High cost
iv. Systems require regular cleaning to restore normal flow rate (each week or
two weeks)
v. Candles must be changed (life expectancy of 6 months or to 2 years)
Tray and frame filters:
Adaptation:
These are best adapted for exceptionally slow, difficult filtrations and for
exceptionally soft or fine-grained precipitates, which clog the filters under the
slightest pressure or pass through the openings of cloth.

Advantages:
i. simple structure
ii. large filtration area
iii. flexible operation
iv. easy to manufacture with corrosion-resistant material
v. low water content of filter cake
vi. can be fully washed
Disadvantages:
i. Feed inlet easy be blocked
ii. cake difficult to remove
iii. cannot run continuously
iv. a small amount of processing
v. ordinary plate easy to damage
vi. large cloth consumption
vii. clean manually
Gravity bags:
Gravity filters are applied to the concentration of magmas, such as milk of
magnesia. More efficient methods, however, particularly with respect to space
requirements, are available.

Vacuum filters:
These are employed on a large scale, but are rarely used for the collection of
crystalline precipitates or sterile filtration. Continuous vacuum filters can handle
high dirt loads, and an a volume basis, are cheap in terms of cost per gallon of the
filtered fluid. Vacuum filters are reliable machines, and therefore have gained
wide acceptance in the chemical, food and pharmaceutical industries. Except
nutzch filter, all have continuous operation.
Examples:
1. Rotary drum
2. Rotary disc
3. Horizontal belt
4. Nutzch

Rotary drum filters:

Construction:
The rotary drum vacuum filter is divide into sections, each connected to a
discharge head. Each filter unit is rectangular in shape with a curved profile so that
a number can be joined up to form a drug. Each unit has a perforated metal surface
and is covered with filter cloth.
Working:
The slurry is fed to a tank in which solids are held in suspension by an agitator. As
the drum rotates, each section passes through the slurry and vacuum draws filtrate
through the filter medium at the drum surface (pick-up zone). The suspended
solids deposit on the filter drum as a cake, and as rotation continues, vacuum holds
the cake at the drum surface. This is followed by washing and further drainage in
the drying zone. As the cake moves towards the discharge point, it may be
scrapped from the drum or it may be supported by strings until it breaks free under
gravitational forces (cake removal zone).
Cake discharge:
The cake discharge may be done through a scrapper, belt, roll or a string. Scraper
discharge mechanisms will suit cakes that could be scrapped readily and roller
discharge mechanism are better for thixotropic cakes.
String discharge filter:
A string discharge filter is useful in the manufacture of antibiotics, when the
removal of cake of mould mycelia is necessary.
Advantages:
i. Continuous operation.
ii. Uniform output.
iii. Minimum labour.
iv. Minimum change of filter cloth.
v. Human Error eliminated.
vi. Contamination eliminated.
vii. Negligible Maintenance.
viii. Minimum Floor Space requirement.
Disadvantages:
i. Complex equipment.
ii. In addition to the filter itself, some accessories are connected, e.g, vacuum
pump, vacuum receiver, slurry pump and agitators are required.
iii. The cake tends to crack due to air drawn through by the vacuum system, so
that washing and drying are not efficient.
iv. It is suitable only for straight-forward slurries.
Rotary disc filter:
Construction:
It consists of several discs, up to 15 in the larger machines, each made up from
sectors which are clamped together to form the disc. Each sector is connected to a
vacuum system, compressed air, and appropriate receivers, in the correct sequence,
by means of special rotating valves.
The operation sequence is similar to that of a drum filter.
Advantages:
i. Less floor space
ii. Lowest cost of filtration when compared to other vacuum filters
Horizontal belt filters:
Another adaptation of rotary vacuum filters is top feed horizontal belt filters.
Working:
Horizontal belt filters incorporate an endless and thick rubber belt of a complex
design to support the cake retained by the filter cloth. Once the belt reaches the end
of the vacuum box the cake drying portion of the cycle terminates and the cloth
leaves the rubber belt. The cloth continues moving, changes direction over the
discharge roll and the cake drops through a chute further handling.

Advantages:
i. High throughput and dewatering performance due to vacuum support and
inclined belt position.
ii. No consumables through endless filter belts.
iii. Optimum utilization of the belt: floated material is removed together with
the sediment on the discharge side
Nutzch filter:
The nutzch filter is the industrial version of the well
known laboratory scale, Buchner funnel except that it
is designed to operate under either vacuum or pressure.
Speciality:
These filters are well suited for handling flammable,
toxic, corrosive and odour noxious materials since they
are autoclaved and designed for use in hazardous and
ex-proof environments when extremely safe operation
is required.
Construction:
The filter consists of a densely perforated plate sufficiently strong to hold the cake
weight and the pressure that is exerted on the cake’s surface.
Working:
The paddles are available with the paddles consisting of two arms with slanted
blades that rotate in one direction to re-slurry the cake during washing and
discharge it at the end of the cycle. The filter is discharged with slurry and pressure
is applied to displace the filtrate leaving the cake retained over the filter medium.
Pressure filters:
Most of the pressure filters are batch operated but continuous filters are also
available. However, owing to the difficulty in removing the cake they are
mechanically complex and expensive so mainly used where the added value to the
product is high. The filtration rate is influenced , in broad terms, by the properties
of slurry. The trend is that the rate goes up with increased pressure, coarse
particles, particle distribution with high uniformity, non-slimy or non-gelatinous
solids, non-compressible cakes, lower liquid viscosity and higher temperatures.
