Industrial pharmacy complete notes Pharm D. 4th professional

1. GHULAM MURTAZA HAMAD
FOURTH PROFF EVENING | PUNJAB UNIVERSITY COLLEGE OF PHARMACY, LAHORE
INDUSTRIAL
PHARMACY
4TH
PROFESSIONAL
Reference
Lachman and Lieberman- The
Theory and Practice of
Industrial Pharmacy, 5th
Edition
Aulton's Pharmaceutics- The
Design and Manufacture of
Medicines, 4th
Edition
Martin’s Physical Pharmacy
and Pharmaceutical Sciences,
5th
Edition

2. GM Hamad
TABLE OF CONTENTS
Contents
1. Mass Transfer
2. Heat Transfer
3. Drying
4. Comminution (Size Reduction)
5. Mixing
6. Clarification and Filtration
7. Evaporation
8. Compression and Compaction
9. Safety Methods in Pharmaceutical Industry
10. Emulsions
11. Suspensions
12. Semisolids
13. Sterile Products
14. Packing and Packaging

3. GM Hamad
MASS TRANSFER
INTRODUCTION
• It includes the transfer of mass from a solid to a fluid and from a fluid to
fluid which emphasis on the effect of boundary layer and influence of
mass transfer phenomenon on the unit operation.
• Three fundamental transfer processes:
- Momentum transfer
- Heat transfer
- Mass transfer
• Mass transfer may occur in a gas mixture, a liquid solution or solid. Mass
transfer occurs whenever there is a gradient in the concentration of a
species. The basic mechanisms are the same whether the phase is a gas,
liquid, or solid. It usually occurs due to diffusion.
MODES OF MASS TRANSFER
• The two modes of mass transfer:
- Molecular diffusion
- Convective mass transfer
1. MOLECULAR DIFFUSION
• The diffusion of molecules is when the whole bulk fluid is not moving but
stationary. Diffusion of molecules is due to a concentration gradient.
A. FICK’S LAW
- Linear relation between the rate of diffusion of chemical species and
the concentration gradient of that species. The general Fick’s law
Equation for binary mixture of A and B is:
𝐽 𝐴
°
= − 𝑐𝐷𝐴𝐵
𝑑𝑥 𝐴
𝑑𝑧
B. THERMAL DIFFUSION
- Diffusion due to a temperature gradient. Usually negligible unless
the temperature gradient is very large.
C. PRESSURE DIFFUSION
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- Diffusion due to a pressure gradient. Usually negligible unless the
pressure gradient is very large.
D. FORCED DIFFUSION
- Diffusion due to external force field acting on a molecule. Forced
diffusion occurs when an external field is imposed on an electrolyte
(for example, in charging an automobile battery)
E. KNUDSEN DIFFUSION
- Diffusion phenomena occur in porous solids.
2. CONVECTION MASS TRANSFER
• When a fluid flowing outside a solid surface in forced convection motion,
rate of convective mass transfer is given by:
𝑁A = 𝑘 𝑐(𝐶𝐿𝐼 − 𝐶𝐿𝑖)
- Where, Kc = mass transfer coefficient, CLi = bulk fluid
concentration, CLI = conc. of fluid near the solid surface
• Kc depends on:
i. System Geometry
ii. Fluid properties
iii. Flow velocity
• Whenever there is concentration difference in a medium, nature tends
to equalize things by forcing a flow from the high to the low
concentration region. The molecular transport process of mass is
characterized by the general equation:
Rate of transfer process = driving force / resistance
TYPES OF MASS TRANSFER
• Different types of mass transfer are as follows:
1. SOLID- FLUID MASS TRANSFER
• Consider a crystal of soluble material immerged in solvent in which it is
dissolving. Where crystal is surrounded by a stationary boundary layer of
the solute with the bulk of fluid able to move. Such movement could be
natural convection arising from temperature or density changes or
forced convection resulting from agitation. Hence transport of the
molecules of dissolving solids will take place in 2 stages:
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I. First the molecules move through the boundary layer by molecular
diffusion with no mechanical mixing or movement process that is
analogous to heat transfer by conduction.
II. Secondary, once material has passed to the boundary layer mass
transfer takes place by bulk movement of solution known as eddy
diffusion. It is analogous to heat transfer by convection. Since there is
virtually no limit to vigorous movement of bulk of fluid.
• The controlling factor in the rate of crystal will be molecular diffusion
through the boundary layer. Eddy diffusion will not be considered
further. In general, molecular diffusion is the controlling process. Mass
transfer by this process can be represented in a similar manner to
conduction heat transfer but with a concentration gradient instead of
temperature gradient. Mass transfer by molecular diffusion can be
represented by an equation:
W =
DA (C1 − C2)
L
O
- Where, W = weight of solute diffusion, D = diffusion constant, A =
area, o = time, C1 = conc. of solute at interface, C2 = conc. of solute
in bulk, L = film thickness
2. SOLID-GAS MASS TRANSFER
• The term fluid includes gases and vapors as well as liquids and refer
equally to mass transfer from a solid to a gas. As an example of a solid is
drying in air to vapor molecule must be diffuse through the air boundary
layer to the atmosphere. The driving force in this case will be the partial
vapor pressure gradient through the air boundary layers.
W =
DA (P1 − P2)
L
O
- Where, W = weight of solute diffusion, D = diffusion constant, A =
area, o = time, P1 = partial pressure of vapor at interface, P2 =
partial pressure of vapor in atmosphere, L = film thickness
3. FLUID-FLUID MASS TRANSFER
• It occurs when mass transfer takes place between immiscible fluids.
Which may be two liquids or liquid and gas (vapor). In this case there will
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be boundary layer of fluids on each side of the interface where the slope
of concentration gradient depends on the diffusion co-efficient in two
materials as shown in figure, where slope of the concentration gradient
depends upon the diffusion coefficients in the two systems.
INFLUENCE ON UNIT OPERATION
• Mass transfer theory can be applied in any operation in which material
change phase. Where it is solid, liquid, vapor, liquid-liquid-vapor. The
effect can be seen in simple operation as making if a solution of a solid in
liquid where the rate of solution can be increases by different factors:
1. AGITATION
• It reduces the thickness of boundary layer and disperses any local
concentration of solution so increases the concentration gradient.
2. ELEVATED TEMPERATURE
• It will increase solubility of most materials but increase diffusion co-
efficient and decrease the viscosity of liquid so reduce the boundary layer
thickness.
3. SIZE REDUCTION OF SOLID
• It increases area over which diffusion can occur.
4. MASS TRANSFER EQUIPMENT
• Design of mass transfer equipment must confirm turbulent flow
conduction, maximum concentration of partial pressure gradient and
largest possible surface area.
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HEAT TRANSFER
DEFINITION
• Heat transfer is the study of exchange of thermal energy through a body
or between bodies which occurs when there is a temperature difference.
INTRODUCTION
• In pharmaceutical technology, in order to achieve a well-defined
technological purpose, heat is frequently transferred to some material
to change its temperature, state of matter or any other physical,
chemical and biological state.
• When two bodies at different temperature, thermal energy transfer
from the one with higher temperature to the one with low temperature.
Heat always transfers from hot to cold.
• Heat transfer is involved:
Sieving, mixing → heat transfer occurs (due to particle colloids/ collisions)
Tablets → Sieving – Mixing – Wetting – Drying – Sieving – Compression.
• it is typically given the symbol “Q” and is expressed in joules in SI units
the rate of heat transfer is measured in watts equals to joules per
Seconds denoted by “q”
• The heat flux, or the rate of heat transfer per unit area measured in
watts per area (W/m2
) and uses qn
for the symbol.
• Most common processes requiring heating are dissolving, melting,
evaporation, distribution, extraction, drying lyophilization and
sterilization.
• Temperature is non-additive physical property of material. Quantity of
heat Q is the quantity of energy absorbed or lost after thermal
interaction. The amount of heat Invested in to heating a body, in linear
proportion with mass off material (m) of specific heat (c).
Q = mc ∆t
• Heating can be performed directly or indirectly. Most common direct
heating is done with flame or other heating source. Example: Immersion
heaters, which means a heat transfer without any medium. Indirect heat
transfer with same medium.
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• Mixing of medium, which should be heated, assists more even and
consistent heat transfer in both cases. At heat transfer, magnitude of
transferred heat several phenomena can occur:
- Phase transition
- Polymorphism (property of material to exist in more than one
crystalline form)
- Pyrolysis
TYPES OF HEAT TRANSFER
1. Conduction
2. Convection
3. Radiation
1. CONDUCTION
• Conduction is the transfer of heat through materials by the direct
contact of matter. Dense metals like copper and aluminum are very
good thermal conductors. The ability to conduct heat often depends
more on the structure of a material than on the material itself.
THERMAL CONDUCTIVITY
• The thermal conductivity of a material describe how well the material
conducts heat.
FOURIER FORMULA FOR CONDUCTION
φ = 𝜆
A
L
∆T
• Where,
- φ = heat transfer
- λ = conduction factor
- A = surface area
- L = thickness
- ∆T = temperature difference
CONDUCTION RATE
• Conduction rate is expressed as:
Rate =
Driving force
Resistance
• The temperature difference is driving force and resistance to heat
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increases by greater thickness and decrease as co-efficient of thermal
conductivities increase and area becomes larger.
RELATIONSHIP B/W CONDUCTIVITY AND RESISTANCE
• Conductivity is inversely proportional to resistance.
k ∝
1
R
RESISTANCE OF COMPOUND LAYER
• The resistance of compound layer of material can be calculated as:
R ∝ L , R ∝
1
k
, R =
L
K
Total Resistence =
L1 + L2 + ⋯ Ln
K1 + K2 + ⋯ Kn
• The situation in a compound layer may be
represented in a convenient graphical form
using temperature and thickness as
ordinates, so that relative slopes of the
various sections of the temperature gradient
will be dependent upon the thermal
conductivity of the material of each layer as
shown in figure.
OVERALL COEFFICIENT OF HEAT TRANSFER
• To calculate heat transfer we have to know overall thermal conductivity
which can be obtained by reversing the process i.e. by taking reciprocal
of overall co-efficient of heat transfer "U" having unit w/m2
k and is
represented by:
U =
1
L1 + L2 + ⋯ 𝐿 𝑛/𝐾1 + K2 + ⋯ Kn
• To calculate heat transfer “U” is used instead of K/L, so that:
q = UA ∆T
2. CONVECTION
• Heat transfer by convection occurs due to movement of molecules and
their associated heat on a macroscopic level. It involves mixing of
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molecules and occurs within fluids where the molecules are free to
move.
HEAT TRANSFER BY NATURAL CONVECTION
• It occurs when there is a density difference within the fluid arising from
greater expansion and hence lower density of the fluid in hotter region.
HEAT TRANSFER BY FORCED CONVECTION
• It occurs when the fluid is forced to move e.g. by the movement of a
mixer blade or disruption caused by baffles.
• Heat transfer occurs more quickly by forced convection than by natural
convection owing to greater intensity of movement and therefore
increased velocity of fluid. Turbulence aids heat transfer.
