UNIT OPERATIONS : PHARMACEUTICAL ENGINEERING ON BASICS AND APPLICATION

BASICS AND
APPLICATION OF
Submitted for
Teaching Assistantship
PH 101
By
Atanu Barik
M. Pharm
Dept. of Pharmaceutical Engg .& Tech.
Indian Institute of Technology (BHU)

OVERVIEW
• Introduction
• History and Background
• Unit Operation and Unit Process
• Classification
• Application

INTRODUCTION
Unit Operations gives idea about
• specific physical operation;
• different equipments-its design,
• material of construction and operation;
• calculation of various physical parameters (mass flow, heat
flow, mass balance, power and force etc.).
In Pharmaceutical Engineering a unit operation is a basic step
in a process.
Unit operations involve a physical change or chemical
transformation such as separation, crystallization, evaporation,
filtration, polymerization, isomerization, and other reactions.

History and Background
Arthur Dehon Little propounded
the concept of "unit operations"
to explain industrial chemistry
processes in 1916.
01
In 1923, William H. Walker, Warren K.
Lewis and William H. McAdams wrote
the book The Principles of Chemical
Engineering and explained that the
variety of chemical industries have
processes which follow the same
physical laws.
02

Classification
1
Flow of
Fluid
2
Heat
and
Mass
Transfer
3
Filtration
4
Centrifugation
5
Size
Reduction
6
Mixing
of Solids
7
Extraction
8
Distillation
9
Evaporation
10
Crystalization
11
Drying

1. FLOW OF FLUIDS
• It is the flow of substance that does not permanently resist distortion.
Fluid Dynamics
• Fluid dynamics is a subdiscipline of fluid mechanics that describes the flow of fluids—liquids and gases.
 Applications of Fluid dynamics
• calculating forces and moments on aircraft,
• determining the mass flow rate through pipelines,
• predicting weather patterns,
• understanding nebulae in interstellar space and modelling fission weapon detonation.
 The solution to a fluid dynamics problem typically involves the calculation of various properties of the fluid, such as flow
velocity, pressure, density, and temperature, as functions of space and time.
Thermodynamic equation:
where p is pressure, ρ is density, T the absolute temperature, while Ru is the gas constant and M is molar mass for a
particular gas.

• Compressible vs incompressible flow
• Compressible Flow of fluid or gas is the changes in density in changes of pressure
or temperature.
• However, in many situations the changes in pressure and temperature are
sufficiently small that the changes in density are negligible. In this case the flow
can be modelled as an incompressible flow. Otherwise the more general
compressible flow equations must be used.
• Newtonian vs non-Newtonian fluids
• All fluids are viscous, meaning that they exert some resistance to deformation:
neighboring parcels of fluid moving at different velocities exert viscous forces on
each other.
• Isaac Newton showed that for many familiar fluids such as water and air, the
stress due to these viscous forces is linearly related to the strain rate.
• Non-Newtonian fluids have a more complicated, non-linear stress-strain
behaviour. The sub-discipline of rheology describes the stress-strain behaviours
of such fluids, which include emulsions and slurries, some viscoelastic materials
such as blood and some polymers, and sticky liquids such as latex, honey and
lubricants.

• Reynolds number
• It is used for measurement and type of flow determination.
Re = D× u × density of liquid/Viscosity of fluid
D = diameter of pipe, u = Average velocity
• When Re<2000 then flow is laminar or viscous or streamline
Re>4000 then flow is turbulent
Re is 2000–4000 then flow is laminar or turbulent
• Critical velocity
• It is defined as average velocity of any fluid at which viscous flow changes into turbulent flow.
• Manometers
• These are the devices which are use for measuring the pressure difference.
1. Simple manometer: It helps in measuring the consumption of gases in the chemical reaction.
2. Differential manometer (two-fluid U-tube manometer): It useful for measuring small gas
pressure.