Examples:
1) Filter leaf
2) Plate and frame filter press
3) Disc
4) Cartridge
5) Membrane
Filter leaf:
Construction:
The filter leaf is probably the simplest form of filter, consisting of a frame
enclosing a drainage screen or grooved plate, the whole unit being covered with
filter cloth. The outlet of the filtrate connects to the inside of the frame which
represents a vertical section through the leaf. The frame may be of circular, square
or rectangular shape. In use, the filter leaf is immersed in the slurry and the
vacuum system is connected to the filtrate outlet.
Advantage:
The method has the advantage that the slurry can be filtered from any vessel and
cake can be washed simply by immersing the filter in a vessel of water.
Alternative method:
An alternative method is to enclose the filter leaf in a vertical vessel.
Example:
A typical example of this kind is sweetland filter or candle filter.
Plate and frame filter:
Principle :
The mechanism is surface filtration. The slurry enters the frame by pressure and
flows through the filter medium: The filtrate is collected on the plates and sent to
the outlet. A number of frames and plates are used so that surface area increases
and consequently large volumes of slurry can be processed simultaneously with or
without washing.
Construction :
The construction of a plate and frame filter press is shown in the figure2. The filter
press is made of two types of units, plates and frames.
a) Frame—maintains the slurry reservoir, inlet (eye) for slurry.
b) Filter medium
c) Plate along with section-supports the filter medium, receiving the filtrate and
outlet
d) Assembly of plate and frame filter press
These are usually made of aluminium alloy. Sometimes these are also lacquered
for protection against corrosive chemicals and made suitable for steam sterilisation.
Frame contains an open space inside wherein the slurry reservoir is maintained for
filtration and an inlet to receive the slurry. It is indicated by two dots in the
description. The plate has a studded or grooved surface to support the filter cloth
and an outlet. It is indicated by one dot in the description. The filter medium
(usually cloth) is interposed between plate and frame. Frames of different
thicknesses are available. It is selected based on the thickness of the cake formed
during filtration. Optimum thickness of the frame should be chosen. Plate, filter
medium, frame, filter medium and plate are arranged in the sequence and clamped
to a supporting structure. It is normally described by dots as 1.2.1.2.1 so on. A
number of plates and frames are employed so that filtration area is a large as
necessary. In other words, a number of filtration units are operated in parallel.
Channels for the slurry inlet and filtrate outlet can be arranged by fitting eyes to the
plates and frames, these join together to form a channel. In some types, only one
inlet channel is formed, while each plate is having individual outlets controlled by
valves.
Working :
The working of the frame and plate process can be described in two steps, namely
filtration and washing of the cake (if desirable).
Filtration operation :
The working of a plate and frame press is shown in Figure. Slurry enters the frame
(marked by 2 dots) from the feed channel and passes through the filter medium on
to the surface of the plate (marked by I dot). The solids form a filter cake and
remain in the frame. The thickness of the cake is half of the frame thickness,
because on each side of the frame filtration occur. Thus, two filter cakes are
formed, which meet eventually in the centre of the frame. In general, there will be
an optimum thickness of filter cake for any slurry, depending on the solid content
in the slurry and the resistance -of the
filter cake.
The filtrate drains between the projections on the surface of the plate and escapes
from the outlet. As filtration proceeds, the resistance of the cake increase and the
filtration rate decreases. At a certain point, is preferable to stop the process rather
than continuing at very low flow rates. The press is emptied and the cycle is
restarted.
Washing operation:
If it is necessary to wash the filter cake, the ordinary plate and frame press is
unsatisfactory. Two cakes are built up in the frame meeting eventually in the
middle. This means that flow is brought virtually to a stand still. Hence, water
wash using the same channels of the filtrate is very inefficient, if not impossible.
A modification of the plate and frame press is used. For this purpose, an additional
channel is included (Figure). These wash plates are identified by three dots. In half
the wash plate there is a connection from the wash water channel to the surface of
the plate.
The sequence of arrangement of plates and frames can be represented by dots as
1.2.3.2.1.2.3.2.1.2.3.2.1 so on (between I and 1,2.3.2 must be arranged).
Special provisions:
(I) Any possible contamination can be observed by passing the filtrate through a
glass tube or sight glass from the outlet on each plate. This permits the inspection
of quality of the filtrate. The filtrate goes through the control valve to an outlet
channel.
(2) The filtration process from each plate can be seen. In the event of a broken
cloth, the faulty plate can be isolated and filtration can be continued with one plate
less.

Uses :
Filter sheets composed of asbestos and cellulose are capable of retaining bacteria,
so that sterile filtrate can be obtained, provided that the whole filter press and filter
medium have been previously sterilized. Usually steam is passed through the
assembled unit for sterilization.
Examples include collection of precipitated antitoxin, removal of precipitated
proteins from insulin liquors and removal of cell broth from the fermentation
medium.
Heating/cooling coils are incorporated in the press so as to make it suitable for the
filtration of viscous liquids .
Advantages :
(1) Construction of filter press is very simple and a variety of materials can be
used.
– Cast iron for handling common substances.
— Bronze for smaller units.
– Stainless steel is used there by contamination can be avoided.
– Hard rubber or plastics where metal must be avoided.
– Wood for lightness though it must be kept wet.
(2) It provides a large filtering area in a relatively small floor space. It is versatile,
the capacity being variable according to the thickness of frames and the number
used. Surface area can be increased by employing chambers up to 60.