HEAT CONVECTION EQUATION
• According to Newton's cooling law, specific formula for Convection heat
transfer
φ = αA ∆T
- α = Convection factor, A = area contacting fluids, ∆T =
temperature difference.
FACTORS AFFECTING HEATING OF FLUIDS
• Factors that affect heat transfer of fluids are as follows:
1. Steam
2. Air film
3. Condensate film
4. Scale
5. Metal wall
6. Liquid film
7. Liquid
DESIGN OF HEATING EQUIPMENT
• Following are parameters to be taken in designing heating equipment:
I. AREA
• Heating should take place over as large surface as possible.
II. TEMPERATURE
• A suitable temperature should be employed because it is directly
proportional to heat transfer.
III. MATERIAL OF CONSTRUCTION
• The plant should be made of suitable thermal conductivity material.
IV. GENERAL DESIGN
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• The design of plant should be such that it would minimize the resistance
due to surface layer.
V. AIR REMOVAL
• Elimination of air in steam is extremely important.
VI. CLEANLINESS
• The surface of vessel should be clean from deposits of solid.
VII. CONDENSATE REMOVAL
• The system should be arranged to allow correct drainage and removal of
the condensate from the steam.
VIII. LIQUID CIRCULATION
• Liquid movement should be arranged to ensure turbulent flow by
avoiding awkward shape. Stagnation might occur using for circulation if
natural circulation is inadequate due to density or viscosity changes.
3. RADIATION
• Radiation is heat transfer by electromagnetic waves. Thermal radiation is
electromagnetic waves including light produced by objects because of
their temperature. The higher the temperature of an object the more
thermal radiation it gives off.
• A hot body emits heat energy in the form of electromagnetic waves. If it
falls on another body some of the radiation may transmitted, some
reflects and a part is absorbed.
• The quality of emission is dependent on absolute temperature, total
energy, heat, wavelength and intensity.
BOLTZMAN FORMULA
φ = ϵσA𝑇
• Where,
- ε = emission capability, σ = radiation constant, T = absolute
temperature.
PHARMACEUTICAL APPLICATIONS OF HEAT TRANSFER
• Heat transfer is involved in many pharmaceutical processes:
- Melting
- Creating an elevated temperature during the production of
suppositories, creams and ointments.
- Controlled cooling of the same products.
- Heating of solvent to hasten dissolution process E.g. Dissolution of
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preservatives.
- Sterilization E.g. Autoclaves.
- Evaporation of liquids to concentrate the product.
- Heating or cooling of air in air conditioning plant.
- Drying of granules during tableting.
- Heating air to facilitate coating.
- Spray drying and freeze drying.
STEAM AS HEATING MEDIUM
• Steam is most commonly used in heating the pharmaceutical material to
affect drying and evaporation. In addition, it is most important in
sterilization.
REASONS FOR WIDE USE OF STEAM
• Steam has very high heat contents. Steam is given up at constant
temperature. The raw material water is cheap and plentiful.
• Steam is clean, odorless and tasteless so result of accidental
contamination is not serious.
• The alternative media oil could be very dangerous.
• Steam can be used as high pressure to generate electric power, at low
pressure it can be used for heating purpose.
HEAT IN VAPORS
• Vapors contain heat in 2 forms:
I. SENSIBLE HEAT
• Sensible Heat is that heat which can be detected by senses i.e.
temperature change is caused when heat is given up or given out.
II. LATENT HEAT
• Latent heat means invisible, which cannot be detected by change in
temperature. It is detected at constant temperature as a change of
phase occurs between solid and liquid or vapors.
PROPERTIES OF STEAM
• The properties can be discussed if one kg of water is taken in cylinder
enclosed in a friction less piston at constant temperature and pressure.
• When heat is added until the change occurs like water starts boiling, it
will take place at temperature (t) and amount of heat required is
sensible heat of water i.e. h = t – 0 KJ
• If more heat is added a fraction of water (q) will be vaporized.
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• If latent heat of vaporization is LKJ/kg then the amount of heat added is
qLKJ and total heat content is (steam water mixture) is h + qLKJ.
• Where q = dryness fraction of wet steam and can be expressed as
percentage or part of 1. Thus, steam may be expressed as 85% or 0.85
dry.
• If further heat is added a point will be reached when q = 1 i.e. all the
water has been evaporated and steam is dried, then total heat now
added is h + L = H x KJ at constant temperature.
PRACTICAL ASPECTS OF USES OF STEAM
• In practice, it is usual for steam to be generated centrally in the factory
and distributed in various items of process plant.
I. GENERATION OF STEAM
• High pressure to drive turbine for generating electric power. Low
pressure steam can be used for heating process. It is more economical.
II. DISTRIBUTION
• From boiler steam may be distributed through pipes which should be of
adequate size and length to avoid losses. The pipe should be (lagged)
cover with porous and poor conducting material like; asbestos or glass
wool. The best property of lagging is that it should be porous to trap a
stagnant layer of air as air is very poor conductor of heat. Sometimes
different layer of aluminum foil are used for insulation.
III. PRESSURE REDUCTION
• Generally, process plant uses steam at a pressure of 1.7-2 bars. So that a
reduction of pressure from boiler is necessary. This is done by reducing
valves. The pressure of spring attempts to open the valve against high
pressure steam. Closing of valve is caused by low pressure steam. A
balance will be reached in which low pressure steam acting on the
diaphragm closes the wall against the spring pressure.
• Expansion at the plant has advantage that some drying of steam can
place due to higher value of latent heat of vaporization at low pressure.
It is also known as throttling.
IV. USE OF STEAM IN PLANT
• It may be:
DIRECT
• In this case live steam is blown directly into the material; it has
advantage of direct efficiency and no boundary resistance to overcome.
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But the disadvantage is that condensate enters the material. It is useful
method of heating liquid if dilution is not important most specifically
used in steam distillation and sterilization.
INDIRECT
• In this case there is barrier between steam and material to be heated.
• This may be affected by means of jacket around the piece of plant or by
having a steam of coil or tubes through the vessels. The use of steam
jacket is convenient butt has the limitation, if vessel increases in size the
heating area decreases in volume.
V. CONDENSATE REMOVAL
• Indirect method of using steam in jackets or tubes must be enclosed
system to maintain the steam pressure and to prevent loss of steam.
This means condensate forms as steam gives up its latent heat, will
accumulate and water clog the system unless some arrangements are
made for condensate removal.
• Thus, a system must include a steam trap, a device to distinguish
between water and steam allowing former to discharge and later to be
retained. Steam traps may be divides into 2 classes:
MECHANICAL STEAM TRAPS
• It depends upon the critical difference between water and steam or
between vapor and liquid. It has advantage of possessing greater
strength and able to operate under variety of conditions than
thermostatic steam traps.
THERMOSTATIC STEAM TRAPS
• It depends upon that condensate can lose sensible heat and will be at
low temperature then steam. It is different from mechanical traps for
opening when the plant is not in use allowing condensate to drain and
air to sweep out from the system when starting up.
Moreover, mechanical traps are unable to distinguish between air and
steam.
VI. REMOVAL OF AIR
• It may be removed by use of thermostatic type of traps which will
operate when the proportional of air lower steam pressure sufficiently.
In addition, air vent can be used in same principle as in balance pressure
expansion trap.
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DRYING
DEFINITION
• ‘’A process in which the liquid is removed from a material by the
application of heat and is accomplished by the transfer of a liquid from a
surface into an unsaturated vapor phase’’
• This applies to the removal of small amount of water from moisture
bearing table salt as well as recovery of table salt from sea by
evaporation.
METHODS OF DRYING
• There are many non-thermal methods of drying:
1) Expression: of a solid to remove liquid.
2) Extraction: of liquid from a solid by use of solvent.
3) Adsorption: of water from a solvent by the use of desiccants.
4) Absorption: of moisture of gases by passing through sulfuric acid
(𝐻2 𝑆𝑂4)
5) Desiccation: of moisture from solids by placing it in a sealed
container with a moisture Removing material, (silica gel in a bottle)
THEORY
• It is an important process in almost all the pharmaceutical industries.
There is hardly any pharmaceutical plant engaged in the manufacture of
tablets or capsules, that does not use dryers.
• Drying is commonly last stage of the process before packing and has a
considerable effect on the properties of the product which may prevent
the deterioration, produce a readily soluble or free flowing product.
• Drying involves both heat and mass transfer operation. Heat must be
transferred to the material to be dried in order to supply the latent heat
required for vaporization of moisture. Mass transfer is involved in the
diffusion of water through the material to the evaporating surface, in
the subsequent evaporation of water from the surface and in the
diffusion of the resultant vapor into the passing air stream.
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• Drying involves:
- Heat transfer
- Mass transfer
HEAT TRANSFER
• Heat must be transferred to the material to be direct in order to supply
the latent heat required for the vaporization of the moisture, (phase
change). The rate of vaporization of the liquid film from the surface of
the material being dried depends upon:
dw
dQ(t)
=
q
λ
- Where, dw/dt = rate of evaporation, 1b of H2O/hr, q = overall
rate of heat transfer, λ = latent heat of vaporization of water.
• Heat transfer takes place by:
- Conduction
- Convection
- Radiation
• It means overall rate of heat transfer depends upon the sum of rate of
heat transfer by c, r, and k
S; q = qc + qr + qk
dw
dt
= qc + qr + qr/pi
- Where, qk, qc and qr are the rate of heat transfer by conduction,
convection and radiation, respectively.
MASS TRANSFER
• Mass transfer involves:
- Diffusion of water through the surface to the evaporation surface.
- The subsequent evaporation of water from the surface.
- The diffusion of resultant vapor into the passing air stream.
• Rate of diffusion of vapor into passing air stream depends on following
factors:
- Area of evaporating surface (A)
- Humidity difference (Hs-Hg)
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So,
dw
dt
∝ A (Hs − Hg)
dw
dt
= KA (Hs − Hg)
- Hs = absolute humidity of surface, Hg = absolute humidity of air
- Where, K = coefficient of mass transfer, is not a constant but
depends upon volume of air stream passing over the surface as:
k ∝ V 𝑛
k = C V 𝑛
- Where, V = volume, C = proportionality constant, n = fractional
exponent.
• After the start of drying there will be a production of initial adjustment.
After that, the rate of evaporation of liquid from the surface is equal to
the rate of diffusion of liquid from the body of solids. Which depends on
rate of heat transfer. So, the rate of heat transfer becomes equal to the
rate of mass transfer.
qc + qr + qk = KA (Hs − Hg)
Rate of diffusion
dw
dt
= K′A (Hs − Hg)
METHOD TO INCREASE RATE OF DRYING
• From the above equation we can increase the rate of by following ways:
- By increasing qC: the rate of convection heat transfer qC can be
increased by increasing the air flow rate and raising the air inlet
temperature.
- By increasing qr: the rate of radiation transfer can be speed up by
introducing the high temperature radiant heat source into the
drying chamber.
- By increasing qk: by reducing the thickness of material being dried
and by allowing it to come in contact with the raised temperature
surface.
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- By increasing K: increasing the air volume also speeds up the rate
of drying by increasing the coefficient of mass transfer K.
- By increasing (Hs-Hg): if inlet air is determined, humidity gradient
can be increased which is other mean of speeding up the rate of
drying.
