The fundamentals of unit operations

Introduction to Pharmaceutical Engineering

What is pharmaceutical engineering?
• Pharmaceutical engineering is concerned with the study of industrial process needed to convert raw or bulk product into
value added pharmaceutical product such as drugs
• Pharmaceutical engineering focuses on designing, building, and improving optimal manufacturing facilities that produce
drugs as well as discovering and formulating medication
• Pharmaceutical engineers are involved in all aspects of pharmaceutical manufacturing. This includes designing and
operating machines, determining product presentation, designing packaging labels, and more. They can also have roles
designing, building, operating, and improving pharmaceutical manufacturing facilities.

Some Common Definitions:

1. Bulks are active drug substances used to manufacture dosage- form products,
process medicated animal feeds or compound prescription medications.
2. Drugs are substances with active pharmacological properties in humans and
animals. Drugs are compounded with other materials, such as pharmaceutical
necessities, to produce a medicinal product.
3. Excipients are inert ingredients which are combined with drug substances to
create a dosage form product. Excipients may affect the rate of absorption,
dissolution, metabolism and distribution in humans or animals
4. Biologics are bacterial and viral vaccines, antigens, antitoxins and analogous
products, serums, plasmas and other blood derivatives for therapeutically
protecting or treating humans and animals.
For manufacturing of pharmaceuticals, bulk drugs, antibiotics, biological products etc. from raw materials, number of
equipments and process are involved:
1.Production of dosage forms: APIs are converted to design various dosage forms such as tablet, capsule, emulsion, suspension and
Injections to make it suitable for patients. Eg. Conversion of paracetamol (acetaminophen) into tablet and Syrup formulations etc.
2. Production of bulk drug: Raw materials are converted to API/Bulk drug.

3. Production of biologicals: Production and extraction of different pharmacologically active products from microorganism, plants or
animals. For example: vaccine, insulin etc.

Each of these manufacturing process Laboratory scale Pilot scale Industrial scale
is developed

Different types of equipment , technology and process are used during this conversion. The study of pharmaceutical engineering is
vital to get good knowledge about design, fabrication, assembly, operation and maintenance of equipment. The knowledge of
effectivity, efficiency, validity, economy and safety of the each process is also vey essential for pharmacist.
 The fundamentals of unit operations
Unit operations
Unit operation examples:
1.Pharmaceutical industry: a. The powder raw materials API and
excipients are converted to wet mass by proper mixing to form
granules. Granules are dried to obtain free flowing dry granules which
are compressed to make tablet.
b. In herbal drug productions, plant extract is dried properly to
enhance the shelf life of the product otherwise that might
deteriorate.
 Unit process
• Unit process in which several unit operations are combined in a sequence to achieve the objective of a
chemical or physical process
• Unit process involves Principle chemical conversions leading to synthesis of various useful product

In above process four unit processes are involved such as hydroxylation, nitration,
reduction and acetylation. In each unit process a number of unit operation
Flowchart: First unit process is nitration of benzene where above unit operations are involved
Unit operations (such as
crystallization, filtration, drying and
evaporation) are used to prepare
reactants, purifying and separating
its products, recycling unspent
reactants, and controlling energy
transfer in reactors.
 Scientific foundation of Unit operations
A good knowledge on some physical and chemical laws is essential to operate and understand different unit operations.

CaCO3 Cao + co2

100g 80g + 20g
Unit operations
50g 45g + 5g

T YIELD =45/50=0.9 x 100= 90%

P YIELD= 80%, 70
Law of Conservation of Mass
According to this law, during any physical or chemical change, the total mass of the products remains equal to the total mass of
the reactants.
Another way of stating this is, "In a chemical reaction, matter is neither created nor destroyed." The law of conservation of
mass is also known as the "law of indestructibility of matter."
For example, If heating 10 grams of CaCO3 produces 4.4 g of CO2 and 5.6 g of CaO , show that these observations are in
agreement with the law of conservation of mass.
Mass of the reactants, CaCO3 : 10g Raw Materials = Products + Waste Products + Stored
Mass of the products, CO2 and CaO : 4.4g+5.6g=10g Products + Losses
• Matter may  undergo  physical  and  chemical  changes.
• In  a  physical  change,  matter  changes  shape   or  form  but  not  chemical  composition.
• A  phase  change, such  as  melting  or  boiling, indicates a   physical  change.
• In  a  chemical  change,  bonding  patterns  change  and  new  substances  form.
• All  chemical  reactions  are  chemical  changes.
• The  Law  of  Conservation  of  Matter  states  that matter  cannot  be  created  or  destroyed.
In  a   physical  change,  substances  can  change  form, but  the  total  mass  remains  the  same. In  a  chemical   change, the
 total  mass  of  the  reactants  always  equals  the  total  mass  of  the  products
Law of conservation of energy
The law of conservation of energy states that energy can
neither be created nor destroyed - only converted from one
form of energy to another. This means that a system always
has the same amount of energy, unless it's added from the
outside. This is particularly confusing in the case of non-
conservative forces, where energy is converted from
mechanical energy into thermal energy, but the overall energy
does remain the same. The only way to use energy is to
transform energy from one form to another.
a. Conversion energy from one form to other
b. Transfer of energy from one place to other place
c. Storage of energy in various form
The amount of energy in any system, then, is determined by
the following equation:

UT=UI + W+ Q

UT is the total internal energy of a system.