(3) The sturdy construction permits the use of considerable pressure difference.
About 2000 kilopascals can’ be normally used.
(4) Efficient washing of the cake is possible.
(5) Operation and maintenance is straight forward, because there are no moving
parts, filter cloths are easily renewable. Since all joints are external, a plate can be
disconnected if any leaks are visible. Thus contamination of the filtrate can be
avoided.
(6) It produces dry cake in the form of slab.
Disadvantages :
(I)it is a batch filters so there is a good deal of ‘down-time’, which is non-
productive.
(2) The filter press is an expensive filter. The emptying time, the labour involved
and the wear and tear of the cloth resulting in high costs.
(3)operation is critical, as the frames should be full, otherwise washing is
inefficient and the cake is difficult to remove.
(4) The filter press is used for slurries containing less than 5% solids. So high
costs make it imperative that this filter press is used for expensive materials.
Examples include the collection of precipitated antitoxin and removal of
precipitated proteins from insulin liquors.
Disc filters:
The term disc filter is applied to assemblies of felt or paper discs sealed into a
pressure case.
Construction:
The discs may be pre-assembled into a self-supporting unit, or each disc may rest
on an individual screen or plate. Single plate or multiples of single plates may be
applied. The flow may be inside out wards or outside inwards.
Advantages:
i. Compactness
ii. Portability
iii. Cleanliness
 MEMBRANE FILTERS:
These are plastic membranes based on cellulose acetate, cellulose nitrate or mixed
cellulose esters with pore sizes in the micron or submicron range. They are very
thin (about 120 micron thick) and must be handled carefully. They act like a sieve
trapping particulate matter on their surface.
Several grades of filters are available with pore sizes ranging from 0.010 ± 0.002
micron to 5.0 ± 1.2 micron. Type codes VF and SM are given by Millipore Filter
Corp. for
these two extreme ranges respectively.
Filters with pore sizes from 0.010 to 0.10 micron can remove virus particles from
water or air. Filters with pore sizes from 0.30 to 0.65 microns are employed for
removing bacteria. Filters with the larger pore sizes, viz. 0.8, 1.2 and 3.0 to 5.0
microns are employed, for example, in aerosol, radio activity and particle sizing
applications.
During use membrane filters are supported on a rigid base of perforated metal,
plastic or coarse sintered glass as in the case of fibrous pad filters. If the solution to
be filtered contains a considerable quantity of suspended matter, preliminary
filtration through a suitable depth filter avoids clogging of the membrane filter
during sterile filtration. They are brittle when dry and can be stored indefinitely in
the dry state but are fairly tough when wet.
ADVANTAGES:
i. No bacterial growth through the filter takes place during prolonged filtration.
ii. They are disposable and hence no cross contamination takes place.
iii. Adsorption is negligible they yield no fibres or alkali into the filterate.
Filtration rate is rapid.

DISADVANTAGES:
i. They may clog though rarely.
ii. Ordinary types are less resistant to solvents like chloroform
Cartridge Filters:
Cartridge filters have an integral cylindric configuration made with disposable or
cleanable filter media and utilize either plastic or metal structural hardware.26
With the discovery of strong pleat-able membranes such as cellulose nitrate,
polyamide, polyvinylidene chloride, PTFE, and nylon, cartridge filters have
revolutionized the filtration industry. Cartridge filters provide maximum filtration
area in the smallest possible package, allow quick changeout of the media, and
save time and money. Cartridge filters of different shapes, structures, forms, and
sizes for. different applications in the pharmaceutical industry are now available in
disposable and non-disposable forms. The housings for cartridge filters come in a
wide variety of configurations for both micron and submicron filtration. The major
differences in various housings are in the design, materials of construction, seals
that are used to install the cartridge in the housing, and the application for which
they are used in the pharmaceutical industry. The housing for cartridge filters are
described in terms of the height of the cartridge and in the number of cartridge
receptacles in the base end of the housing. When a user purchases a housing from
one manufacturer, he is usually not “locked in” to that manufacturer’s cartridges.
Adaptors are available that allow the cartridge filter of one manufacturer to fit into
virtually any other manufacturer’s housing. Filter media can be formed into
cartridge form by either tubular-wound, string-wound, or pleated formation.
Alternate layers of filter media and separator material are rolled into a spiral
configuration, and by potting the ends of the cartridge, form the “dead-ended” or
“cross- flow” type of flow channels. String-wound cartridges are the most
commonly used and inexpensive filters available. Pleated cartridges are modified
tubular configurations with a large filtration area. A single knife-edge flat gasket
may be a satisfactory seal for cartridge filters with 1.0-micron or larger pore size.