GENERAL CLASSIFICATION OF THE DRYERS
CLASSIFICATION BASED ON METHOD OF SOLID HANDLING
I. STATIC BED DRYERS
• Tray & Truck Dryers
• Vacuum Shelf Dryers
• Tunnel Dryers
• Belt Dryers
• Drum Dryers
II. MOVING BED DRYERS
• Turbo Tray Dryers
• Rotary Dryers
• Vibratory Conveyor
Dryers
• Vacuum Tumble Dryers
• Pan Dryers
III. FLUIDIZED BED DRYERS
• Vertical Dryers • Horizontal Dryers
IV. PNEUMATIC DRYERS
• Spray Dryers • Flash Dryers
V. SPECIALIZED DRYERS
• Freeze Dryer
CLASSIFICATION BASED ON HEAT TRANSFER MODE
I. CONVECTION
• Flash Dryer
• Spray Dryer
• Fluid Bed Dryer
• Cabinet Dryer
• Tunnel Dryer
• Rotary Dryer
II. CONDUCTION
• Drum Dryer
• Agitated Pan Dryer
• Rotary Dryer
• Tray Dryer
III. RADIATION
• Infrared Shelf Dryer • Sun Dryer
IV. DIELECTRIC
• Microwave Oven
• Microwave Tunnel
• Radiofrequency Dryer
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V. COMBINED MODES
• Microwave Convective Dryer
• Infrared Convective Dryer
1. STATIC BED SYSTEM
I. TRAY AND TRUCK OR SHELF DRYERS
• They are also known as cabinet or compartment dryers. There are
usually hot air ovens.
PRINCIPLE
• In these types of dryers there is no static relative movement among the
solid particles being dried. Only a fraction of a total number of particles
is directly exposed to the heat sources.
• The exposed surface can be increased by decreasing the thickness of the
bed.
DESIGN AND WORKING
TRAY DRYERS
• Tray dryers consist of a cabinet in which the material to be dried is
spread on trays. The number of trays varies with the size of dryer.
• Dryers of laboratory size may contain as few as three trays.
TRUCK DRYER
• Truck dryer is one in which the trays are located in trucks which can be
rolled into and out of the drying cabinet in pharmaceutical industries.
Truck dryers are preferred over tray dryers because of convenience in
loading and unloading the drying cabinets.
TYPES OF TRAY DRYERS
DIRECT DRYER
• Most tray dryer used in pharmaceutical industry are direct dryers, in
which heating is accomplished by the forced circulation of large volume
of heated air.
INDIRECT DRYER
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• They utilize heated shelves inside the drying chamber to evaporate the
moisture which is then removed by vacuum pump. The preferred
energy source for heating the drying air used on pharmaceutical
products are steam or electricity. Steam is preferred over electricity
because steam energy is cheaper.
ADVANTAGES
• Drying by tray dryer is a batch process rather than continuous drying in
industry, batch drying is preferred because each batch can be dried
separately.
• Same equipment can be used for drying a wide variety of materials.
• Used for damp solid material drying.
DISADVANTAGES
• Only few particles are exposed to heat.
• Electricity cost is high.
II. TUNNEL DRYER
• It is a modification of tray dryer in which oven Is replaced by a long
tunnel.
OPERATION
• The material to be dried is entered at one end and the dried material is
collected at the other end of the tunnel. The trays containing the wet
material is loaded on trucks which have an automatic speed control.
• In the multiple belt conveyer system, the partially dried material which
has completed one side moves automatically from the end of 1st
conveyer on to the 2nd
conveyer moving in opposite direction. In this
way the product may successfully travel five times along the tunnel
before its discharged at the other end of the tunnel.
ADVANTAGES AS COMPARED TO TRAY DRYERS
• It is semi continuous in operation and can be used for the large-scale
production.
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2. MOVING BED SYSTEM
I. TURBO TRAY DRYERS
PRINCIPLE
• Drying particles are partially separated so that they flow over each
other. Motion may be induced either by gravity or mechanical agitation.
DESIGN AND WORKING
• Turbo dryer consist of a series of rotating angular
trays arranged in vertical stack. Heated air is
circulated over the trays by turbo-type fans. Wet
mass fed through the roof of the dryer and is leveled
by a stationary wiper. After about 7-8 of the
revolution the material being dried onto the tray
below where it is again spread and leveled. The
same procedure is continued throughout the height
of the dryer until the dried material is discharged at
the bottom.
ADVANTAGES
• Because turbo dryers continuously expose new surfaces to air, drying
rates are considerably faster than tray dryers.
DISADVANTAGES
• Expensive, Complicated.
II. ROTARY DRYERS
• The rotary dryer is modified form of tunnel dryer in which particles are
passed through a rotating cylinder, counter current to stream of heated
air. Due to the rotation of cylinder, the material is turned over and
drying takes place from individual particles and not from a static bed.
• The cylindrical shell is mounted with a slight slope so as to discharge the
material and make the operation continuous. Baffles or flights in the
shell may increase the rate of drying.
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3. FLUIDIZED-BED SYSTEMS
• If a gas is allowed to flow upward through a bed of particulate solids at a
velocity greater than the settling velocity of the particles and less than
the velocity for pneumatic conveying, the solids are buoyed up and
become partially suspended in the gas stream.
• The resultant mixture of solids and gas behaves like a liquid, and the
solids are said to be fluidized.
• This is used for the granular solids because each particle is surrounded
by the drying gas.
PRINCIPLE
• Solid particles are partially suspended in an upward moving gas stream.
The particles are lifted and then fall back in a random manner, so that
the resultant, mixture of solid and gas acts like a boiling liquid and the
solid are said to be fluidized.
• This technique is very useful and efficient and it is used for drying
granular solids because each particle is surrounded by the drying gas.
TYPES OF FLUIDISED BED DRYERS
VERTICAL
• Used for batch drying.
HORIZONTAL
• Used for continuous drying.
DESIGN
• It consist of stainless-steel chamber
with a perforated bottom into which
the wet material to be dried is placed.
For loading and unloading, the drying
chamber is removed from the unit.
The air is introduced from below
which is heated by means of heaters
fitted there in and it is then passed
through the powder by means of fan
fitted in the upper part of the
apparatus.
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23. GM Hamad
REQUIREMENT
• The requirement is that:
- Granules are not so wet that they stick together on drying.
WORKING
• The air is heated to the required temperature and its flow rate is
adjusted as the velocity of air is increased, the bed begins to expand.
• Further increase in velocity beyond this point will cause rapid expansion
of the bed and particles will begin to show turbulent motion.
FLUIDISATION
• The particles are not in direct contact with each other and efficient heat
exchange take place between the particles and the following air. The
moist air is carried away rapidly.
PURPOSE
• The purpose of this SOP is to describe the procedure to be followed
while operating the Fluid Bed Dryer to achieve the following objectives:
- To fulfill the GMP requirement.
- For personnel and machine safety.
- For efficient operation.
- To ensure proper washing and cleaning of equipment to produce
quality products.
SCOPE
• This SOP is valid for the Production department of SRP Plant.
PERSONNEL
• Wear mask, gloves and specified gown during all operations.
PRECAUTIONS
• During drying if lumps are observed, switch off the dryer. Take out the
trolley and paddle the product container, so to break the lumps and
level the product bed in the trolley.
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24. GM Hamad
• Observe that granules should not be over fluidized so as to avoid
attrition of granules.
STARTING
• Connect the air and electric supply.
• Load the Fluid Bed Dryer Bowl with product.
• The quantity should be appropriate for good fluidization.
• Introduce trolley into the space meant for it properly.
• Assure that bowl is well fitted in its space in the dryer.
RUNNING
• Adjust the drying temperature.
• Check that the product is completely fluidized then reduce the air flap
level until fluidization is just maintained.
• Observe that the granules are in fluidized state.
• If needed, press the shake device so as to maintain fluidization.
• Close the air flap and switch off the dryer, press shake device so if any
product that is remained in the filter should slide down into the trolley.
• Take out the trolley and observe the granules.
• Transfer the dried granules or material from Fluid Bed Dryer trolley into
polyethylene lined labeled drums.
ENDING (CLEANING)
• After completion of drying process, remove the trolley from dryer.
• Collect the dried granules in polyethylene lined labeled drums by means
of scoop.
• Clean and wash the trolley with hot water.
• Clean thoroughly inner and outer side of dryer with clean duster.
• In case of product change over, remove the filter ring and clean it.
• Wash the top and bottom of dryer thoroughly with hot water to remove
the traces of previous product.
• Also wash the trolley with hot water.
• Finally rinse with purified water.
ADVANTAGES
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25. GM Hamad
• They are efficient as 5-200kg material can be dried within 20-40 mins
compared with 24 hours in tray dryers
• Drying takes place from individual particles and not from whole bed
• The temperature of fluidized bed dryer can be controlled
• A free-flowing product is produced
• Due to short drying time unit has high output
• No caking or agglomeration
• Drying from all sides and not only surface.
DISADVANTAGES
• Complicated
• Skilled persons are required
• Too wet granules stick together
• Overheating causes brittle granules and tablet defects occur.
• Many organic powders develop electrostatic charges during fluidization
so efficient electrical earthing is necessary.
4. PNEUMATIC BED SYSTEM
SPRAY DRYERS
• They are used for drying only liquid materials such as solution, slurries,
pastes and suspensions.
PRINCIPLE
• In this method, the liquid is dispersed as fine droplets into a moving
stream of hot air, where they are evaporated rapidly before reaching the
wall of chamber. The product dries into a fine powder which is collected
into a collection system.
DESIGN
• All spray dryers consist of following components:
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26. GM Hamad
- Feed delivery system
- Drying chamber
- Solid gas separator
- Atomizer
- Heated air supply
- Product collector
- Cyclone
WORKING
• The liquid to be dried is fed to atomizer by use of suitable pump. The
rate of feed adjusted in such a way that each droplet of sprayed liquid is
completely dried before reaching the walls of drying chamber and yet
the dried powder is not overheated in the process.
• The inlet air temperature is kept constant. Too high temperature can
result in improper drying. Similarly, excessive feed rates will lower the
outer temperature due to which the material will be collected on the
walls of the chamber.
• The disc of atomizer D is driven by an air turbine and spins at 35000 rpm.
Air is introduced with help of fan which is heated by means of electric
heaters to a maximum temperature of 350℃. The spray droplets from
atomizer come in contact with the hot air.
• The droplets rapidly evaporate in the drying chamber. The dried powder
is separated from the gas in cyclone separator and collected in
container.
ADVANTAGES
• Liquid material can be dried
• Drying is very rapid and fast
• Thermostable substances can easily be dried
• Sterile solution can be dried
• The dried powder will have uniform particle size and shape
• Powder formed has good flow properties
• Labor cost are low
• Material up to 200 kg per hour can be handled.
DISADVANTAGES
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27. GM Hamad
• The equipment is very bulky and costly
• There is a lot of wastage of heat.
5. SPECIALIZED DRYERS
FREEZE DRYING
• It is process by which water is removed from the liquid product after it is
frozen by sublimation. Hence this is also known as FREEZE DRYING or
SUBLIMATION.