Bernoulli’s Theorem
• Within a horizontal flow of fluid, points of higher fluid speed will
have less pressure than points of slower fluid speed.
• Bernoulli's principle: At points along
a horizontal streamline, higher pressure
regions have lower fluid speed and lower
pressure regions have higher fluid speed.
• The variables P1, v1, h1 refer to the pressure, speed, and height of the fluid at
point 1, whereas the variables P2, v2, h2 refer to the pressure, speed, and height
of the fluid at point 2 as seen in the diagram below.

Measurement of rate of
flow of fluids
1. Direct weighing or measuring
2. Hydrodynamic methods

Pumps
These are mechanical
devices use to increase
the pressure energy of a
liquid.
A. Reciprocating pumps: These are
used for injection of inhibitors in
polymerization units and
corrosion inhibitors
to high pressure system.

C. Peristaltic pump: It contains silicone
rubber tube in a U-shape against roller is
clamped.
Use:
It is used for pumping emulsions, creams in
pharmaceutical industry and pumping
parenteral nutrition infusions to patient and
blood pumping for surgical operation.

Chapter 2
Heat and Mass Transfer

2. HEAT & MASS TRANSFER
• Heat flow from high region temperature to lower region temperature. According to
principle of thermodynamic, whenever physical or chemical transformation occurs, heat
flows into or leaves the system.
• Mechanism
1. Conduction
When heat flow in body is achieved by transfer of momentum of individual atoms or
molecule without mixing. This mechanism is based on Fourier’s law.
• Fourier’s law
• It states that the rate of heat flow through a uniform material is proportional to the area
and temperature drop and inversely proportional to length of path of flow.

Mechanism
• 2. Convection
A. Forced convection
• When mixing of fluid is achieved by use of agitator or stirrer or
pumping the fluid for recirculation, such process in heat transfer is
called forced convection.
• In force convection, the stagnant films (film or surface coefficients)
are of great importance in determining rate of heat transfer.
• Film coefficient is the quantity of heat flowing through unit area of
film for unit drop in temperature.

B. Natural convection
• Mixing of fluid is accomplished by the currents set up, when body of
fluid is heated. Such process is known as natural convection.
• Fluid circulation caused by change in the density due to temperature
difference in the fluid which depends on:
Geometry of the system (size, shape and arrangement of heating
surface).
Shape of vessel in which the fluid is enclosed.
 This natural convection is observed when extracts are
evaporated in open pans.

3. Radiation
• Radiation is a process in
which heat flows through
space by means of
electromagnetic waves.
• Thermal radiation Heat
transfer by radiation is
known as thermal
radiation.
• Various forms of emitters
used for the supply of
radiant energy are given
below:

 Black body
Grey body
It is defined as that
body whose
absorptivity is
constant at all
wavelength of
radiation, at given
temperature.
It is defined as a body that radiates maximum possible
amount of energy at given temperature.
Normally, hot bodies emit radiation. Stephen-Boltzmann
law gives the total amount of radiation emitted by black
body.
q = Bat4
q = energy radiated per second
A = area of radiating surface
T = absolute temperature of radiating Surface
b = constant
When emissivity is equal to absorptivity then substance is
considered as black body.

• CONVEYOR
• Belt Conveyors
• A belt conveyor system consists of two or more
pulleys (sometimes referred to as drums), with
an endless loop of carrying medium—the
conveyor belt—that rotates about them.
• A conveyor belt is the carrying medium of a belt
conveyor system (often shortened to belt
conveyor).
• Screw Conveyor
• A screw conveyor or auger conveyor is a
mechanism that uses a rotating
helical screw blade, called a "flighting", usually
within a tube, to move liquid or granular
materials.

• CONVEYOR
• Pneumatic conveyors
• Pneumatic conveyors are
continuous conveyors for
bulk material in which
material is conveyed
in an enclosed tube system
by means of compressed
air or by means of a
vacuum.

• Chain Conveyors
• A chain conveyor is a type of
conveyor system for moving
material through production
lines.
• Chain conveyors are
primarily used to transport
heavy unit loads, e.g. pallets,
grid boxes, and industrial
containers.