For submicron filtration, the most satisfactory seal is an O-ring. Disposable or
permanent cartridge filters are used for fluid clarification or sterilization. Standard
elements for nonsterile filtration may be interchanged between cartridge holders
offered by several companies. Increases in capacity result from multi-element
holders, and 12 element units are usually adequate for batches of 500 to 1000
gallons. The cost of dis¬ posable elements is offset by labour savings inherent in
the simplicity of assembly and cleaning of cartridge clarifiers. The metallic edge
filters, particularly those with self-cleaning devices, are excel¬ lent security filters
for suspensions that may plug or blind conventional Wire mesh. A cleaning blade
combs away accumulated solids, which fall into a sump in the filter casing. A
quick-coupling metal cartridge filter with construction that prevents short
circuiting of the filter element is also available. The special design permits rapid
disassembly as well as interchange of reusable filter media. Metal elements permit
particle retention as low as 1.5 microns. Duo filters, two units connected in
parallel, are recommended where uninterrupted service is required. A high-
frequency vibrator, acting only on the element, assists in filtration of slurries that
have blinding tendencies. Vendor^ of membrane filters offer cartridge units in
single- and multiple-element configurations. These cartridges have become the unit
of choice for high-volume, sterile filtrations and are ideal for in-line, final polish
prior to bottling of bulk parenterals. Cartridge filters having absolute ratings of
0.04 microns are also avail¬ able (Fig. 7-19). The latter units have 5 to 10 square
feet of effective filtering area per cartridge of 10-inch height, and some can also be
steam-sterilized.
Centrifugation filtration and sedimentation:
Filtering centrifuges and centrifugal sedimentors are another general class of solids
recovery devices.
Filtering centrifuges:
In filtering centrifuges, centrifugal force is used to affect the passage of the liquid
through the filter medium. This type of filtration is advantageous when very fine
particles are involved. Whenever solid recovery is the primary goal, filtering
centrifuges must be considered as an alternative to filtration.
Centrifugal sedimentors:
In centrifugal sedimentors, the separation is due to the difference in the density of
two or more phases.
Use:
Centrifugal sedimentors are used for complete separation of solid-liquid mixtures
and liquid-liquid mixtures.
Perforated basket:

Construction:
The device consists of a perforated metal basket mounted on a vertical axis by
means of which it can be rotated at a speed of 20—25 revolutions per second.
The cloth used to retain solids is often supported on a metal screen and the outer
casing collects the liquid thrown out from the perforated basket by centrifugal
force.
Operation:
Baskets mounted are emptied by shoveling the cake. If, however, top suspension is
used, the cake can be more easily withdrawn through the traps in the base of the
basket. In batch operation, considerable time is lost during machine acceleration
and deceleration.
Use:
Machines operating with continuous discharge of solids are used for separating
coarse solids during large-scale operations. Such machines are commonly
constructed with a horizontal axis of rotation.
Tubular bowl centrifuge:
It is the Sharples super-centrifuge.
Operation speed:
It operated at up to 15,000 rpm, or in turbine-driven laboratory models, up to
50,000 rpm.

Length to diameter ratio:

For operation at a very high speeds, the centrifuge bowl is tubular with a length to
diameter ratio from 4 to 8.
Use:
i. It is widely used in emulsion separation.
ii. Cleaning fats and waxes
iii. Blood fractionation
iv. Virus recovery
Conical disc type centrifuges:
Construction:
It consists of a series of conical discs into the bowl.
Length to diameter ratio:
The length to diameter ratio is much smaller
than in tubular bowl centrifuges and
operational speeds are lower.
Operation:
The feed enters through a centric tube
surrounding the central drive shaft and flows
into the spaces between the disc. As, the
centrifuge rotates, the heavier liquid or solid
moves underside and the lighter liquid moves
to the upper side of the discs. Small operating
distance, i.e. only the space between the discs,
increases the efficiency of the equipment.
Horizontal continuous centrifuge:
These are preferred when higher proportions of solids are involved.
Construction:
It consists of a conical bowl, mounted horizontally.
Operation:
The slurry is introduced through the shaft and liquid separates to the wider portion
of the bowl. In continuous models, a conveying scroll, operating at a slightly
different speed from the basket, plows the solids one end and discharge the
material as a damp powder.
These centrifuges are capable of handling solids with a wide particle size range and
in slurries with concentration ranging from 0.5 to 50%.
Filters used in pharmaceutical industry:
1. Membrane filters
2. Filter leaf
3. Filter press
4. Filter candles
5. Meta filters
All discussed above.
Q.3 Define compression, compaction and consolidation of powdered solids.
Explain the solid-Air interface, angle of repose and compressibility index.
Compaction of powders is the general term used to describe the situation in which
these materials are subjected to some level of mechanical force. In the
pharmaceutical industries, the effects of such forces are particularly important in
the manufacturing of tablets and granules, in the filling of hard-shell gelatin
capsules, and in powder handling in general.
The physics of compaction may be simply sated as “the compression and
consolidation of a two- phases (particularly solid-gas) system due to applied
force”. Compression means a reduction in the bulk volume of the material as a
result of displacement of the gaseous phase. Consolidation is an increase in the
mechanical strength of the material as the resulting from the particle/ particle
interactions”. Before each of these simultaneous processes is discussed in more
detail, brief consideration is given to certain inherent properties of all the powdered
solids, which contribute to the characteristics of interest. In addition some derived
parameters that facilitate quantification of important variables are described.
The solid-Air Interface:
Atoms or ions are located at the surface of any solid particle are exposed to a
different distribution of intramolecular and intermolecular bonding forces than
those within the particle. As indicated in fig, they may be envisaged as unsatisfied
attractive molecular forces extending out some small distance beyond the solid
surface. The condition gives rise to what is called the free surface energy of the
solid, which plays a major role in the interaction between particles, and between
particles and its environment. Many important phenomena such as adsorption,
cohesion and adhesion, rate of solution, and crystallization are manifestations of
this fundamental property of all solids.