PRINCIPLE
• Liquid is first frozen to ice before application of vacuum to avoid
frothing, then sublimation of frozen ice is carried out under reduced
pressure.
• The vaporization of ice occurs only at the surface; hence the frozen ice is
exposed to large surface area.
PROCEDURE
• Freeze drying on large scale may be carried out by freezing the product
in a container kept on the shelf of a chamber by circulating a refrigerant
like ammonia or ethylene glycol from the compressor through the pipes
fitted along the series of shelf.
• When freezing is complete; vacuum is applied to the chamber which has
been previously chilled by means of circulating the refrigerant from
large compressor.
• Heat is then supplied to the product by heating coils. The process is
continued till the product is dry and a spongy solid material is left
behind which is collected in container.
APPLICATIONS
• For the manufacturing of certain pharmaceuticals or biological products
which are thermolabile.
• For drying blood plasma, vitamins, hormones, enzymes and antibiotics,
thus preserving these for years.
• Freeze dried products have definite physical properties as compared to
other products derived by other methods.
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28. GM Hamad
• Freeze dried products are more stable and are readily soluble.
DISADVANTAGES
• Slow process
• Very costly
6. VACUUM DRYERS
• Also known as vacuum oven. It consists of jacketed vessel. It has to
withstand vacuum in the oven and steam present in the jacket.
• Oven and dryer can be loaded with air-tight seal. It is connected to a
vacuum pump through a condenser and receiver.
• At a vacuum of 0.03 to 0.06 bar water boils at 350℃.
ADVANTAGES
• Very suitable for heat sensitive products
• Porous and friable product is obtained
• Valuable solvents can be recovered
DISADVANTAGES
• Heat transfer may be low and non-uniform
• Limited capacity
• Labor and running costs are high
• Finely divided powder may be drawn into the vacuum pump.
APPLICATIONS OF DRYING
• Drying is an important process which is used by almost all the
pharmaceutical industries.
• Drying has following applications in pharmacy:
1. For the preparation of granules which can be dispensed in bulk,
compressed in the form of tablets or filled in capsules.
2. For the preparation of certain products like dried aluminum
hydroxide, dried lactose cad powdered extracts.
3. For reducing the bulk and weight of powder and thus reducing the
cost of transportation and storage.
4. Vegetable drugs are dried before extraction to facilitate grinding
and to avoid deterioration on storage.
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29. GM Hamad
5. As dried products are more stable than moist ones so stable
products are produced by drying.
6. Drying has the considerable effects on the properties of product
and it produces a readily soluble and free flowing products.
7. Thermolabile substances can be dried using spray dryer.
DRYING OF SOLIDS
1. LOSS ON DRYING
The moisture in a solid can be expressed on a wet weight or dry weight
basis. On wet weight basis, the water content of a material and is calculated
as a percentage of weight of the wet solid. whereas on the dry weight basis,
the water is expressed as a percentage of weight of the dry solid. The term
loss on drying is an expression of moisture content on a wet weight basis,
calculated as:
%LOD =
Weight of water in sample
Weight of wet sample
⨯ 100
2. MOISTURE BALANCE
• The LOD of a wet solid is often determined by the use of moisture
balance, which has a heat source of rapid heating and a scale calibrated
in percent LOD.
• A weigh sample is placed on a balance and is allowed to dry until a
constant weight is achieved. The water lost by evaporation is read
directly from the percent LOD scale. It is assumed that there are no
other volatile materials present.
3. MOISTURE CONTENT
• Another measurement of the moisture in a wet solid is that calculated
on a dry weight basis. This value is referred to as moisture content or
MC, calculated by:
%MC =
Weight of water in sample
Weight of dry sample
⨯ 100
• LOD value can vary in any solid fluid mixture from slightly above 0 to
above 100%. But the MC value can change from slightly above 0 and
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30. GM Hamad
approach infinity. Thus, percent MC is a far more realistic value than
LOD, in the determination of dryer and capacity.
BEHAVIOR OF SOLIDS DURING DRYING
• It helps in determine:
- Time required to dry a certain batch in given dryer
- Size of dryer required for certain drying process.
• It is done by using a cabinet with a weighing scale provided that
conditions are of a large dryer and are properly simulated. The
information's obtained in drying in such an environment can be plotted
on a graph between moisture contents and drying rate.
1. INITIAL ADJUSTMENT
• When a wet solid is first placed in an oven, it undergoes initial
adjustment to the environment. During the production, it absorbs heat
and at the same time losses some moisture. Drying rate begins to
increase.
2. CONSTANT RATE PERIOD
• Temperature remains constant, moisture evaporating from solid surface
is replaced by more moisture which diffuses through capillary force, as a
result drying rate remains constant.
3. FIRST FALLING RATE PERIOD
• At this point, the speed at which moisture evaporates from the surface
exceeds the speed at which moisture diffuses to surface from the
bottom. Hence, a continuous drying cannot be maintained. As a result,
dry spots are formed. The moisture content at which this occurs is
termed as “Critical Moisture Content” With the passage of time, the no.
of dry spots keeps on increasing. Hence, during this stage, rate falls
steadily. This period is also termed as unsaturated surface drying.
4. SECOND FALLING RATE PERIOD
• The whole solid surface dries out and the rate of drying depends upon
diffusion of the moisture to the surface which is very low. Therefore,
rate of drying falls even more sharply than in the previous period. Point
D is referred to as 'second critical point’
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31. GM Hamad
5. EQUILIBRIUM MOISTURE CONTENT
• Drying rate = 0, then an equilibrium is attained between moisture
content in the solid and in the air. There cannot be any further loss of
moisture and any further heating will be useless.
GRAPH BETWEEN MOISTURE CONTENTS AND DRYING RATE
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32. GM Hamad
COMMINUTION (SIZE REDUCTION)
MILLING
• “Milling is the mechanical process of reducing the particle size of solids.”
• Various terms (commination, crushing, disintegration, dispersion,
grinding, and pulverization) have been used synonymously with milling
depending on the product, equipment and the process.
• Milling equipment is usually classified as coarse, intermediate or fine
according to the size of the milled product.
WHY MILLING? / IMPORTANCE OF MILLING
• Milling or grinding offers a method by which these particles can be
produced.
• The surface area per unit weight, which is known as the specific surface,
is increased by size reduction. In general, a 10-fold increase in surface
area has been given by a 10-fold decrease in particle size. This increased
surface area affects:
I. DISSOLUTION AND THERAPEUTIC EFFICACY
• Dissolution and therapeutic efficiency of medicinal compounds that
possess low solubility in body fluids are increased due to increase in the
area of contact between the solid and the dissolving fluid.
EXAMPLES
• The control of fineness of griseofulvin led to an oral dosage regimen half
that of the originally marketed product.
• In inhalational products, the size of particles determines their position
and retention in the bronchopulmonary system.
• Transdermal delivery is also facilitated by particle size reduction.
II. EXTRACTION
• Extraction or leaching from animal glands (liver and pancreas) and crude
vegetable drugs is facilitated by communition. The control of particle
size in the extraction process provides for more complete extraction and
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33. GM Hamad
a rapid filtration rate when the solution is filtered through the mare.
III. DRYING
• The drying of wet masses may be facilitated by milling, which increases
the surface area and reduces the distance that the moisture must travel
within the particle to reach the outer surface. Micronization and
subsequent drying also increases the stability because the occluded
solvent is removed.
EXAMPLE
• In the manufacture of compressed tablets by wet granulation process,
the sieving of the wet mass is done to ensure more rapid and uniform
drying.
IV. FLOWABILITY
• The flow property of powders and granules is affected by particle size
and size distribution. The freely flowing powders and granules in high-
speed filling equipment and tablet presses produce a uniform product.
For suspensions of high disperse phase concentration, reduction in
particle size leads to increase in viscosity.
V. MIXING OR BLENDING
• The mixing or blending of several solid ingredients of a pharmaceutical is
easier and more uniform if the ingredients are of approximately the
same size. This provides a greater uniformity of dose.
• Solid pharmaceuticals that are artificially colored are often milled to
distribute the coloring agent to ensure that the mixture is not mottled
and uniform from batch-to-batch. Even the size of a pigment affects its
color.
VI. FORMULATION
• Lubricants used in compressed tablets and capsules function by virtue of
their ability to coat the surface of the granulation or powder. A fine
particle size is essential if the lubricant is to function properly.
VII. RATE OF ABSORPTION
• Smaller the particle size quicker and greater will be the rate of
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34. GM Hamad
absorption. For example: rectal absorption of aspirin from a theobroma
oil suppository is also related to particle size.
VIII. EMULSION STABILITY
• Stability of emulsions is increased by decreasing the size of oil globules.
E.g. microemulsions are more stable.
IX. FILLING EQUIPMENT
• The flowability of powders, granules in high speed filling equipment and
in tablets presses is dependent upon size of particles.
X. LUBRICANTS
• A fine particle size is necessary if a lubricant is to function properly in
compressed tablets or capsules.
DISADVANTAGES OF SIZE REDUCTION
• Loss of aromatic and volatile ingredients: On grinding aromatic and
volatile content of crude drugs maybe lost ducts elevated temperature.
• Increased oxidation and reduction: Increased surface area due to size
reduction when exposed to atmospheric conditions may result in
oxidation and hydrolysis of the product.
• Caking in suspension due to small particles.
• Decrease in flow ability due to decrease in particle size.
• Very fine particles are not favorable for tablet preparation.
• Surface gets charged and particles aggregate.
• Some drugs degrade on milling.
• Some drugs melts upon milling due to increased temperature during
milling.
• Polymorphism occurs and crystal’s habit is changed.
FACTORS INFLUENCING MILLING
I. HARDNESS
• It is the surface property of the materials in general; harder the material
difficult is to reduce the size. However, if the material is very hard and
brittle also the size reduction may present no special problem.
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35. GM Hamad
II. TOUGHNESS
• A soft but tough material may present more problems in size reduction
then hard and brittle substances. E.g. a blackboard chalk can be broken
more easily than a rubber. Toughness can be reduced by treating the
material with liquefied gas such as nitrogen.
III. ABRASIVENESS
• It is the property of hard materials. During grinding of some very
abrasive substances, the final powder may become contaminated with
more than 0.1% of metal worn from grinding mill.
IV. STICKINESS
• It may cause considerable difficulty in size reduction as materials may
adhere to grinding surfaces or the meshes of screen may become
choked. Complete dryness helps milling. Addition of inert substances
could be assistance e.g. addition of kaolin to sulfur and DDT has been
advantageous.
V. SOFTENING TEMPERATURE
• Heat generated during milling can cause some substances to melt thus
causing problems. E.g. gummy or resinous substances.
VI. MATERIAL STRUCTURE
• Material structure may have lines or weakness along which the material
splits to form flake like particles.
VII. MOISTURE CONTENT
• In general, materials should be dry or wet; not merely damp. For dry
grinding less than 5% moisture is suitable when for wet grinding more
than 50% moisture is suitable.
VIII. PHYSIOLOGICAL EFFECT
• For potent drugs e.g. podophyllum, hormones, small amount of dust
may affect the operators, thus and enclosed mill should be used.
IX. PURITY REQUIRED
• When high degree of purity of product is designed, apparatus causing
wear off the grinding surface should be avoided.