• CONVEYOR
• Bucket Conveyors
• Bucket conveyors consist of
endless chains or belts to
which are attached buckets to
convey bulk material in
horizontal, inclined, and
vertical paths.
• The buckets remain in
carrying position until they
are tipped to discharge the
material.

3. FILTRATION • Factors Affecting Filtration
Filtration is affected by the characteristics of the slurry,
including:
1. The properties of the liquid , such as density,
viscosity, and corrosiveness.
2. The properties of the solid, for example, particle
shape, particle size, particle size distribution, and
the rigidity or compressibility of the solid.
3. The proportion of solids in the slurry.
4. Whether the objective is to collect the solid, the
liquid ,or both.
5. Whether the solids have to be washed free from
the liquid or a solute
*The suspension of solid and liquid
to be filtered is known as the
slurry. The porous medium
used to retain the solids is
described as the filter medium;
* The accumulation of solids on the
filter is referred to as the filter
cake, while the clear liquid
passing through the filter is the
filtrate.

3. FILTRATION
Mechanism of Filtration
1. Straining: It is similar to sieving,
means the particles of larger size
cannot pass through the smaller pore
size of filter medium.
2. Impingement: Solids move with
streamline flow and strike the filter
medium.
3. Entanglement: Particle becomes
entangled in mass of fiber due to small
size of particle than pore size.
4. Attractive force: Solids are retaining
due to attractive forces between
particles and filter medium.
It is process of separation of solids
from fluid by passing the same
through porous medium that retain
the solids, but allows the fluid to
pass through.
Types of Filtration
1. Surface filtration (Screen filtration): E.g.,
Membrane filter
2. Depth filtration: E.g., Ceramic filter,
sintered filter
3. Cake filtration: E.g., Filter cake made
from diatomite

”Filter Aids”
• Filter Aids is a group of inert materials that can be used in filtration pretreatment.
• There are two objectives related to the addition of filter aids.
• One is to form a layer of second medium which protects the basic medium of the system.
• This is commonly referred to as “precoat”.
• The second objective of filter aids is to improve the flow rate by decreasing cake
compressibility and increasing cake permeability.
• This type of usage is termed as “admix” or “body feed”.
• Example- Purified talc, siliceous earth (kieselgurh), clays, charcoal, paper pulp, magnesium
carbonate, bentonite, silica gel

Filter paper
• Filter paper is a semipermeable
paper barrier placed
perpendicular to a liquid or air
flow. It is used to separate fine
solids from liquids or air.
• The important parameters are
wet strength, porosity, particle
retention, flow rate,
compatibility, efficiency and
capacity.

Types of laboratory filter papers
• 1.Qualitative Filter Papers
• 100% cotton linter cellulose
• pH tolerant: 0 to 12
• Thermostable: up to 120°C
• Ash Content: 0.1%
▫ APPLICATIONS
• Clarify and remove precipitates
• Preparation for qualitative
analysis
• 2.Quantitative/Hardened Filter Papers
• 100% cotton linter cellulose
• Ash Content: 0.01%
• Acid washed: Double acid washed in
hydrochloric then hydrofluoric acid, then
rinsed with ultrapure water to neutralize.
▫ APPLICATIONS
• Gravimetric analysis
• Environmental monitoring

Types of laboratory filter papers
Other Filtering materials
1. Cotton filters
2. Glass-wool filters
3. Sintered glass filters
4. Funnels
3.Chromatography Papers
• High quality papers are carefully tested
for spot formation, capillary action, water
flow rate and absorption speed to assure
uniformity and reproducibility
• Better resolution with slower flow rate
papers
APPLICATIONS
• Chromatography
• Electrophoresis and blotting
• Separation of heavily loaded solutes

Rate of Filtration
• All other things being equal, the object of the operation is to filter the
slurry as quickly as possible.
• The factors affecting rate of filtration is known as Darcy”s law and
may be expressed as:
• dV / dt = KA P /ul
• where V= volume of filtrate, t = time of filtration , K = constant for
the filter medium and filter cake , A = area of filter medium , P =
pressure drop across the filter medium and filter cake , u = viscosity
of the filtrate , and l = thickness of cake.