Because of these unsatisfied bonding forces at the surface of particles, those that
approach each other closely enough are inherently attracted and tend to stick to one
another. This attraction between like particles is called cohesion. In addition, when
they approach other types of particles or solid surfaces, they are attracted to them,
leading to what is termed adhesion. These attractions give rise to an intrinsic
property of all bulk powdered solids: they resist differential movement of their
constituent particles when subjected to external forces. This phenomena has
important influence on several operations, such as flow from hoppers or feeders,
relative motion in mixers and compression to produce granules or tablets.
The overall resistance to relative movement of particles may be markedly
affected by two other factors.
i. First, many powders of pharmaceutical interest readily develop electrostatic
forces, especially when subjected to internal friction, although particles
particle contact and separation are the only prerequisite. The charge
developed depends on the particular material involved and the type of
motion produced in it. Usually, electrostatic forces are relatively small, but
may be significant because they act over a greater distance than the
molecular forces.
ii. The second factor, namely the presence of an adsorbed layer of moisture on
particles, reduces the chance of any complicating electrostatic effect by
providing a conducting path for charge dissipation. When particles approach
one another closely enough, however, these films of moisture can form
 liquid bridges, which holds the particles together by surface tension effects
and by a negative capillary pressure.
Angle of Repose:
Although the contributions of each of these effects cannot always be distinguished,
there are relatively simple practical techniques for measuring resistance to particle
movement. For example, a quantity called the angle of repose of a powder can be
determined. This is the angle 𝝫 as described by the equation.

It is the maximum angle that can be obtained between the freestanding surface of a
powder heap and the horizontal plane, as shown in figure. Such measurements give
at least a qualitative assessment of the internal cohesive and frictional effects under
low levels of external loading, as might apply in powder mixing, or in tablet die or
capsule shell filing operations.
Angle of repose methods, which results in a so called dynamic angle, are preferred,
since they most closely mimic the manufacturing situation, in which the powder is
in motion.
A typical dynamic test involves a hollow cylinder half-filled with the test powder,
with one end sealed by a transparent plate. The cylinder is rotated about its
horizontal axis (fig), until the powder surface cascades. The curved wall is lined
with sandpaper to prevent preferential slip at this surface. In a second method, a
sandpaper-lined rectangular box is filled with the powder and carefully tilted until
the contents begin to slide, as shown in fig. values of are rarely less than 20○ ,
and values of up to 40○ indicated reasonable flow potential. Above 50○, however,
the powder flows only with great difficulty, it at all.
With care, dynamic angle of repose measurements can be replicated with relative
standard deviations of approximately 2%. They are particularly sensitive to
changes in particle size distribution and to moisture content, and they provide a
rapid means of monitoring significant batch to batch differences in these respects.
Flow rates:
Alternatively, resistance to movement of particles, especially for granular powders
with little cohesiveness, may be assessed by determining their flow rate Q through
a circular orifice (a tablet die, for instance) fitted in the base of cylindric container.
Flow experiments with mixtures of different size fractions of the same material can
be particularly valuable, because in many instances, there exist optimum
proportions that lead to a maximum flow rate, as shown in figure. Note that for this
system, when the proportion of fine particles exceed approximately 40%, there is
dramatic fall in the flow rate.
Compressibility index:
A simple indication of the ease with which a material can be induced to flow is
given by application of compressibility index (1) given by equation:

Where V is the volume occupied by the sample of the powder after being subjected
to a standardized tapping procedure, and V○ is the volume before tapping. Value of
I below 15% usually give rise to good flow characteristics, but reading above 25%
indicated poor flowability.
Q.4 What is the mass-volume relationship? Explain the different practical
techniques for measuring the volume of powder samples.
Mass- volume relationships:
Mass:
The mass is how much it resists acceleration when a force is applied to it and
generally means how much of an object or substance there is.
Volume:
Volume describes how much space an object takes up. These quantities can be
used in determining pressure, temperature and other features of gases, solids and
liquids.
Volume
Although the mass of a bulk powder sample can be determined with great
accuracy, measurement of the volume is more complicated than it may first appear.
The ,main problem arises in actually defining volumes of bulk powders,
1. Open intraparticulate voids-those within a single particle but open to the
external environment.
2. Closed intraparticulate voids-those within a single but closed to the external
environment.
3. Intraparticulate voids-the air spaces between individual particles.
Therefore at least three interpretations of powder volume may be proposed:
1. The true volume (vt) the total volume of the solid particles, which excludes all
spaces greater than molecular dimensions, and which has a characteristic value for
each material.
2. The granular volume (particle volume)(vg)-the commulative volume occupied
by the particles, including all intra-particulate (but not inter-particulate) voids. The
boundary between open intra-particulate and inter-particulate air spaces may be
interpreted differently, so that this interpretation of the volume depends on the
method of measurement.
3. The bulk volume(vb)-the total volume occupied by the entire powder mass
under the particular packing achieved during the measurement. Thus, this
interpretation also depends on method. when studying phenomena resulting in a
change in volume, it may be convenient to consider the volume v of the sample
under specific experimental conditions, relative to the true volume v t. A useful
dimensionless quantity relative volume vr may be defined as:
Vr = v/vt
The relative volume decreases and tends toward unity as all the air is eliminated
from the mass.
This phenomenon occurs in the compressional processes such as tableting.