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36. GM Hamad
X. SIZE OF FEED MATERIAL
• For very fine product it may be necessary to carry out the size reduction
in several stages depending upon the size of feed material. E.g.
preliminary crushing followed by coarse grinding and then fine grinding.
XI. BULK DENSITY
• The capacities of most batch mills depend on volume, thus the output of
machine is related to bulk density of the substances.
PARTICLE SIZE DISTRIBUTION (PSD)
• The particle-size distribution (PSD) of a powder, or granular material, or
particles dispersed in fluid, is a list of values or a mathematical function
that defines the relative amount, typically by mass, of particles present
according to size.
• It has a specific range i.e. between 1-100um. Average is always taken out
by mean and median.
EXAMPLE
• For a powder if we take reference of 10um then D10 = 10% particles are
of 10um and remaining 90% are greater than 10um (coarse powder)
• D50 = 50% particles are of 10um and remaining 50% are greater than
10um (fine powder)
• D90 = 90% particles are of 10um and remaining 10% are greater than
10um (very-fine powder)
SIZE ANALYSIS
• Particle size analysis, particle size measurement, or simply particle sizing
is the collective name of the technical procedures, or laboratory
techniques which determines the size range, and/or the average, or
mean size of the particles/ particle size distribution in a powder or liquid
sample.
SIEVING
• Sieving is the most widely used method for measuring particle size
distribution because it is inexpensive, simple, and rapid with little
variation between operators. Although the lower limit of application is
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37. GM Hamad
generally considered to be 50 microns, micromesh sieves are available
for extending the lower limit to 10 microns.
• A sieve consists of a pan with a bottom of wire cloth with square
openings. The procedure involves the mechanical shaking of a sample
through a series of successively smaller sieves and the weighing of the
portion of the sample retained on each sieve. The type of motion
influences sieving: vibratory motion is most efficient, followed
successively by side-tap motion, bottom-tap motion, rotary motion with
tap, and rotary motion.
• The B.P. specifies five grades of powder are:
Grade of powder Sieve through which all particle must pass
Coarse 10
Moderately coarse 22
Moderately fine 44
Fine 85
Very fine 120
NUMBER OF SIEVES
• This is the number of meshes in a length of 25.4 mm (1in) in each
direction parallel to the wires.
OTHER METHODS
• Sedimentation Methods
• Elutriation Techniques
• Microscopic Sizing and Image Analysis
• Electrical Impedance Method
• Laser Diffraction Methods
THEORY OF COMMINUTION
STRESS-STRAIN CURVE
• Compression at any point along the line below the yield value, the
material
will go back and returns to its original shape and this is called elastic
deformation. However, compression above the yield value will result in
plastic deformation in which the substance break down and not go back
to its original shape after removing stress.
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38. GM Hamad
GRIFFITH THEORY
• The Griffith theory of cracks and flaws assumes that all solids contain
flaws and microscopic cracks, which increase the applied force according
to the crack length and focus the stress at the atomic bond of the crack
apex.
• The Griffith theory may be expressed as:
T = √
Yϵ
c
• Where, T is the tensile stress, Y is the Young's modulus, 𝜖 is the surface
energy of the wall of the crack and c is the critical crack depth required
for fracture
ENERGY OF COMMINUTION
• The energy required to reduce the size of particles is inversely
proportional to the size raised to some power. This general differential
equation may be expressed mathematically as:
dE
dD
= −
C
Dn
• Where, dE is the amount of energy required to produce a change in size,
dD, of unit mass of material, and C and n are constants.
KICK'S LAW
• In 1885, Kick suggested that the energy requirement, E, for size
reduction is directly related to the reduction ratio (D1/D2). Kick's theory
may be expressed as:
E = Cln
D1
D2
• Where, D1 and D2 are the diameters of the feed material and discharged
product, respectively. The constant C may be regarded as the reciprocal
efficiency coefficient.
• Kick's equation assumes that the material has flaws distributed
throughout its internal structure that are independent of the particle
volume.
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39. GM Hamad
RITTINGER'S LAW
• In 1867, von Rittinger proposed that the energy required for size
reduction is directly proportional to the increase in specific area surface
as expressed by the following relationship:
𝐸 = 𝑘1(𝑆2 − 𝑆1)
• Where, k1 denotes the relationship between the particle surface and
diameter, and S1 and S2 are the specific surface before and after milling,
respectively.
• In terms of particle diameters:
E = C′
[
1
D2
−
1
D1
]
• It is most applicable to brittle materials. Rittinger’s theory ignores
particle deformation before fracture although work is the product of
force and distance.
BOND'S LAW
• In 1952, Bond suggested that the energy required for size reduction is
inversely proportional to the square root of the diameter of the product.
This may be expressed mathematically as:
Wtα 1/√D2
• Where, Wt is the total work of comminution in kilowatt hours per short
ton of milled material, and D2 is the size in micrometers through which
80% by weight of the milled product will pass.
MILLING RATE
• The mass and size of particles and the time in the mill affect the milling
rate. It has been reported that batch milling of brittle materials in small
mills follows the first-order law. The original particles are fractured to
produce first-generation particles, which are then fractured to produce
second-generation particles, which are also fractured, and so on.
MECHANISM OR COMMINUTION
• Mills are equipment designed to impart energy to the material and
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40. GM Hamad
cause its size reduction. There are four main methods of effecting size
reduction, involving different mechanisms:
I. CUTTING
• It involves application of force over a very narrow area of material using
a sharp edge of a cutting device.
II. COMPRESSION
• In compression, the material is gripped between the two surfaces and
crushed by application of pressure.
III. IMPACT
• It involves the contact of material with a fast-moving part which imparts
some of its kinetic energy to the material. This causes creation of
internal stresses in the particle, there by breaking it.
IV. ATTRITION
• In attrition, the material is subjected to pressure as in compression, but
the surfaces are moving relative to each other, resulting in shear forces
which break the particles.
EQUIPMENTS
• A mill consists of three basic parts:
- Feed chute, which delivers the material
- Grinding mechanism, usually consisting of a rotor and stator
- A discharge chute.
• The principle of operation depends on cutting, compression, impact
from a sharp blow, and attrition. In most mills, the grinding effect is a
combination of these actions.
OPEN-CIRCUIT MILLING
• If the milling operation is carried out so that the material is reduced, to
the desired size by passing it once through the mill, the process is known
as open-circuit milling.
CLOSED-CIRCUIT MILL
• A closed-circuit mill is the one in which the discharge from the milling
chamber is passed through a size-separation device or classifier and the
oversize particles are returned to the grinding chamber for further
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41. GM Hamad
reduction of size. Closed-circuit operation is most valuable in reduction
to fine and ultra-fine size.
CLASSIFICATION TREE OF MILLS
1. CUTTER MILL
PRINCIPLE
• The basic principle of cutter mill is Cutting and shearing.
CONSTRUCTION
• The rotary knife cutter has a horizontal rotor with 2
to 12 knives spaced uniformly on its periphery turning
from 200 to 900 rpm and a cylindrical casing having
several stationary knives. The bottom of the casing
holds a screen that controls the size of the material
discharged from the milling zone.
• A disc mill consists of two vertical discs, each may be
rotating in the opposite directions (double-runner
disc mill), or only one may be rotating (single-runner
disc mill), with an adjustable clearance. The disc may be provided with
cutting faces, teeth, or convolutions. The material is pre-milled to
approximately 40-mesh size and is usually suspended in a stream of air
or liquid when fed to the mil.
• Cutting mills are used for tough, fibrous materials and provide a
successive cutting or shearing action rather than attrition or impact.
Mills
Cutting
Cutter
Compression
Roller
Colloid
Edge and end
runner
Impact
Hammer
Attrition
Pin
Ball
Vibro-energy
Fluid energy
Spiral jet
Homogenization
Simple
Silver son
Ultrasonic
High pressure
Microfluidizer
Low-pressure cyclone
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42. GM Hamad
WORKING
• Feeding of particle in the mill through the hopper. Milling is done
through the movement of rotating knives against stationary knives. Size
reduction occurs by fracture of particles between two sets of knives. The
screen retains the particles until a sufficient degree of size reduction
occurs.
OPERATION
• The feed size should be less than 1 inch in thickness and should not
exceed the length of the cutting knife. For sizes less than 20-mesh, a
pneumatic product-collecting system is required. Under the best
operating conditions, the size limit of a rotary cutter is 80-mesh.
USES
• Used to obtain a coarse degree of size reduction of soft materials such as
roots and peels before its extraction.
• Cutter mill is used for size reduction of tough & fibrous material like
animal tissues, medicinal plants, and plant parts. It is also used in the
manufacture of rubber, plastics and plastic material.
LIMITATIONS
• Not used for friable materials.
• The fed size should be less than 1 inch thick & should not exceed the
length of the cutting knife.
• The material is pre-milled and is usually suspended in a stream of air or
liquid when fed to the mill.
2. ROLLER MILLS
PRINCIPLE
• Roller mills consist of two to five smooth rollers operating at different
speeds. Thus, size reduction is effected by a combination of compression
and shearing action.
CONSTRUCTION AND WORKING
It consists of one or more rollers and is commonly used. Of these, the three-
roller types are preferred. In operation, rollers composed of a hard, abrasion-
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43. GM Hamad
resistant material, and arranged to come into close
proximity to each other are rotated at different rates.
Depending on the gap, the material that comes
between the rollers is crushed, and also sheared by the
difference in rates of movement of the two surfaces.
USES
• For crushing seeds before extraction of fixed oil
• Used to crush soft tissue to help in penetration of solvents.
VARIANTS
• Multiple smooth rollers or corrugated, ribbed, or saw-toothed rollers
can provide cutting action also
3. COLLOID MILL
PRINCIPLE
• The basic principle of colloid mill is compression and shearing.
CONSTRUCTION
I. ROTOR AND STATOR
• A high-speed rotor, fixed to the housing with a
shaft. Rotor moves at the speed of 3000-20,000
rpm. Rotor is with conical milling surfaces. Just
under the rotor, there is stator.
• Rotors and stators may be either smooth-
surfaced, or rough-surfaced. With smooth-
surfaced rotors and stators, there is a thin,
uniform film of material between them which is
subjected to maximum amount of shear. Rough-surfaced mills add
intense eddy currents, turbulence, and impaction to the shearing action.
Rough-surfaced mills are useful with fibrous materials because fibers
tend to interlock and clog smooth-surfaced mills.
II. MOTOR
• It rotates the rotor.
III. ADJUSTABLE CLEARANCE
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44. GM Hamad
• The gap between rotor and stator is fitted with adjustable clearance that
can be adjusted from 0.002-0.03 inches.
IV. HOPPER
• Just above the rotor, is a hopper for material input.
V. OUTLET
• In the periphery of housing, is an outlet for discharge of material.
WORKING
• It works on the principle of shearing consisting of conical rotor and
stator. A colloid mill consists of a high-speed rotor (3,000 to 20,000 rpm)
and a stator with conical milling surfaces between which an adjustable
clearance ranging from 0.002 to 0.03 inches is present.