Industrial Filters
• Four groups may be listed:
• A- Gravity filters. B- Vacuum filters
• C- Pressure filters. D- Centrifugal filters.
• A-Gravity filters,
• Employing thick granular beds
are widely used in water
filtration e.g. Sand Filter

B- Vacuum filters
Vacuum filters operate practically at higher pressure differentials
than gravity filters.
Rotary vacuum filter and the leaf filter are most extensively used.
The leaf filter:
• The leaf filter is consisting of a frame enclosing a drainage
screen or grooved plate , the whole unite being covered with filter
cloth.
• The outlet for the filtrate connects to the inside of the
frame, the general arrangement is shown in the Fig. which
represents a vertical section through the leaf. The frame
may be circular, square or rectangular shapes.
The operation: The leaf filter is immersed in the slurry and a
receiver and a vacuum system connected to the filtrate outlet.

C. Rotary vacuum filter (Rotary filter)
It is a metal cylinder mounted horizontally,
the curved surface being a perforated plate,
supporting a filter cloth. Internally, it is
divided into several sectors and a separate
connection is made between each sector
and a special rotary valve.
The rotary filter is continuous in operation
and has a system for removing the cake
that is formed , so, it is suitable for use with
concentrated slurries.

C- Pressure Filters:
Due to the formation of cakes of low
permeability, many types of slurry
require higher pressure difference for
effective filtration than can be
applied by vacuum techniques.
Pressure filters are used for such operations.
However, high operational pressures, may
prohibit continuous operation because of the
difficulty of discharging the cake whilst the
filter is under pressure.
Examples are the sweetland filter, plate
and frame filter press.

D- Centrifugal Filters
A centrifuge consists of a basket in which
mixture of solid and liquid , or mixture of
two liquids is rotated at high speed so that
it is separated into its constituents by the
action of centrifugal force.
Types of baskets:
A- Imperforated, in which the liquid is
removed through a skimming tube ,
while the solid particles, sediment to
the wall.
In pharmacy, the centrifuge is commonly used
for drying crystals and for separating emulsions into
their constituent liquids.
B- Perforated basket in which the
liquid passes out through the holes.

4. CENTRIFUGATION
• Centrifugation is a technique
of separating substances
which involves the application
of centrifugal force.
• The particles are separated
from a solution according to
their size, shape, density,
viscosity of the medium and
rotor speed.
Definition
It is a unit operation employed for
separating the constituents present
in dispersion with aid of centrifugal
force.

Theory of Centrifugation
• In a solution, particles whose density is higher than that of
the solvent sink (sediment), and particles that are lighter than
it float to the top.
• The greater the difference in density, the faster they move. If
there is no difference in density (isopyknic conditions), the
particles stay steady.
• To take advantage of even tiny differences in density to
separate various particles in a solution, gravity can be
replaced with the much more powerful “centrifugal force”
provided by a centrifuge.
• A centrifuge is a piece of equipment that puts an object in
rotation around a fixed axis (spins it in a circle), applying a
potentially strong force perpendicular to the axis of spin
(outward).
• The centrifuge works using the sedimentation principle,
where the centripetal acceleration causes denser substances
and particles to move outward in the radial direction.
• At the same time, objects that are less dense are displaced
and move to the center.
• In a laboratory centrifuge that uses sample tubes, the radial
acceleration causes denser particles to settle to the bottom
of the tube, while low- density substances rise to the top.
Rate of settling of a particle,
or the rate of separation of
two immiscible liquids, is
increased many times by the
application of a centrifugal
field (force) many times that
of gravity.