The voids present in the powder mass be more significant than the solid
components in certain studies. For example, a fine capillary network of voids or
pores has been shown to enhance the rate of liquid uptake by tablets, which in turn
increases the rate of their disintegration. For this reason, a second dimensionless
quantity, the ratio of the total volume of void spaces (vv) to the bulk volume of the
material, is often selected to monitor the progress of compression. The ratio vv/vb
is reffered to as the porosity (E) of the material:
Vv = vb - vt
Therefore : porosity E = vb - vt/vb = 1 - vt/vb
Porosity is frequently expressed as a percentage:
E = 100 . [1 - vt/vb]
Different practical techniques for measuring the volume of powder samples:
BULK DENSITY:
The bulk density of a powder is the ratio of the mass of an untapped powder
sample and its volume including the contribution of the inter-particulate void
volume. Hence, the bulk density depends on both the density of powder particles
and the spatial arrangement of particles in the powder bed. The bulk density is
expressed in grams per millilitre (g/ml) although the international unit is kilogram
per cubic metre (1 g/ml = 1000 kg/m3 ) because the measurements are made using
cylinders.
It may also be expressed in grams per cubic centimetre (g/cm3 ).
The bulking properties of a powder are dependent upon the preparation, treatment
and storage of the sample, i.e. how it was handled. The particles can be packed to
have a range of bulk densities and, moreover, the slightest disturbance of the
powder bed may result in a changed bulk density. Thus, the bulk density of a
powder is often very.
The bulk density of a powder is determined by measuring the volume of a known
mass of powder sample, that may have been passed through a sieve, into a
graduated cylinder (Method A), or by measuring the mass of a known volume of
powder that has been passed through a volumeter into a cup (Method B) or a
measuring vessel (Method C).
Method A and Method C are favoured.
Method A. Measurement in a graduated cylinder
Procedure.
Pass a quantity of powder sufficient to
complete the test through a sieve with
apertures greater than or equal to 1.0 mm, if
necessary, to break up agglomerates that may
have formed during storage; this must be done
gently to avoid changing the nature of the
material. Into a dry graduated cylinder of 250
ml (readable to 2 ml), gently introduce, without
compacting, approximately 100 g of the test
sample (m) weighed with 0.1% accuracy.
Carefully level the powder without
compacting, if necessary, and read the
unsettled apparent volume (V0) to the nearest
graduated unit. Calculate the bulk density in
(g/ml) using the formula m/V0. Generally,
replicate determinations are desirable for the
determination of this property.
If the powder density is too low or too high, such that the test sample has an
untapped apparent volume of either more than 250 ml or less than 150 ml, it is not
possible to use 100 g of powder sample. Therefore, a different amount of powder
has to be selected as test sample, such that its untapped apparent volume is 150 ml
to 250 ml (apparent volume greater than or equal to 60% of the total volume of the
cylinder); the mass of the test sample is specified in the expression of results.
For test samples having an apparent volume between 50 ml and 100 ml a 100 ml
cylinder readable to 1 ml can be used; the volume of the cylinder is specified in the
expression of results.
Method B. Measurement in a volumeter Apparatus.
The apparatus consists of a top funnel fitted with a 1.0 mm sieve. The funnel is
mounted over a baffle box containing four glass baffle plates over which the
powder slides and bounces as it passes. At the bottom of the baffle box is a funnel
that collects the powder and allows it to pour into a cup mounted directly below it.
The cup may be cylindrical (25.00 ± 0.05 ml volume with an inside diameter of
30.00 ± 2.00 mm) or cubical (16.39 ± 0.20 ml volume with inside dimensions of
25.400 ± 0.076 mm).
Procedure. Allow an excess of powder to flow through the apparatus into the
sample receiving cup until it overflows, using a minimum of 25 cm3 of powder
with the cubical cup and 35 cm3 of powder with the cylindrical cup. Carefully,
scrape excess powder from the top of the cup by smoothly moving the edge of the
blade of a spatula perpendicular to and in contact with the top surface of the cup,
taking care to keep the spatula perpendicular to prevent packing or removal of
powder from the cup. Remove any material from the side of the cup and determine
the mass (M) of the powder to the nearest 0.1%. Calculate the bulk density (g/ml)
using the formula M/V0 in which V0 is the volume of the cup and record the
average of three determinations using three different powder samples.
Procedure. Pass a quantity of powder sufficient to complete the test through a 1.0
mm sieve, if necessary, to break up agglomerates that may have formed during
storage and allow the obtained sample to flow freely into the measuring vessel
until it overflows. Carefully scrape the excess powder from the top of the vessel as
described for Method B. Determine the mass (M0) of the powder to the nearest
0.1% by subtraction of the previously determined mass of the empty measuring
vessel. Calculate the bulk density (g/ml) using the formula M0/100 and record the
average of three determinations using three different powder samples.
TAPPED DENSITY:
The tapped density is an increased bulk density attained after mechanically
tapping a container containing the powder sample. The tapped density is obtained
by mechanically tapping a graduated measuring cylinder or vessel containing the
powder sample. After observing the initial powder volume or mass, the measuring
cylinder or vessel is mechanically tapped, and volume or mass readings are taken
until little further volume or mass change is observed. The mechanical tapping is
achieved by raising the cylinder or vessel and allowing it to drop, under its own
mass, a specified distance by either of three methods as described below. Devices
that rotate the cylinder or vessel during tapping may be preferred to minimize any
possible separation of the mass during tapping down.