• The material to be grounded should be pre-milled as finely as possible to
prevent damage to the colloid mill. The reduced material is then fed into
the machine through a hopper which is thrown outward by centrifugal
action. As the material pass through a narrow gap between rotor and
stator its size is reduced.
USES
• These are used primarily for the comminution for solids and dispersion
of suspensions containing wetted solids and preparations of viscous
emulsions.
ADVANTAGES
• Products with particle size less than 1um can be obtained.
• Useful for preparing pharmaceutical syrup, emulsions, lotions, ointments
and creams.
• Size reduction is always carried out in the presence of liquid.
DISADVANTAGES
• Not applicable for processing dry materials.
• Materials need to be milled previously.
• Suspensions may be aerated due to colloid mill.
4. EDGE-AND END-RUNNER MILL
EDGE RUNNER MILL
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45. GM Hamad
OTHER NAMES
• Chaser mill
PRINCIPLE
• It is basically a mechanical pestle and mortar for large scale production.
The basic principle of Edge-runner Mill is compression due to the weight
of the pestle and shear.
CONSTRUCTION
• It consists of the following parts:
- Rollers
- Shafts
- Bed or base
- Adjustable clearance
• The edge-runner mill consists of one or two heavy
granite or cast-iron wheels or mailers mounted on a horizontal shaft and
standing in a heavy pan.
I. ROLLERS
• Two heavy, steel or granite wheels revolve or chase each other on a
steel or granite the base giving the name chaser mill. The stone may be
as heavy as six tons and having a diameter of 0.5 to 2.5m.
• The large size roller may weigh up to 6 tons.
II. SHAFTS
• The rollers are mounted on a horizontal shaft and turns around a vertical
shaft.
III. BED OR BASE
• Made up of steel or granite. Usually the wheels are rotated but
sometimes the base is made to rotate.
IV. ADJUSTABLE CLEARANCE
• The height between the rollers and the base determines the particle size
of the material hence the fineness of the particles can be increased or
decreased by adjusting the height.
WORKING
• The material is fed into the center of the pan and is worked outward by
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46. GM Hamad
the mulling action. Milling occurs by compression, due to the weight of
the muller, and by shearing.
• Both mills operate at slow speeds on a packed bed. Both produce
moderately fine powders and operate successfully with fibrous
materials. Wet grinding with very viscous materials such as ointments,
pastes are also possible.
USES
• Edge runner mill is used for grinding tough materials to fine powder. It is
still used for plant-based products.
ADVANTAGES
• Simple to operate, require less attrition.
• Easy maintenance
• No problem of jamming
• Used to reduce size of extremely tough and fibrous roots and barks.
DISADVANTAGES
• Require more floor space than other commercial machines
• Output is less
• Cannot accommodate wet grinding.
END RUNNER MILL
• End runner mill is used for grinding tough materials to fine powder. It is
suitable for fine grinding.
PRINCIPLE
• It works on the principle of crushing and shearing.
CONSTRUCTION
• The end-runner mill is similar in principle and
consists of a rotating pan or mortar made of cast
iron or porcelain. A heavy pestle is mounted
vertically within the pan in an off-center position.
• It consists of following parts:
I. MORTAR
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47. GM Hamad
• A moveable mortar made up of steel or granite.
II. PESTLE
• Made up of same material as that of mortar. It is dumble shaped and
heavy. It is mounted eccentrically in mortar through a hinged joint.
Pestle is free to rise and fall in mortar.
III. MOTOR
• It is needed to rotate the mortar.
IV. SCRAPPER
• Scrapper is attached to the mortar which constantly removes the
material from the pestle and thus returning them back to the mortar.
WORKING
• The material to be ground is put in the mortar, which is rotated
mechanically. The pestle rotates itself by friction. The material is crushed
and rubbed between the pestle and the rotating mortar. The scrapper
removes the sticking material from the pestle and returns back to the
mortar for grinding. The ground material is passed through the sieve to
get the powder of required size.
PHARMACEUTICAL APPLICATIONS
• They are used for reduction of tough and fibrous materials.
• Used also for coarse materials.
• Used for the reduction of roots and barks to form the powder.
ADVANTAGES
• Suitable for reducing particle size of coarse materials.
• Completely simple as compared to complex mills
DISADVANTAGES
• Output is less.
• More time consuming
5. HAMMER MILL
OTHER NAMES
• Fitz Patrick comminutor
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48. GM Hamad
PRINCIPLE
• The basic principle of hammer mill is impact.
CONSTRUCTION
• The hammer mill is an impact mill using a
high-speed rotor (up to 10,000 rpm) to
which a number of swinging hammers are
fixed. A universal mill employs a variety of
rotating milling elements such as a pin
disk, wing or blade beater, turbine rotor,
or hammer-type rotor, in combination
with either a matched pin disk (that may
or may not rotate), or perforated screen or stator.
• Criticality: The screens that retain the material in the milling chamber
are not woven but perforated. The particle size of the discharged
material is smaller than the screen hole or slot, as the particles exit
through the perforations on a path approximately tangential to the
rotor. Efforts to strengthen a screen by increasing its thickness influence
particle size. For a given rotor speed and screen opening, a thicker
screen produces a smaller particle, which is also illustrated in Fig.
WORKING
• The material is fed at the top or center, thrown out centrifugally, and
ground by impact of the hammers or against the plates around the
periphery of the casing. The clearance between the housing and the
hammers contributes to size reduction. The material is retained until it is
small enough to fall through the screen that forms the lower portion of
the casing. Particles fine enough to pass through the screen are
discharged almost as fast as they are formed.
• Some internal classification can be achieved by appropriate selection of
milling tools. The particle size that can be achieved will depend on the
type of milling tool selected, rotor speed (calculated as tip speed it the
outermost rotating part), and solid density in the mill or solid feed rate.
CRITICAL SPEED
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49. GM Hamad
• Comminution is effected by impact at peripheral hammer speeds of up
to 7,600 meters per minute, at which speed most materials behave as if
they were brittle. In the preparation of wet granules for compressed
tablets, a hammer mill is operated at 2,450 rpm with knife edges, using
circular or square holes of a size determined by what will pass without
clogging (1.9 to 2.54 cm). In milling the dried granulation, the mill is
operated at 1,000 or 2,450 rpm with knife edges and circular holes in the
screen (0.23 to 0.27 cm).
• Speed is crucial. Below a critical impact speed, the rotor turns so slowly
that a blending action rather than comminution is obtained. This results
in overloading and a rise in temperature. Microscopic examination of the
particles formed when the mill is operating below the critical speed
shows them to be spheroidal, indicating not an impact action, but an
attrition action, which produces irregularly- shaped particles.
• At very high speeds, there is possibly insufficient time between
hammers for, the material to fail from the grinding zone. In wet milling
of dispersed systems with higher speeds, the swing hammers may lay
back with an increased clearance. For such systems, fixed hammers
would be more effective.
FACTORS AFFECTING PARTICLE SIZE OF A PRODUCT
• Rotor speed
• Feed rate
• Type and number of hammers
• Clearance between hammers and chamber wall
• Discharge opening of screens
EXAMPLES
• Afex comminuting mill
• Fitz comminuting mill
PHARMACEUTICAL APPLICATIONS
• The hammer mill can be used for almost any type of size reduction. Its
versatility makes it popular in the pharmaceutical industry, where it is
used to mill dry materials, wet filter-press cakes, ointments, and slurries.
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50. GM Hamad
• A hammer mill can be used for granulation and close control of the
particle size of powders.
• They are used for preparation of wet granules for compressed tablets.
• They can be used for grinding of fibers.
• They can be used for crystalline material.
• Used in powdering the barks, leaves, roots, crystals and filter cakes.
ADVANTAGES
• They are simple to install and operate, the operation is continuous.
• They are rapid in action and many different types of materials can be
ground with them.
• There is no chance of contamination due to abrasion of metal from the
mill because no surfaces of the mill move against each other.
• The particle size of the material to be reduced can be easily controlled
by changing the speed of the rotor, hammer type, shape & size of the
screen.
• They are easy to clean and may be operated as a closed system to
reduce dust and explosion hazards.
DISADVANTAGES
• Heat buildup during milling is more, therefore, product degradation is
possible.
• Hammer mills cannot be employed to mill sticky, fibrous and hard
materials.
• The screens may get clogged. Wearing of mill and screen is more with
abrasive materials.
6. PIN MILL
PRINCIPLE
• The basic principle of pin mill is attrition.
CONSTRUCTION
• Pin mills Consist of two horizontal steel plates
with vertical projections arranged in concentric
circles on opposing faces and becoming more
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51. GM Hamad
closely spaced towards the periphery. The projections of the two faces
intermesh.
WORKING
• The feed is introduced at a controlled rate to the milling chamber
through the center of the stator and is propelled through intermeshing
rings of rotor and stator pins by centrifugal motion. The passage
between the pins leads to size reduction by impact and attrition. The
material is collected in the annular space surrounding the disks and
passes to a separator. The large volumes of air drawn through the mill
are discharged through the separator. The final particle size achieved in
a pin mill is governed by the rotor speed, solids feed rate, and air flow
rate through the mill.
• Smaller particles can be generated by maxi-mizing the rotor tip speed
and minimizing both product feed and air flow rate. The fineness of the
grind may be varied by the use of disks with different dispositions of
pins. As equipment scale is increased, maintaining rotor tip speed is one
reliable way to achieve milled particle sizes comparable to small-scale
results.
ADVANTAGES AND DISADVANTAGES
• Absence of screens and gratings provides a clog-free action.
• This type of milling is typically able to achieve smaller average particle
size than wet rotor-stator milling.
• The machine is suitable for grinding soft, non-abrasive powders, and low
milling temperatures permit heat-sensitive materials to be processed.
7. BALL MILL
OTHER NAMES
• Jar mill
PRINCIPLE
• The basic principle of ball mill is impact and attrition.
VARIANTS OF SIMPLE BALL MILL
TUBE MILL
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52. GM Hamad
• The tube mill as its name implies has a long narrow cylinder and can
grind to a finer product than the conventional ball mill.
PEBBLE MILL
• If pebbles are used, it is known as a pebble mill.
ROD MILL
• If rods or bars are used, it is known as a rod mill. The rod mill is
particularly useful with sticky material that would hold the balls together
because the greater weight of the rods causes them to pull apart.
HANDING MILL
• The ball mill may be modified to a conical shape and tapered at the
discharge end. If balls of different size are used in a conical ball mill, they
segregate according to site and provide progressively finer grinding as
the material flows axially through the mill.
CONSTRUCTION
• The ball mill consists of a horizontally rotating hollow
vessel of cylindrical shape with the length slightly greater
than its diameter. The mill is partially filled with balls of
steel or pebbles, which act as the grinding medium.
BALLS
• The balls act as grinding medium. Balls are usually made up of stainless
steel or steel and occupy about 30 to 50% of the volume of cylinder.
• Balls are made up of:
- Porcelain
- Flint
- Nylon
- Rubber
METALLIC FRAME
• The cylindrical vessel is mounted on a metallic frame.
HANDLE
• It is needed for rotating the cylinder.
WORKING
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53. GM Hamad
• The material to be grounded is put into the mill through the lid. The mill
is rotated at a slow speed for appropriate time until the desired size
reduction is achieved. The product is then taken out and passed through
the suitable sieve to get powder of desired size range.
