Unit Process and Unit Operation in

Pharmaceutical Chemistry
• Considerations of a chemical process designing
• Efficiency of process and equipment
• Safety with respect to the process, raw
chemicals, finished products
• Long term effect on environment
• Financial viability of the products as demanded
by the purchaser
 Process safety
• The safe design and operation of facilities is of paramount importance to every pharmaceuticals
company. Process safety focuses on the prevention of dangerous situations, such as fires,
explosions, and the release of chemicals.
• The American Institute of Chemical Engineers emphasizes a culture of process safety through
four pillars (American Institute of Chemical Engineers, 2015):
• 1. Commitment to Process Safety: a workforce that is actively involved and an organization that
fully supports process safety as a core value will tend to do the right things in the right way at
the right time – even when no one else is looking
• 2. Understanding Hazard and Risk: the foundation of a risk-based approach which will allow
an organization to use this information to allocate limited resources in the most effective
manner
• 3. Manage Risk: the ongoing execution of risk based process safety tasks. Risk management can
help a company to better deal with the resultant risks and sustain long-term accident free and
profitable operations
• 4. Learn from Experience: Metrics provide direct feedback on the workings of RBPS systems,
and leading indicators provide early warning signals of ineffective process safety results.
Organizations must use their mistakes and those of others as motivation for action and view as
Process safety
 Process safety
• Safety and loss prevention can be expressed in "layers" of plant safety in terms of design
and implementation.Each higher layer can be activated if a lower level fails. This creates
a system with subsequent levels of safety to help prevent catastrophe from occurring.
This diagram shows the important of safety in process design. If a process is designed to
be inherently safe, additional safety "controls" will be less important and a chemical
plant will be overall safer. The goal of safety is not to reach the top of the triangle, but to
stay as close to the bottom as possible. This shows the importance of inherently safe
design and safety legislation and regulations to provide guidelines for safety and health
concerns. Regulations provide a baseline for engineers to operate when designing a
chemical plant. They have brought safety to the forefront of design, when engineers
have the maximum degree of freedom for implementation, and are no longer
considered to be an afterthought or strictly a controls issue. Plants can be designed to be
safe without the extensive use of future adaptation, safety controls, or emergency
response. Although you can never eliminate these upper layers of process safety, by
designing a process smartly and safely, engineers can reduce the consequences of
"walking up" the process safety ladder or triangle.
Design of a typical pharmaceutical process
Chemical engineering unit operations consist of five classes:
• Fluid flow processes, including fluids transportation, filtration, and solids fluization.
• Heat transfer processes, including evaporation and heat exchange.
• Mass transfer processes, including gas absorption, distillation, extraction, adsorption,
and drying.
• Thermodynamic processes, including gas liquefaction, and refrigeration.
• Mechanical processes, including solids transportation, crushing and pulverization,
and screening and sieving.
Chemical engineering unit operations also fall in the following categories which involve
elements from more than one class:
• Combination (mixing)
• Separation (distillation, crystallization)
• Reaction (chemical reaction)
 Drying process
Drying is the process of removal of water or other liquids from
material with the help of heat. The final product after drying is dry
solid or powder.
Pharmaceutical application of drying:
• To prepare granules for tablets & capsules.
• To prepare dried aluminum hydroxide, lactose & powder extracts.
• To reduce the bulk density & weight.
• For easy transport & storage.
• To facilitate grinding of crude drugs.
• To improve the stability & prevent deterioration of the drugs.
 Factors affecting drying
• The critical factor in drying operations is the vapor
- carrying capacity of the air, nitrogen, or other gas
stream passing over the drying material
• The vapor - carrying capacity determines both rate
and extent of drying
• Heat sensitivity of the product
• Physical characteristics of the product
• Nature of solvent to be removed
 Types of Dryers:
1. Dryers for damp solids
• a. Tray Dryer
• b. FBD (Fluidized Bed Dryer)
• c. Tunnel Dryer
• d. Rotatory Dryer
• e. Vacuum Dryer
Specialized drying Method
• Freeze drying
2. Dryers for slurries or solutions
• a. Drum Dryer
• b. Spray Dryer
 Tray Dryer
• Tray dryer consists of a cabinet filled
with trays & heaters are placed on
the wall of dryer.
• Tray dryers are made up of stainless
steel & heated air is circulated
throughout the trays by fans.
• Number of trays are present in the
dryer where substance to be dried
are placed over large area.
• It is very effective & popular method
of drying.
• Tray Dryer
• Air flows in the direction of the arrows over each shelf in turn