Method A:
Apparatus. The apparatus (Figure 3) consists of the following: — a 250 ml
graduated cylinder (readable to 2 ml) with a mass of 220 ± 44 g; and — a settling
apparatus capable of producing, in 1 minute, either nominally 250 ± 15 taps from a
height of 3 ± 0.2 mm, or nominally 300 ± 15 taps from a height of 14 ± 2 mm. The
support for the graduated cylinder, with its holder, has a mass of 450 ± 10 g.
Procedure.
Proceed as described above for the determination of the bulk volume (V0). Secure
the cylinder in the holder. Carry out 10, 500 and 1250 taps on the same powder
sample and read the corresponding volumes V10, V500 and V1250 to the nearest
graduated unit. If the difference between V500 and V1250 is less than or equal to 2
ml, V1250 is the tapped volume. If the difference between V500 and V1250
exceeds 2 ml, repeat in increments such as 1250 taps, until the difference between
succeeding measurements is less than or equal to 2 ml. Fewer taps may be
appropriate for some powders, when validated. Calculate the tapped density (g/ml)
using the formula m/Vf in which Vf is the final tapped volume. Generally,
replicate determinations are desirable for the determination of this property.
Specify the drop height with the results. If it is not possible to use a 100 g test
sample, use a reduced amount and a suitable 100 ml graduated cylinder (readable
to 1 ml) weighing 130 ± 16 g and mounted on a holder weighing 240 ± 12 g. The
modified test conditions are specified in the expression of the results.
Method B:
Procedure.
Proceed as directed under Method A except that the mechanical tester provides a
fixed drop of 3 ± 0.2 mm at a nominal rate of 250 taps per minute. Method C:
Procedure. Proceed as described in Method C for measuring the bulk density using
the measuring vessel equipped with the cap shown in Figure 2. The measuring
vessel with the cap is lifted 50-60 times per minute by the use of a suitable tapped
density tester. Carry out 200 taps, remove the cap and carefully scrape excess
powder from the top of the measuring vessel as described in Method C for
measuring the bulk density. Repeat the procedure using 400 taps. If the difference
between the two masses obtained after 200 and 400 taps exceeds 2%, carry out a
test using 200 additional taps until the difference between succeeding
measurements is less than 2%. Calculate the tapped density (g/ml) using the
formula Mf/100 where Mf is the mass of powder in the measuring vessel. Record
the average of three determinations using three different powder samples. The test
conditions including tapping height are specified in the expression of the results.
specific gravity bottle method (Pycnometry):
procedure:
A pycnometer is a vessel with a precisely known volume. When one thinks of
density determinations, one usually thinks of a pycnometer. Although a
pycnometer is used to determine density ρ or specific gravity, it measures volume
V; a balance is used to determine mass m. Manual pycnometers (glassware)
typically are used to determine the density or specific gravity of liquids by filling
the vessel, then weighing. Density is calculated by ρ = m/V and specific gravity by
the same equation and dividing both sides by the density of water with reference to
temperature. Essentially the same process can be used to determine the volume of
an unknown, enclosed space. First the object containing the void is weighed empty.
It is then filled with a liquid of known density and reweighed. The weight
difference ∆m is the weight of the liquid and from these data, volume can be
calculated by V = ∆m/ρ. As will be explained, this process is used to ‘calibrate’
sample cells used in mercury porosimetry. Another pycnometer method is to place
a quantity of a dry, pre-weighed solid sample in the pycnometer and fill the rest of
the pycnometer with a liquid of known density (typically water), the weight of the
pycnometer filled only with the liquid having previously been established. The
density of the sample can be determined from the known density of the water, the
weight of the pycnometer filled only with the liquid, the weight of the pycnometer
containing both sample and liquid, and the weight of the sample. This is a common
method used in characterizing soil samples.
Helium pycnometer method:
Several practical techniques axe available for measuring the volume of powder
samples. Apart from x-ray diffraction methods, the nearest approach to true
volume is probably provided by a helium pycnometer. This works on the principle
that within a sealed system containing helium (a nonadsorbing gas), the change in
pressure caused by a finite change in volume of the system is a function of its total
volume. A schematic diagram for a typical apparatus is following. During
operation, the volume of the system is varied by means of the piston until a pre¬
set constant pressure is produced. This pressure is indicated by the sealed bellows
pressure detector, which incorporates an integral electrical contact. The piston
movement (U) necessary to achieve this pressure is read off from the scale. This
value depends on the total volume of the system, which in turn is a function of the
sample volume in the cell. The pycnometer is first calibrated using a sample of
known volume vc (usually a stainless steel sphere). The operating equation for the
instrument then becomes:
where Uj, U2 and Us are the variable volume scale readings for an empty cell, with
standard volume, and with test powder, respectively. Alternatively in some
instances, a large com¬ pact of the material can be prepared at high compressional
force (therefore assuming zero porosity). Then, by accurately measuring its overall
dimensions, true volume can be calculated. Liquid displacement by a powder
pycnometer (specific gravity bottle method) can also be used, but unless special
precautions are taken to ensure that no air remains in the sample, the results are
prone to errors. For this reason, liquid displacement is probably best regarded as a
measurement of granule volume, especially if liquids that do not readily wet the
powder are used, e.g., certain inert organic liquids, or mercury.
Q.5.What is the effect of applied forces? Explain the deformation,
compression and consolidation of powder solids.
EFFECTS OF APPLIED FORCES:
Applied force:
An applied force is a force that is applied to an object by a person or another
object. If a person is pushing a desk across the room, then there is an applied
force acting upon the object. The applied force is the force exerted on the desk by
the person.