• Most ball mills utilized in pharmacy are batch-operated, however,
continuous ball mills are available, which are fed through a hollow
trunnion at one end, with the product discharged through a similar
trunnion at the opposite end. The outlet is covered with a coarse screen
to prevent the loss of the balls.
CRITICAL SPEED
• The critical speed of a ball mill is the speed at which the balls just begin
to centrifuge with the mill.
• In a ball mill rotating at a slow speed, the balls roll and cascade over one
another, providing an attrition action.
• As the speed is increased, the balls are carried up the sides of the mill
and fall freely onto the material with an impact action, which is
responsible for most size reduction. If the speed is increased sufficiently,
the balls are held against the mill casing by centrifugal force and revolve
with the mill.
critical speed = 76.6/√D
• Improving the efficacy of ball mill
• Efficiency of a ball mill is increased as amount of material is increased
until the space in the bulk volume of ball charge is and then, the
efficiency of milling is by further addition of material.
• Increasing the total weight of balls of a given size increases the fineness
of the powder. The weight of the ball charge can be increased by
increasing the number of balls or by using a ball composed of a material
with a higher density.
• Optimum milling conditions are usually obtained when the bulk volume
of the balls is equal to 50% of the volume of the mill, variation in weight
of the balls is normally affected by the use of materials of different
densities. Thus, steel balls grind faster than porcelain balls, as they are
three times denser.
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54. GM Hamad
• Wetting agents may increase the efficiency of milling and physical
stability of the product by nullifying electrostatic forces produced during
comminution. For those products containing wetting agents, the
addition of the wetting agent at the milling stage may aid size reduction
and reduce aggregation.
USES
• Used for either wet or dry milling
• Ball mill at low speed is used for milling dyes, pigments and insecticides.
• Stainless steel balls are preferred in production of ophthalmic and
parenteral products.
ADVANTAGES
• Ball mill has the advantage of being used for batch or continuous
operation.
• In a batch operation, unstable or explosive materials may be sealed
within an inert atmosphere and satisfactorily ground.
• Ball mills may be sterilized and sealed for sterile milling in the
production of
• The installation, operation, and labor costs involved in ball milling are
low.
DISADVANTAGES
• The ball mill is very noisy machine.
• Ball mill is a slow process.
• Soft, tacky, fibrous material cannot be milled by ball mill.
8. FLUID-ENERGY MILL
OTHER NAMES
• Jet mill or micronizer
PRINCIPLE
• The basic principle of fluid-energy mill is impact and attrition.
CONSTRUCTION
• A fluid-energy mill consists of following parts:
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55. GM Hamad
- Venturi injector
- Nozzles
- Grinding chamber
- Discharge outlet
- Cyclone separator
- Bag collector
• The design of the fluid-energy mill provides
internal classification, which permits the finer
and lighter particles to be discharged and the
heavier oversized particles, under the effect of centrifugal force, to be
retained until reduced to a small size.
WORKING
• In the fluid-energy mill or micronizer, the material is suspended and
conveyed at high velocity by air or steam, which is passed through
nozzles at pressure of 100 to 150 pounds per square inch (psi). The
violent turbulence of the air and steam reduces the particle size chiefly
by inter-particular attrition. Air is usually used because most
pharmaceuticals have a low melting point or are thermolabile. As the
compressed air expands at the orifice, the cooling effect counteracts the
heat generated by milling.
• The material is fed near the bottom of the mill through a venturi injector
(A). As the compressed air passes through the nozzles (B), the material is
thrown outward against the wall of the grinding chamber (impact) (C)
and other particles (attrition). The air moves at high speed in an elliptical
path carrying with it the fine particles that pass out of the discharge
outlet (D) into a cyclone separator and a bag collector. The large
particles are carried by centrifugal force to the periphery, where they
are further exposed to the attrition action.
USES
• It is used to reduce particle size of antibiotics and vitamins.
• Moderately hard materials can be processed for size reduction.
• Ultra-fine grinding can be achieved.
ADVANTAGES
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56. GM Hamad
• Powders with all particles below a few micrometers may be quickly
produced by this method.
• Cooling effect of grinding fluid as it expands in the chamber
compensates for the moderate heat generated during grinding process.
• Narrow range of particle size produced.
• No abrasion of the mill.
• For very sensitive materials, an inert gas can be used.
• Useful for thermolabile substances e.g. vitamins and enzymes.
DISADVANTAGES
• The disadvantage of high capital and running costs may not be so serious
in the pharmaceutical industry because of the high value of the
materials which are often processed.
• One drawback of this type of mill is the potential for build-up of
compressed product in the mill or on the classifier. This can affect milled
particle size by changing the open volume in the mill or open area in the
classifier, especially if classifier vanes or gas nozzles become plugged or
blocked.
9. DISINTEGRATOR
PRINCIPLE
• It works on the principle of impact and grinding.
CONSTRUCTION
• It consists of:
- Chamber
- Disc and shaft
- Sieve
- Hopper
• The disintegrator consists of a drum
shaped chamber made up of steel. In the chamber, there are four steel
beaters fixed to a disc through which passes a shaft which rotates at a
higher speed up to 5000-7000 rpm. The tower part of the chamber is
filled with a desired number sieve which can be easily attached or
detached. A hopper is attached at the upper surface of the chamber.
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57. GM Hamad
WORKING
• The drug to be comminuted is fed into the chamber through the hopper
where it is broken by the direct blow of the beaters and by the impact of
the material, which is thrown with a great force against the surface of
the chamber. The reduced particles pass through the sieve of desired
size.
ADVANTAGES
• Can be used for powdering very bard drugs.
• Used for powdering crude vegetable drugs.
• Can be used for milling the ointments and for mixing the powdered
ingredients.
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58. GM Hamad
MIXING
DEFINITION
“Mixing is a process that tends to result in a randomization of dissimilar
particles within a system.” (OR)
“The process in which two or more than two components in a separate or
roughly, mixed conditions is treated in such a way that each particle of anyone
ingredient lies as nearly as possible to the adjacent particles of other
ingredients is called mixing.”
OBJECTIVES OF MIXING
• To ensure uniformity of composition between mixed ingredients.
• To initiate or enhance physical or chemical reactions e.g. diffusion and
dissolution.
• To improve single phase and multiple phase system.
• To control heat and mass transfer.
RESULT OF MIXING
• When two or more than two miscible liquids are mixed true solutions
are obtained.
• When two immiscible liquids are mixed in the presence of emulsifying
agent, emulsions are produced.
• When a solid is mixed in a vehicle a solution is obtained.
• When an insoluble solid is mixed in a vehicle a suspension is obtained.
• When a solid/liquid is mixed in a semisolid base/ointment suppositories
are produced.
• When two or more than two solids are mixed together a solid dosage
form is obtained.
TYPES OF MIXTURES
1. POSITIVE MIXTURES
• Spontaneous, irreversible and complete mixing of two or more than two
gases or miscible liquids through diffusion, without the expenditure of
energy results in a positive mixture.
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59. GM Hamad
2. NEGATIVE MIXTURES
• These are formed when insoluble solids are mixed with a vehicle to for a
suspension or when two immiscible liquids are mixed to form emulsion.
• These mixers require a high degree of mixing with external force.
3. NEUTRAL MIXTURES
• The components of neutral mixers do not have the tendency to mix
spontaneously but once mixed, they do not separate out immediately
e.g. ointments, pastes.
• Neither mixing nor de-mixing unless system is acted upon by an external
energy input.
DEGREE OF MIXING
• Degree of mixing is defined in terms of standard deviation.
Standard deviation = √
xy
N
• Here,
- x and y are proportions of the major and minor constituents, N is
the number of particles in the sample taken.
• Mixing of powder should be continued until the amount of active drug
that is required in a dose is with in ± 35° of that found by assay in a
representative number of sample doses.
MECHANISM OF MIXING
• In all type of mixers mixing is achieved by applying one or more of the
following mechanisms:
1. CONVECTIVE MIXING
• During convective mixing, transfer of groups of particles in bulk take
place from one part of the powder bed to another.
2. SHEAR MIXING
• During shear mixing, shear forces are created within the mass of the
material by using agitator arm or a blast of air.
3. DIFFUSIVE MIXING
• During this mixing, the material are tilted so that the gravitational forces
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60. GM Hamad
causes the upper layers to slip and diffusion of the individual particles
take place over newly developed surfaces. Mixing occur by diffusion
process by random movement of particle within a powder bed and
cause them to change their relative position.
CLASSIFICATION OF MIXING EQUIPMENTS
POWDER MIXERS / SOLID MIXERS
1. Pestle and Mortar
2. Spatula
3. Sieves
4. Tumbler Mixers
a) Cube Mixers
b) V Mixers
c) Double Cone/H type
d) Y Mixers
5. Agitator Mixers
a) The Ribbon Blender
b) Helical Flight Mixer
c) Monastery Blender
d) Paddle Mixer
e) Granulating Mixer
f) Trough Mixer
FLUID MIXERS / LIQUID MIXERS
1. BATCH MIXERS
a. Shaker Mixer
b. Impellers
i. Propeller Mixer
ii. Turbine Mixer
- Pitched Blade Turbine
- Curved Blade Turbine
- Disk Style Turbine
iii. Paddle Mixer
- Simple Paddle
- Gate Paddle
- Anchor Paddle
- Helix Paddle
c. Air Jets
d. Fluid Jets
2. CONTINUOUS MIXERS
a. Baffled Pipe Mixers
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61. GM Hamad
b. Mixing Chamber
c. Continuous Mixing Tank
SEMI-SOLID MIXERS
1. Agitator Mixers / Kneaders
2. Shear Mixers / Mulling Mixers
3. Ultrasonifiers
POWDER MIXING
INTRODUCTION
• Powder mixing is a process in which two or more than two solid
substances are mixed in a mixer by continuous movement of particles.
• It is a neutral type mixing and is one of the most common operations
employed in pharmaceutical industries for the preparation of different
types of formulations e.g. powders, capsules.
FACTORS AFFECTING POWDER MIXING
1. MIXING FACTORS
• Powder mixing operation is quite different from that of liquid. Following
factors must be considered:
A. VOLUME
• Sufficient space should be provided during mixing for dilation of the bed
overfilling of the mixer reduces the efficiency of mixing. The mixer
should not be full to the brim.
B. MIXING MECHANISM
• The mixer selected for mixing must apply suitable shear forces and
convective movement so that the whole of the material passes through
the mixing area.
C. DURATION OF MIXING
• Mixing of powders must be done for optimum time for any particular
situation.
D. HANDLING OF MIXED POWDERS
• After mixing the powders, they should be handled in such a way that the
separation of ingredients in minimized.
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62. GM Hamad
• Sometimes vibration caused by subsequent manipulation, transport,
handling or use is likely to cause segregation.
2. PHYSICAL PROPERTIES / FACTORS
A. MATERIAL DENSITY
• If the density of mixing ingredients is different, the denser material will
sink through the lighter one forming a layer at the bottom resulting in
improper mixing.
B. PARTICLE SIZE
• Variation in particle size can lead to segregation since smaller particles
can fall through the voids between the larger particles.