• The wet material is spread on shallow trays resting as the shelves

• The required latent heat of evaporation is

transferred convectively from the air

• Slow heat transfer => slow rate of drying

 FBD (Fluidized Bed Dryer)
• Fluidized bed dryer consists of removable bowl at the bottom of the
dryer for loading & unloading of the wet granules or other material
to be dried.
• Hot air is passed at high pressure through bottom of the bowl
which suspends granules in the air (fluidized state) & dries them.
• The temperature of the hot air and exit air are monitored & filter
bags are placed above the drying bowl for the recovery of the fines.
• It is made up of stainless steel since it directly comes in contact with
the product.
• There are vertical fluidized bed dryers and horizontal fluidized bed
dryers.
PHARMACEUTICAL
APPLICATIONS:
•It is used for the drying of the
granules in the production of
the tablets.
•Useful for mixing, granulation
and drying.
ADVANTAGES
1) It takes less time to complete drying (20-40 mins)
2) Handling time is also short.
3) Drying capacity ranges from 5 to 200 kg per hour.
4) The drying containers are mobile, easy to handle and low labour costs.
5) The thermal efficiency is higher than the tray dryer.
6) It is also used for mixing & its mixing efficiency is high.
• 7) Higher drying temperatures can be used that are not possible in tray dryer.
• 8) It facilitates the drying of thermolabile substances since the contact time for the drying is short.
DISADVANTAGES
1) Many organic powders develops electrostatic charges during drying.
2) The turbulence of the fluidized state of granules may causes attrition of some materials resulting
in the production of fine powders.
 Size Reduction
• It is the mechanical process of reducing the particle size of a
substance to smaller pieces, to coarse particles, or to powder
• Various terms have been used synonymously with size reduction
depending on the product, the equipment, and the process
• Crushing , Grinding, Milling, Pulverization and Dispersion
• particle size affects a number of characteristics in the
manufacturing process
• controlling the particle size helps assure that the milled material
will be consistent and repeatable
 Factors affecting size reduction
• Hardness -Hard materials are difficult to comminute
• Toughness -It is often more important than hardness, so that a soft but tough
material may present more problems in size reduction than a hard but brittle
substance. Ex. - Rubber - Fibrous drugs. Rubber are capable of absorbing large
amount of energy through elastic and plastic deformation. Such materials can be
milled by cooling
• Stickiness It may cause difficulty in size reduction, since a material acts as a lubricant
& lowers efficiency of the grinding surfaces. Example:- Grinding of gummy or
resinous
• Softening Temperature -The heat during size reduction processes softens and melts
materials with a low melting point. Ex. – Synthetic gums and resins - Heat-sensitive
drugs may be degraded or even charred
• Moisture content -An increase in moisture can decrease the rate of size reduction to a
specified product size. The presence of more than 5% water hinder comminution and
often produces a sticky mass upon milling. Only a small amount of energy put into a
milling operation actually effect size reduction (2%)
 Methods for size reduction
There are four main methods of effecting size reduction
• Cutting:- the material is cut by means of a sharp blade or
blades
• Compression:- the material is crushed by application of
pressure
• Impact:- material is hit by an object moving at a high speed or
it strikes a stationary surface and the material is broken down
into small places
• Attrition:- the pressure is applied to the material as in the case
of compression, but the surfaces are in motion relative to each
other.
 Milling
Milling is the mechanical process of reducing the particle size of a
substance powder.

• Particle size affects a number of characteristics in the manufacturing process

• Controlling the particle size helps assure that the milled material will
be consistent and repeatable
• Improve material blending and prevent segregation
• Increase the material’s surface area to improve a material’s solubility
• To facilitate drying of wet masses.
• Ball mill
• Both impact and attrition methods are used.
• Consists of a hollow cylinder containing balls (30-50%) of its space.
• The amount of material in a mill is considerable important.
• Speed of ball mill has a considerable effect on grinding.

• At low speed – balls will slide or roll over each other.