Some of the effects of applied forces on the material are deformation, compression,
consolidation and compaction.
Deformation:
“ The change in the shape or size of an object through the application
of external forces is known as deformation.”
✓ When any solid body is subjected to opposing forces, there is a finite change
in its geometry depending upon the nature of the applied load. The relative
amount of deformation produced by such forces is a dimensionless quantity
called as strain.
 Three commonest kinds of strain are illustrated below:

The above diagrams show change in the geometry[strain] of a solid body resulting
from various types of applied forces i.e Tensile strain[a], Compressive strain[b]
and Shear strain[c].
For example, if a solid rod is compressed by forces acting at each end to cause a
reduction in length of ∆H from an unloaded length of H˳ then the Compressive
strain Z is given as:
Z = ∆H / H˳
The ratio of the force F necessary to produce this strain to the area A over which it
acts is called the stress б that is:
б = F/A
Because most powder masses contain some air spaces, true analogous behavior to a
solid body should not be expected. Nevertheless, under low porosity conditions
[high applied forces] comparisons provide a useful way of interpreting
experimental observations.
Compression:
“ Compression means a reduction in the bulk volume of the
material as a result of displacement of the gaseous phase.”
When external mechanical forces are applied to a powder mass, there is normally a
reduction in its bulk volume as a result of one or more of the following effects. The
onset of loading is usually accompanied by closer repacking of the powder
particles and in most cases, this is main mechanism of initial volume reduction as
shown in figure:
 FIGURE: Effects of compressional force on a bed of powder
As the load increases, rearrangement becomes more difficult and further
compression involves some type of particle deformation. If on removal of the
load, the deformation is to a large extent spontaneously reversible i.e if it behaves
like rubber, then the deformation is said to be elastic. All solids undergo some
elastic deformation when subjected to external forces. With several pharmaceutical
materials, such as acetylsalicylic acid and microcrystalline cellulose, elastic
deformation becomes the dominant mechanism of compression within the range of
maximum forces normally encountered in practice.
In other groups of powdered solids, an elastic limit or yield point is reached and
loads above this level result in deformation but the deformation is not immediately
reversible on removal of the applied force. In these cases, bulk volume reduction
results from plastic deformation or viscous flow of the particles which are
squeezed into the remaining void spaces, resembling the behavior of modeling
clay. This mechanism predominates in materials in which the shear strength is less
than the tensile or breaking strength. Conversely, when the shear strength is
greater, particles may be fractured and the smaller fragments then help to fill up
any adjacent air space. This is most likely to occur with hard, brittle particles and is
known as brittle fracture. For example, Sucrose behaves in this manner.
Irrespective of the behavior of large particles of the material, small particles may
deform plastically, a process known as Microsquashing. The proportion of the fine
powder in a sample may therefore be significant. Highly irregular particles could
also behave in this way, thus particle shape is another important factor.
The above account describes all the possible mechanisms that can contribute to the
reduction in bulk volume of powder bed, when subjected to external mechanical
forces. All of the deformation effects may be accompanied by the breaking and
formation of new bonds between the particles, which give rise to consolidation as
the new surfaces are pressed together.
The packaging of bulk powders and the filling of hard gelatin capsules mostly
involve bulk volume reductions achieved by repacking and mimimal amount of
deformation. On other hand, in the Tableting process or in specialized techniques
as Roll compacting or extruding- [which involves high levels of compressive
force]- repacking,elastic deformation, plastic deformation and brittle fracture may
all takes place.
Consolidation:
“Consolidation is an increase in the mechanical strength of the
material resulting from particle-particle interactions.”
When the surfaces of two particles approach each other closely enough [e.g at a
separation of less than 50nm] their free surface energies result in a strong attractive
force, a process known as cold welding.
The nature of the bonds so formed are similar to those of the molecular structure of
the interior of the particles, but because of the roughness of the particle surface ,the
actual surface area involved may be small. This hypothesis is favoured as a major
reason for the increasing mechanical strength of powder bed when subjected to
compressive forces.
On the macroscale, most particles encountered in practice have an irregular shape,
so that there are many points of contact in a bed of powder. Any applied load to the
bed must be transmitted through these particle contact under appreciable forces,
this transmission may result in generation of considerable frictional heat. If this
heat is not dissipated, the local rise in temperature could be sufficient to cause
melting of the contact area of the particles ,which would relieve the stress in that
particular region. In this case the melt solidifies, giving rise to fusion bonding.
This in turns results in an increase in mechanical strength of the mass.
Many pharmaceutical solids possess a low specific heat and poor thermal
conductivity. So the heat transfer away from the contact points is slow. In both
cold and fusion welding, the process is influenced by several factors:
✓ The chemical nature of the materials
✓ The extent of the available surface
✓ The presence of surface contaminants
✓ The intersurface distances
The type and degree of crystallinity in a particular material influences its
consolidative behavior under appreciable applied force. An example is that the
substances possessing the “cubic lattice arrangement” were tabletted more
satisfactorily than those with a “rhombohedral lattice”.
The particles of most pharmaceutical powders consist of small crystallites or
grains aggregated in a random manner, so that their crystal planes are not aligned
with one another. Such an arrangement adds to the material’s resistance to plastic
deformation. For example, of the two chemically similar organic materials
methacetin and phenacetin, apparently only the former can be tabletted without
the tendency to laminate. More importantly, different polymorphic forms and
crystal habits of the same compound may not behave in the same way in terms of
compaction properties.