Theory of Centrifugation
• From the Stokes equation five important
behaviors of particles can be explained:
• 1. The rate of particle sedimentation is
proportional to the particle size.
• 2. The sedimentation rate is proportional
to the difference in density between the
particle and the medium.
• 3. The sedimentation rate is zero when
the particle density is the same as the
medium density.
• 4. The sedimentation rate decreases as
the medium viscosity increases.
• 5. The sedimentation rate increases as
the gravitational force increases.
v = sedimentation rate or velocity
of the sphere
d = diameter of the sphere
p = particle density
L = medium density
n = viscosity of medium
g = gravitational force

Applications of Centrifugation
• To separate two miscible substances
• To analyze the hydrodynamic properties of macromolecules
• Purification of mammalian cells
• Fractionation of sub-cellular organelles (including membranes / membrane fractions)
Fractionation of membrane vesicles
• Separating chalk powder from water
• Removing fat from milk to produce skimmed milk
• Separating particles from an air-flow using cyclonic separation
• The clarification and stabilization of wine
• Separation of urine components and blood components in forensic and research
laboratories
• Aids in separation of proteins using purification techniques such as salting out, e.g.
ammonium sulfate precipitation.

5. SIZE REDUCTION
• Definition: It is a unit operation in which reduction of materials to coarse particle or
to fine powder before formulate into suitable dosage form.
• Specific Objectives
1. It increases surface area of the particle, hence increases
rate of dissolution and absorption and bioavailability,
and therefore increases therapeutic efficacy.
2. It facilitates mixing and drying by milling by increase
surface area.
3. In ophthalmic, aerosol, inhalation and parenteral
preparation where controlled particle size is required
which facilitate by size reduction.

Factors affecting size reduction
1. Hardness: Harder the material, more difficult to
reduce its size.
2. Toughness: Soft but tough material creates problem in
size reduction and its toughness is reduced by decrease
temperature.
3. Stickness: Gum and resinous substances cause problem
in size reduction.
4. Moisture content: <5% moisture suitable for dry
grinding and >50% for wet grinding.

Particle Size Separation by Different
Method

6. Mixing of Solids
• Definition
It is a unit operation in which two or more than two components in
separately or roughly mixed. So each particle lies as nearly as possible.
• Objectives
1. For homogeneity
2. To increase diffusion and dissolution
3. To facilitate dispersion
4. To ensure stability and uniformity
5. To promote chemical reaction

Mechanism of Mixing
1. For liquid mixing It requires localized mixing and general movement.
2. For powder mixing It is a neutral mixture.
• Three mechanisms may be involved:
Convective mixing (Macro mixing): It occurs by tilting material so gravitational force
causes upper layer to slip.
Diffusion mixing (Micro mixing): In this, all particles are distributed over interface.
Shear mixing: It involves thorough incorporation of material passing along forced slip
planes in a mixer.
• E.g., Ribbon mixer gives only convective mixing while Barrel mixer gives diffusion mixing.
3. Semi-solid mixing The dilatants plastic or materials are difficult to mix than Newtonian
liquids.

Homogenizer
1. Q.P Emulsifier
2. Silversion-mixer-emulsifier
3. Ultrasonic mixers

7. Extraction
• The purpose of extraction
process for crude drugs are
to obtain therapeutically
desirable portion and
eliminate the inert material
by treatment with a
selective solvent known as
menstruum.

• 2. Percolation (Exhaustive extraction)
 Process –
• Organized vegetable drug in a suitably powdered form.
• Uniform moistening of the powdered vegetable drugs
with menstruum for a period of 4 hours in a separable
vessel (Imbibition).
• Packed evenly into the percolator.
• A piece of filter paper is placed on surface followed by a
layer of clean sand so that top layers of drugs are not
disturbed.
• Sufficient menstruum is poured over the drug slowly and
evenly to saturate it, keeping the tap at bottom open for
passing of occluded gas to pass out.
• Sufficient menstruum is also added to maintain a small
layer above the drug and allowed to stand for 24 hours.
• After maceration, the outlet is opened and solvent is
percolated at a control rate with continuous addition of
fresh volume.
• 75% of the volume of the finished product is collected.
• Marc is pressed and expressed liquid is added to the
percolate giving 80% to 90% of the final volume.
• Volume is adjusted with calculated quantities of fresh
menstruum.
• Evaporation and concentration to get finished products
by applying suitable techniques and apparatus
• Small scale extraction by Percolator (Soxhlet Apparatus)
• On the laboratory scale, the apparatus consists of a flask, a
soxhlet extractor and a reflux condenser.
• The raw material is usually placed in a thimble made of
filter paper and inserted into the wide central tube of the
extractor.
• Alternatively the drug, after imbibition with the
menstruum may be packed into the extractor taking care
to see that the bottom outlet for the extract is not
blocked.
• Solvent is placed in the flask and brought to its boiling
point.
• Its vapor passes up the larger right hand tube into the
upper part of the drug and then to the condenser where it
condenses and drops back on to the drug.
• During its percolation, it extracts the soluble constituents.
• When the level of the extracts reaches the top level of
syphon tube, the whole of the percolates syphon over into
the flask.
• The process is continued until the drug is completely
extracted and the extract in the flask is then processed.
• This extraction is series of short maceration.