• At high speed – balls will be thrown out
Advantages of ball mill
• It is capable of grinding a wide variety of materials
• It can produce very fine powders
• It is economical and simple to operate
• It can be used for batch or continuous operation
• It can be used in completely enclosed form, which makes it especially suitable
for use with toxic materials

Disadvantages
• Contamination may happen because of wearing of balls and partially from
casing.
• Soft materials may stick on the sizes of the mill.
 Filtration
• Filtration is process that involves the removal or separation of
a solid from a fluid or a fluid from another fluid
• The preparation of pharmaceutical dosage forms frequently
requires the separation of particles from a fluid
• Objectives
Sparkling liquid that is free of
• Crystalline precipitates or amorphous
• Colloidal hazes
• Insoluble liquid drops
• Removal of microbes or sterilization
 • Factors Affecting Filtration rate
• Classical theory of Darcy and Poiseuille, the basic filtration equation can be
written as

 The area available for filtration (A).

 The pressure difference across the filter bed (filler

medium and any cake formed)

 The viscosity of the fluid passing through the filter

Increase viscosity =>greater resistance for movement

 The thickness of the filter medium and any deposited

cake (L)

 Increased Cake = >decreased rate of filtration

Types of filters
• Pressure Filters
• Horizontal Pressure Filters
• Vertical Pressure Filters
• Tube Press
• Vacuum Filters
• Batch Vacuum Filters
• Continuous Vacuum Filters
• Rotary-Drum Filter
• Disc Filter
• Pan Filter
 Mixing
• It is a process in which two or more components in a
separate or roughly mixed condition are treated so
that each particle lies as nearly as possible in contact
with a particle of each of the other ingredients
Purposes of pharmaceutical mixing
• To ensure even distribution of the
• To ensure even appearance
• To ensure the release of the drug at the correct site and
at the desired rate
 Mechanisms of solid mixing
• Convective mixing -Arises when there is the transfer of relatively
large group of particles from one part of the powder bed to another
as might occur when a mixture blade or paddle moves through the
mix
• Shear mixings -When a layer of material moves / flow over another
layer
• Diffusion mixing -When the powder bed is forced to move or flow .
This is because the powder particles will become less tightly packed
and there is an increase in the voids space between them. Under this
circumstance, there is a potential for the particles to fall under
gravity through the void created. results in low rate of mixing.
Mechanisms of Mixing for Liquids
• Bulk transport -involves the movement of a relatively
large amount of materials from one position in the mix
to another. It tends to produce a large degree of
mixing fairly quickly
• Turbulent mixing -Arises from the haphazard
movement of molecules when forced to move in a
turbulent manner
• Molecular diffusion -Occurs with miscible fluid
whenever a concentration gradient exists and will
eventually produce a well mixed product
 Mixing Equipments
• Agitator.
• Ribbon Blender.
• Static Mixers.
• Emulsifiers.
• Drum Mixer.
• Tumble Blender.
 Distillation
• Distillation is a method of separating mixtures based on differences in
volatility (vapour pressure) of the components in a boiling liquid mixture
• It is a unit operation, or a physical separation process, and not a chemical
reaction.
• It is used in pharmacy either to extract volatile active principles from
vegetable drugs or to separate volatile substances from less volatile
impurities.
• Distillation apparatus comprises of three major, firstly distillation flask
which is used for heating the mixture and volatizing the components,
secondly condenser; used for cooling the vapors back to liquid state, and
lastly collection vessel.
 Types of Distillation
Distillation can be classified into four main
types
• 1. Simple distillation i. Under atmospheric
pressure ii. Under reduced pressure
• 2. Fractional distillation
• 3. Steam distillation
• 4. Destructive distillation
 Crystallization
• Crystallization refers to the formation of solid crystals from a homogeneous solution
• It is essentially a solid-liquid separation technique
• The processes by which a crystal forms are called nucleation and growth.
• Nucleation is the formation of a small mass on to which a crystal can grow.
• Growth is the addition of more solute molecules to the nucleation site
• In order for crystallization to take place a solution must be "supersaturated“
• Super saturation refers to a state in which the solvent contains more dissolved solute
• Primary nucleation is the first step in crystallization.
• The second chief mechanism in crystallization is called secondary nucleation requires
"seeds" or existing crystals to achieve crystal growth
• The four most common methods of reaching supersaturation in industrial processes
are: Cooling, Solvent Evaporation, Drowning :addition of a nonsolvent to the
solution which decreases the solubility of the solid, Chemical Reaction: alter the
dissolved solid to
Equipment Used in Crystallization.
• Tank Crystallizers. This is probably the oldest and most
basic method of crystallization.
• Scraped Surface Crystallizers.
• Forced Circulating Liquid Evaporator-Crystallizer.
• Circulating Magma Vacuum Crystallizer.