UI is the initial internal energy of a system.
W is the work done by or on the system.
 Fluid flow

(a) Atoms in a solid are always in close contact with neighboring atoms, held in place by forces represented here by springs. (b)
Atoms in a liquid are also in close contact but can slide over one another. Forces between the atoms strongly resist attempts to
compress the atoms. (c) Atoms in a gas move about freely and are separated by large distances. A gas must be held in a closed
container to prevent it from expanding freely and escaping.
• Generally, matter exists in many one of four fundamental states (though there are many more): solid, liquid,
gas, or plasma (although materials with intermediate properties exist, in particular, materials that exhibit both
solid-like and fluid-like properties e.g. liquid crystals)
• Fluid is considered to be a mass of substance formed by a series of layers. When attempt is made to change its
shape, the layers of fluid slide over one another until a new shape obtained.

• The substances which have the tendency to flow is also called as fluid

• Fluid (Liquid or gas) flow may be defined as the flow of substances that do not permanently resist distortion
Fluid Mechanics is the science that deals
with behavior of fluids at rest (fluid
statics) or in motion (fluid dynamics) and
the interaction of fluids with solids or
other fluids at the boundaries.

Fluid flow is an essential element of many pharmaceutical processes. The ability to propel fluids through pipes and to direct
materials from one location to another is central to the successful manufacture of many products.
 Properties of Fluid
Different Properties Of Fluids
Though each fluid is different from others in terms of composition and specific qualities, there are some properties which every
fluid shares.
These properties can be broadly categorized under:
Kinematic properties: These properties help in understanding the fluid motion. Velocity and acceleration are the kinematic
properties of the fluids.
Thermodynamic properties: These properties help in understanding the thermodynamic state of the fluid. Temperature, density,
pressure, and specific enthalpy are the thermodynamic properties of the fluids.
Physical properties: These properties help in understanding the physical state of the fluid such as colour and odour.

Density
Density of a fluid is defined as the ratio of the mass of the fluid to its volume. The density of gases is dependent on
pressure and temperature, while the density of liquid remains constant. The density of water is 1000 kg.m -3 while
density of air is 1.225 kg.m-3.
Suppose a block of brass and a block of wood have exactly the same mass. If both blocks are dropped in a tank of water, why does
the wood float and the brass sink? This occurs because the brass has a greater density than water, whereas the wood has a lower
density than water.

Water : 1

X: 0.95

Figure (a) A block of brass and a block of wood both have the same weight and mass, but the block of wood has a much
greater volume. (b) When placed in a fish tank filled with water, the cube of brass sinks and the block of wood floats. (The
block of wood is the same in both pictures; it was turned on its side to fit on the scale.)
The average density of a substance or object is defined as its mass per unit volume,
ρ =m/V
where the Greek letter ρ (rho) is the symbol for density, m is the mass, and V is the volume.
Pressure is defined as a normal force exerted by a fluid per unit area. Since pressure is defined as force per unit
area, it has the unit of newtons per square meter (N/m2), which is called a pascal (Pa). That is,

Vapour Pressure (p) – Liquids exhibit a vapour pressure, which contributes to the total pressure
above the liquid.
Viscosity (µ) – This is the fluid property responsible for resistance to applied forces. Honey
has high viscosity, water has much lower viscosity, and air has an even lower viscosity. its SI
units are pascal-second (Pa·s) or kilogram per meter per second (kg·m−1·s−1). The viscosity of
liquids decreases rapidly with an increase in temperature, and the viscosity of gases
increases with an increase in temperature.

Surface Tension (σ) – Liquids in contact with gases (e.g. water in contact with air) form an
interface. The liquid molecules at the interface are attracted to each other more than to the
gas molecules, to they tend to pull sideways
The cohesive forces between molecules in a liquid are shared with all neighboring molecules. Those on the
surface have no neighboring molecules above and, thus, exhibit stronger attractive forces upon their nearest
neighbors on and below the surface. Surface tension could be defined as the property of the surface of a liquid
that allows it to resist an external force, due to the cohesive nature of the water molecules.
Classifications of Fluid Flows
Some of the general categories of fluid flow problems are as follows;