3. Infusion
• General Method for Preparing Infusion
• The drug is usually coarsely powdered, very fine powder
being avoided (50 gm).
• Moisten the drug in a suitable vessel, provided with a
cover, with 50 ml of cold water. Allow to stand for 15
minutes.
• Then add 900 ml of boiling water, cover the vessel tightly.
• Allow it to stand for 30 minutes.
• Then strain the mixture, pass enough water to make the
infusion measure 1000 ml
• Some drugs are supplied in accurately weighed in muslin
bags for preparing specific amounts of infusion.
• If the activity of the infusion is affected by the temperature
of boiling water, cold water should be used.
• As the fresh infusions do not keep well, they should be
made extemporaneously and in small quantities.
Infusions are dilute solutions
containing the readilysoluble
constituents of crude drugs.
Formerly, fresh infusions, prepared
by macerating the drug for a short
period in cold water or boiling
water were used.

• 4. Evaporations
• One of the quality- relevant parameter is the evaporation of the
eluate to the soft extract.
• The state of art are cautious vacuum evaporation apparatus and
evaporation temperatures not exceeding 55 0C.
• The temperature in correlation with the evaporation time is of special
importance for quality of this step of manufacture, if the extract
contains easily volatile or thermo- labile constituents.

Factors Affecting Choice of Extraction
Process
• The final choice of the process to be used for the extraction
of a drug will depend on a number of factors, including:
• 1. Character of Drug
• 2. Therapeutic Value of the Drug
• 3. Stability of Drug
• 4. Cost of Drug
• 5. Solvent
• 6. Concentration of Product
• 7. Recovery of Solvent from the Marc

8. DISTILLATION
• It is defined as the separation of the components of the liquid mixture by
process involving vaporization and subsequent condensation at another
place.
• Raoult’s law
• It states that partial vapour pressure of each volatile constituent is equal to
the vapour pressure of the pure constituent multiplied by its mole fraction
in the solution at given temperature.
• Ideal solution obeys Raoult’s law. Raoult’s law is obeyed by only a few
solution of liquid in liquids.
• Examples are benzene, toluene, n-hexane, n-heptane, ethyl bromide, ethyl
iodide.
• Dalton’s law
• It states that the total pressure exerted by a mixture of ideal gases may be
considered as sum of the partial vapour pressure exerted by each gas, if
alone were present and occupied the total volume.

Classification of Distillation Methods
• Simple distillation(Differential type)
• It is used for preparation of distilled water and water for injection.
• Flash distillation
• It vapourizes liquid by passing feed from high pressure zone to low
pressure zone.
• It is used in petroleum ether separation.
• Fractional distillation(Rectification)
• It vapourizes liquid mixture by giving rise to mixture of constituents from
which desired one is separated in pure form.
• It based on counter-current diffusion principle.
• It is used for separation of miscible liquid like acetone and water.
• It can’t separate miscible liquid which form azeotropic mixture.