C. PARTICLE SHAPE
• Spherical shape of particle is ideal for mixing the powders and any
deviation from this shape leads to difficulty in mixing. However, once the
mixing has been done, the particles with irregular shapes can interlock
with each other, reducing the chance of segregation.
D. PARTICLE ATTRACTION
• Some particles exert electrostatic charges due to which the particles of
one powder may attract to particles of another powder leading to
aggregation of particles.
E. PROPORTION OF THE MATERIALS TO BE MIXED
• It is easy to mix powders if they are available in equal quantities but it is
difficult to mix small quantities of powders with large quantities of other
ingredients or diluents.
MECHANISM OF POWDER MIXING
• Powder mixing proceeds by a combination of one or more underlying
mechanisms:
1. CONVECTIVE MOVEMENTS OF POWDER BED
• It is caused by an invasion of powder bed that occurs due to the
movement of relatively larger mass of material from one part of powder
bed to another. It is analogous to bulk transport. It is done by means of
blades, paddles and screws.
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63. GM Hamad
2. SHEAR MIXING
• When shear occurs between regions of different composition and
parallel to their interface, it reduces the scale of segregation by thinning
the dissimilar layers.
• Shear occurring in a direction normal to the interface of such layers is
also effective since it too reduces the scale of segregation.
• In addition, large or irregular grains of powder tend to be expelled from
regions of high shear through a mechanism shear induced migration.
3. DIFFUSE MOVEMENTS (DISPERSION)
• The random motion of powder within a particular bed cause them to
change position relative to one another. Such an exchange of position by
single particles results in reduction of the intensity of segregation. Most
efficient mixers operate to induce mixing by all three mechanisms.
Diffusion is rate limiting mechanism for powder mixing.
EQUIPMENTS FOR POWDERS MIXING
1. PESTLE AND MORTAR
• It is the most commonly used equipment for small scale mixing,
especially in compounding prescriptions. In this method, particle size
reduction and mixing is done in a single operation.
2. SPATULA
• This method is relatively insufficient but is used when compaction
produced by pestle and mortar method is undesirable.
3. SIEVES
• Sieves are generally used for breaking the loose aggregates of powders
in pre or post mixing operation so as to increase overall effectiveness of
a blending technique. Sometimes powder may have to be passed a
number of times through the sieve to get a homogenous powder.
4. TUMBLER MIXER (BLENDER)
• These mixers are used for large scale mixing or batch mixing of powders.
The efficiency of tumbling mixer is highly dependent on the speed of
rotation. Rotation that is too slow that does not produce the desired
intense tumbling or cascading motion nor does it generate rapid shear
rates. The rotation that is too rapid tends to produce centrifugal force
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64. GM Hamad
sufficient to hold the powders to the sides and thereby reducing
efficiency. Speed of rotation commonly ranges from 30-100rpm.
• The optimum rate of rotation depends upon:
- Size and the shape of tumbler
- Type of material being mixed
• Tumbler mixer consists of a container which is mounted so that it can be
rotated about an axis. The resulting tumbling motion is accentuated by
means of baffles or simply by virtue of shape of container.
• Mostly an eight-angle shaped tumbler is used with baffles on each side.
Granules are twisted, flowing along the angle of baffle and mixed again
by the center short baffle. It can give best mixing result.
PRINCIPLE
• The mixers work on the principle of:
- Convective movement
- Shear mixing
WORKING
• In tumbler mixers rotation of vessel imparts movement to the materials
by tilting the powders until the angle of surface exceeds the angle of
repose when the surface layers of particles go into a slide and the
material is tumbled, rolled and folded e.g. in case of Y-cone blender.
• Plain of shear is always changing throughout the mass and the moving
material is constantly re divided and recombined.
CONSTRUCTION
METALLIC CONTAINER
• It consists of metallic vessel of various shapes rotating about its mid-
point on horizontal axis. Depending upon shape of vessel, they could be:
I. Cube mixer
II. V mixer
III. Double cone mixer
IV. Y mixer
MOTOR
• Horizontal axis is rotated with the help of motor.
I. CUBE MIXER
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65. GM Hamad
• It consists of a cube shaped stainless steel drum which is connected to
motor, blades are also attached inside the container to reduce the size.
The cube has an opening in front with screw nuts. It is good for wet
granulation mixing.
II. TWIN SHELL BLENDER V-SHAPED
• This is most popular mixer used in industry. When this is rotated, the
material is collected in the bottom of V, splits into two portions when V
is inverted. This design is quite effective because shear forces are
enhanced. Facilitate asymmetric rotation.
III. H-TYPE MIXERS / DOUBLE CONE MIXER
• It consists of mixing blades which rotates inside the pan with the help of
electric motor. Material is put in the pan and mixed by rotating blades.
Cover of pan is transparent and operation can be viewed.
IV. Y-CONE BLENDER
• It has a shallow drum with conical portion, the smaller end of which
provides discharge opening and longer end has two cylindrical portions
mounted approximately at right angles to each other.
WORKING
• Sliding material is deflected by inclined curved surface as there is
continuously changing angle to achieve the current in both vertical and
horizontal directions which is essential feature of efficient mixing.
• The gentle force is free from attrition it does not breakup crystal shape
and does not result in change of particle size and neither does it
generates heat.
• In case of Y-shaped cone blender, 2-fold force/reaction occurs;
- Rolling and folding movements
- Continuous dividing and recombining of powder.
• By its unique geometrical consideration; all internal substances blend
with each other.
ADVANTAGES
• Tumbler mixers are designed for rapid, economical blending of powders,
colors, resins, granules etc.
• It does not change the particle size distribution
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• It has useful application in pharmaceutical food, cosmetics production,
detergents, insecticides and explosive materials
• It does not break up the crystal shape
• It can be used for heat sensitive materials.
DISADVANTAGES
• It cannot perform wet mixing.
• Cube mixer is less efficient than paddle mixer.
5. AGITATOR MIXERS
PRINCIPLE
• The mixing is done by means of mixing screws, paddles or blades. The
high shear forces are setup during the process which break the lumps or
aggregates and produce homogenous mixture.
• They consist of a stationary container, with a horizontal or vertical
agitator moving inside it. The agitator may take the form of blade,
paddles or screws.
• They are used for mixing of wet solids. Also used for sticky or plastic
state.
TYPES
• Well known mixers of this type include:
1. The ribbon blender
2. Helical flight mixer
3. Monastery blender
4. Paddle mixer
5. Granulating mixer
6. Trough mixer
I. RIBBON BLENDER
• It is also known as conventional mixer. It consists of a horizontal
cylindrical tank usually opening at the top and fitted with helical blades.
The blades are mounted on a shaft through the long axis of the tank and
are often of both right- and left-hand twist.
• It is used for dry granules, wet granules, dry powders and semi-solids.
CONSTRUCTION
• TROUGH
- These are stationary container of welded stainless steel and of
such shapes ass to eliminate the cervices, trough are robust and
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polished from inside and outside so that they may rapidly be
cleaned.
• LID WITH COVER
- A polished stainless-steel lid is fitted with a safety grind with an
inspection cover.
• RUBBER GASKET
- Lid seats on the trough with a rubber gasket and held together
with two toggle fasteners.
• AGITATOR
- Mixer is fitted with a polished stainless-steel paddle type agitator
which is suitable for dry or moistened material. In cases where
mass becomes sticky, special agitator ribbon blender are
recommended.
• AGITATOR SHAFT
- It passes through the long axis of tank. The shaft entering the
trough is sealed by means of gasket so that dust can be avoided
and lubricant from bearing can effectively be preventing from
reaching and contaminating the mixture. When shaft is rotated,
the material is picked up by the helical blades which are then split
back.
• MOTOR
- It is fitted with a 3-phase gear motor unit that rotates the shaft.
WORKING
• The material to be mixed is put in the mixer and mixed for optimum
time period. Then the lid lifted by hand for discharge. The lid is fitted
with an electrical limit switch which prevents the agitator being in
motion with the lid raised.
II. HELICAL FLIGHT MIXER
• Powders are lifted by a centrally located vertical screw and allowed to
cascade to the bottom of the tank.
III. TROUGH MIXERS
• These are most commonly in the form of trough in which an arm rotates
and transmits shearing force to particles.
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FACTORS AFFECTING MIXER SELECTION
1. MEASURE OF DEGREE OF MIXING
• In case of powder mixing, mixer selection also depends on quantitative
measure of the degree of mixing. This is generally accomplished by the
arbitrary choice of a statistical function that indicates the uniformity of
composition of the powder bed.
2. TIME AND POWER CONSUMPTION
• Unlike most liquid mixers, solid mixers can be made to produce good
mixtures, when they are operated incorrectly, simply by mixing for a
long period of time. The mixture reaches an equilibrium state of mixing
that is the function of speed of operation of mixer.
• Minimum power is that required to operate the mixer for the time
necessary to reach a satisfactory steady state.
3. PHYSICAL PROPERTIES OF MATERIAL
• Physical properties of material greatly influence the selection of mixers.
4. ECONOMIC CONSIDERATIONS
• Economic considerations should be taken before selecting a mixer.
FLUID MIXING
INTRODUCTION
• Liquid mixing may be divided into two groups:
1. MIXING OF LIQUID AND LIQUID
- Mixing of two immiscible liquids
- Mixing of miscible liquids
2. MIXING OF SOLIDS AND LIQUIDS
- Mixing of liquid and soluble solids
- Mixing of liquid and insoluble solids
THEORY
• Mixing occurs in two stages:
1. LOCALIZED MIXING
- In which shear applied to the particles of the liquid.
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2. GENERALIZED / BULK MIXING
- Sufficient to take all the particles of the materials through the
shearing zone so as to produce a uniform product.
1. MIXING OF LIQUID AND LIQUID
A. MIXING OF TWO MISCIBLE LIQUIDS
• Mixing of two miscible liquids is caused by diffusion. Simple shaking and
stirring is enough but if the liquids are not readily miscible or if they have
very different viscosities then electric stirrer may be used.
B. MIXING OF TWO IMMISCIBLE LIQUIDS
• When two immiscible liquids are mixed together in the presence of an
emulsifying agent, an emulsion is formed. For the production of a stable
emulsion, mixing must be continuous without ceasing because the
components tend to separate out if continuous work is not applied on
them.
2. MIXING OF LIQUIDS AND SOLIDS
A. MIXING OF LIQUIDS AND SOLUBLE SOLIDS
• In this case, soluble solids are dissolved in a suitable liquid by means of
stirring. It is a physical change.
B. MIXING OF LIQUIDS AND INSOLUBLE SOLIDS
• When insoluble solids are mixed with a vehicle, a suspension is produced
which is an unstable system the ingredients of a suspension out when
allow to stand for some time therefore to get a good suspension a
suitable suspending agent should be used.
MECHANISM OF FLUID MIXING
• Fluid mixing involve more than one following mechanisms.
1. BULK TRANSPORT
• The movement of relatively large portion of the material being mixed
from one location of the system to the constitutes bulk transport. This is
usually accomplished by means of paddles, revolving blades or other
devices within the mixer arranged so as to move adjacent volumes of
the liquid in different direction thereby shuffling the system in different
directions.
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