Inviscid flow is the flow of an inviscid fluid, in which the viscosity of the fluid is equal to
zero
Major losses are associated with frictional energy loss
that is caused by the viscous effects of the medium and
roughness of the pipe wall. Minor losses, on the other
hand, are due to pipe fittings, changes in the flow
direction, and changes in the flow area
 OSBORNE REYNOLDS’ DEMONSTRATION
In nature and in laboratory experiments, flow may occur under two very different regimes: laminar
and turbulent. In laminar flows, fluid particles move in layers, sliding over each other, causing a small
energy exchange to occur between layers. Laminar flow occurs in fluids with high viscosity, moving at
slow velocity. The turbulent flow, on the other hand, is characterized by random movements and
intermixing of fluid particles, with a great exchange of energy throughout the fluid. This type of flow
occurs in fluids with low viscosity and high velocity.
The dimensionless Reynolds number is used to classify the state of flow. The Reynolds Number
Demonstration is a classic experiment, based on visualizing flow behavior by slowly and steadily
injecting dye into a pipe.
Osborne Reynolds was an Irish-born innovator in the understanding of fluid dynamics. In 1883
Reynolds demonstrated the transition to turbulent flow in a classic experiment in which he examined
the behaviour of water flow under different flow rates using a small jet of dyed water introduced into
the centre of flow in a larger pipe.

https://www.youtube.com/watch?v=xmNcHsvEDRE
https://www.youtube.com/watch?v=pae5WrmDzUU
The Reynolds number (Re) helps predict flow patterns in different fluid flow situations. The
Reynolds experiment determines the critical Reynolds number for pipe flow at which laminar
flow (Re<2000 ) becomes transitional (2000<Re<4000 ) and the transitional flow becomes
turbulent (Re>4000).

Laminar: Re= 1000 / 5 = 250<2

Turbulent : 50000 / 5 = 10000>4000

Applications of Reynolds number
 Fluids Pressure and Depth
The absolute pressure is the sum of the atmospheric pressure and the gauge pressure
PT = Pa + PF
PT = Pa + pgh
Pa

The pressure at a depth h below the surface of the liquid

is due to the weight of the liquid above it. We can
quickly calculate:

F
where
PF
W=mg =AH Ρ g p is the density of the fluid,
ρ (rho) is the symbol for density, m is the mass, and V is the volume g is the acceleration of gravity
Ρ =m/V m= V Ρ m= AH Ρ h is the height of the fluid above the object
volume=area*height V= AH A area
Pf = F/A = ρ A * H g/A = ρHg
ρ =m/V
m= pv
F=ma F= mg
=ρvg
V= A *H
=ρA*Hg
Transportation of Fluid
H2O + CH3CH2OH

100C 78C

78C
https://www.youtube.com/watch?v=kNZi12OV9Xc
A B
90A 80B
45A 45A
40B 40B
https://www.youtube.com/watch?v=jNMZbseLutI https://www.footprints-science.co.uk/index.php?quiz=Distillation
What is the difference between Leaching and Extraction?
Definition of Leaching and Extraction:
• Leaching is the process where a solid material in a mixture is separated out by dissolving it in a suitable solvent.
• In extraction, a given compound is separated from one chemical phase to another due to the polarity differences.

Chemical Principle:
• Leaching occurs via a concentration gradient for soluble components.
• Extraction is governed by the Partition theory.

Application:
• Leaching, which is simpler in approach, is commonly applied at industrial scale.
• Extraction is often used in laboratory level.

https://www.youtube.com/watch?v=7_AOw68oxOw https://www.youtube.com/watch?v=VWZvr4TIqj4
Leaching is a process to separate the components from a solid mixture by bringing that mixture
in contact with a liquid solvent in which these components are soluble. There are three
important factors that are required for leaching to occur. They are a compound mixture, a
solute, and a solvent. When a liquid or solvent is applied or brought in contact with a compound
mixture, the components which are soluble in the solvent starts to dissolve while other
components remain in a slurry. These components that dissolve are called ‘solutes.’ Therefore,
upon the application of the solvent in excess, the solutes can be removed from the initial
compound mixture. Even though it is expected only for the solutes to be present in the solvent,
it only happens under ideal conditions. Therefore, the solvent usually contains other impurities
from the slurry. Leaching is a type of ‘solid-liquid’ extraction.
Leaching method is commonly used in industries when solid materials are to be separated from a
solid mixture. Some common examples include separation of sugar from sugar beet with hot
water, separation of metal from metal ore using acid, etc. In nature, it is through leaching that
heavy metals and other soil contaminants enter the ground water ways.
What is Extraction?
Extraction is also a process to separate components from a compound mixture, but here, the
compounds in one chemical phase are being separated out to another phase. Usually extraction takes
place between two immiscible solvents, which is explicitly known as ‘solvent-solvent’ extraction. A
compound mixture can be separated into components among two immiscible solvents depending on
the affinities of the various components to each solvent used.
 Wet tablet: 100mg

Drying tablet: 90 mg

Water : 10mg
%LOD: = 10/100 =10%

Loss on Drying is an unspecific analytical technique

removing not only water but all other volatile impurities like
alcohol etc. ... The Loss on Drying Test is designed
to measure the amount of water and volatile matters in
a sample when the sample is dried under specified
conditions.