• Azeotropic distillation(constant boiling type)
• It is a method in which azeotropic mixture is broken by addition of third
substance.
• Absolute alcohol is prepared by this method.
• It is used for determination of water content in substance using toluene
(I.P-1996)
• Extractive distillation
• In this, third added to azeotropic mixture is relatively non-volatile liquid
compared to components to be separated.
• Steam distillation(Differential type)
• Steam is used for separation of high-boiling substance from non-volatile
impurities.
• Used for separation of immiscible liquids.
• Used for camphor distillation and extraction of volatile oil like clove,
eucalyptus.

• Molecular Distillation (Evaporative or short path distillation)
• It is a process in which vapour phase molecule get condensed
individually without intermolecular collisions on appled vacuum.
• Used for separation of Vitamin-A and E, steroids, free fatty acid,
triglyceride.
• It is used in the refining of fixed oil.
• Destructive distillation(Dry distillation)
• It is a method in which distillate is the decomposed product of
constituents of organic matter burnt in absence of air.
• Compression distillation
• Use for obtaining fresh water from sea-water which is pyrogen free.

9. EVAPORATION
It is simply vaporization from surface of liquid. Means the removal of liquid from
solution by boiling the liquor in suitable vessel and withdrawing vapour, leaving
concentrate liquid residue and heat supply is latent heat of vaporization.
Factors Affecting Evaporation
1. Surface area of liquid: Greater the surface exposed to
evaporation higher will be the rate of evaporation like
in film evaporator.
2. Temperature: Higher the temperature, higher will be
evaporation.
3. Agitation: It breaks scum or layer and increase rate of
evaporation.

Evaporation equipments (Evaporator)

10. CRYSTALLIZATION • Nucleation
• It is the step where the solute
molecules dispersed in the solvent
start to gather into clusters, on the
nanometer scale, that becomes stable
under the current operating
conditions.
• These stable clusters constitute the
nuclei.
• Nucleation can occur spontaneously
or induce artificially by any foreign
surface.
• Crystallization is
a chemical solid-
liquid separation
technique, in
which mass
transfer of a
solute from the
liquid solution to
a pure solid
crystalline phase
occurs.

Crystal growth
• It is the subsequent growth of the nuclei that succeed in achieving the critical
cluster size.
• It occurs through four stages:
1. Transport through or from the bulk solution to an impingement site, which is
not necessarily final site.
2. 2. Adsorption at impingement site, where precursors may shed solvent
molecules. Hence solvent must be transported back in soln.
3. 3. Diffusion of growth units of precursors from site of impingement to
growth site.
4. 4. Incorporation into lattice; for precursors, after desolvation. Thus, the
growth site may also be a source of solvent that has possibility of, again,
being adsorbed before escaping into the solution.

Theory of Crystallization
(The Miers Super Saturation
Theory)
• It is well defined curve for any defined condition
of heterogeneous nucleation can be established
in super saturation zone which is parallel to
solubility curve.

Methods to Achieve Super Saturation
1. By cooling: It is applicable when solubility depend on temperature
like inorganic salt, organic substance. At higher temperature,
solution is saturated and at lower temperature solution is
supersaturated.
2. By evaporation of solvent: It is applicable to those whose solubility
independent to temperature like NaCl.
3. By addition of third component:
I. Salting out: It is applied when solubility of substance is very high so
super saturation is difficult by method 1. and 2.
II. Precipitation
III. pH change

11. DRYING
• Definition: It is process of removal of small amount of water or any
liquids from material by application of heat.
• Psychrometry: Psychrometry is the science of studying the
thermodynamic properties of moist air and the use of these
properties to analyse conditions and processes involving moist air.
• The Dry Bulb, Wet Bulb and Dew Point temperatures are important
to determine the state of humid air. The knowledge of only two of
these values is enough to determine the state—including the content
of water vapour and the sensible and latent energy (enthalpy).

Thermodynamic Properties of Air
1. Dry bulb temperature – Tdb
• The dry bulb temperature refers basically to
the ambient air temperature. It is called “Dry
Bulb” because the air temperature is
indicated by a thermometer not affected by
the moisture of the air.
• Dry-bulb temperature–Tdb, can be measured
using a normal thermometer freely exposed
to the air but shielded from radiation and
moisture. The temperature is usually given in
degrees Celsius (oC) or degrees Fahrenheit
(oF). The SI unit is Kelvin (K). Zero Kelvin
equals to –273oC.
• The dry-bulb temperature is an indicator of
heat content and is shown along the bottom
axis of the psychrometric chart. Constant dry
bulb temperatures appear as vertical lines in
the psychrometric chart.
2. Wet bulb temperature – Twb
• The Wet Bulb temperature is the temperature
of adiabatic saturation.
• Wet Bulb temperature can be measured by
using a thermometer with thebulb wrapped
in wet muslin.
• The wet bulb temperature is always lower
than the dry bulb temperature but will be
identical with 100% relative humidity (the air
is at the saturation line).
• Combining the dry bulb and wet bulb
temperature in a psychrometric diagram or
Mollier chart, gives the state of the humid air.
• Lines of constant wet bulb temperatures run
diagonally from the upper left to the lower
right in the psychrometric chart.

• Dew point temperature
The dew point is the temperature at which water vapour starts to
condense out of the air (the temperature at which air becomes
completely saturated).
• Above this temperature, the moisture will stay in the air.
• Relative humidity (RH)
• Relative humidity (RH) is defined as the ratio of the mole
fraction of the water vapour (Xw) in a given moist air sample to
the mole fraction of water vapour in an air sample
• Specific enthalpy
• The enthalpy of moist air is defined as the sum of its internal
energy and the product of its pressure and volume. Specific
enthalpy h (kJ/kg) of moist air is defined as the total enthalpy of
the dry air and water vapour mixture per kg of moist air.

Dryer Equipments (According to its principle)
• A. Convection dryer • B. Conduction dryer

Application of Unit Operation
• Formulation and pre-formulation development
Before a drug can be manufactured at any scale, much work goes into the
actual formulation of the drug. Formulation development scientists must
evaluate a compound for uniformity, stability and many other factors. After
the evaluation phase, a solution must be developed to deliver the drug in its
required form such as solid, semi-solid, immediate or controlled release,
tablet, capsule

• Powder blending
• In the pharmaceutical industry, a wide range of excipients may be blended together to
create the final blend used to manufacture the solid dosage form. The range of materials
that may be blended (excipients, API), presents a number of variables which must be
addressed to achieve products of acceptable blend uniformity. These variables may include
the particle size distribution (including aggregates or lumps of material), particle shape
(spheres, rods, cubes, plates, and irregular), presence of moisture (or other volatile
compounds), and particle surface properties (roughness, cohesivity)

• Milling
• During the drug manufacturing process, milling is often required in order to reduce the
average particle size in a drug powder. There are a number of reasons for this, including
increasing homogeneity and dosage uniformity, increasing bioavailability, and increasing
the solubility of the drug compound.

• Granulation
• Granulation can be thought of as the opposite of milling; it is the process by which small
particles are bound together to form larger particles, called granules. Granulation is used
for several reasons. Granulation prevents the "de-mixing" of components in the mixture, by
creating a granule which contains all of the components in their required proportions,
improves flow characteristics of powders (because small particles do not flow well), and
improves compaction properties for tablet formation.

• Hot melt extrusion
• Hot melt extrusion is utilized in pharmaceutical solid oral dose processing to enable
delivery of drugs with poor solubility and bioavailability. Hot melt extrusion has been
shown to molecularly disperse poorly soluble drugs in a polymer carrier increasing
dissolution rates and bioavailability. The process involves the application of heat, pressure
and agitation to mix materials together and 'extrude' them through a die. Twin-screw high
shear extruders blend materials and simultaneously break up particles. The resulting
particles can be blended and compressed into tablets or filled into capsules.

UNIT OPERATIONS : PHARMACEUTICAL ENGINEERING ON BASICS AND APPLICATION

UNIT OPERATIONS : PHARMACEUTICAL ENGINEERING ON BASICS AND APPLICATION

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