An Introduction to

Pharmaceutical & Chemical

Process Technology

Paul Ashall

Paul Ashall, 2008

 Aspects of Industrial Chemical
Processes
• Products
• Types of process
• Flowsheets
• Mass balances
• Energy balances
• Heat transfer and heat exchangers
• Reactor design and operation
• Separation and purification processes
Paul Ashall, 2008
 Aspects of chemical processes
cont.
• Process instrumentation and process control
• Materials handling
• Process economics
• Safety and environmental issues
• Quality
etc

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 Industrial Chemical Processes
Chemical processes are used to produce chemical
products and are by definition processes which
include chemical transformation(s).
Specific products produced by the chemical and
pharmaceutical industry include: aspirin,
ibuprofen, paracetamol, naproxen, labetalol, etc
These active pharmaceutical ingredients (APIs) are
produced by chemical reactions involving organic
chemicals (organic chemistry).
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 Chemical processes cont.
• Route (materials, steps, operations etc)
• ‘Recipe’(materials, quantities, steps)
• Plant equipment (operations)
• Process operating conditions

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Many chemicals are mixed with other
chemicals to produce formulations suitable
for consumer use. These include consumer
products such as paints, fragrances,
pesticides and medicinal products. For
example ibuprofen is the active
pharmaceutical ingredient (API) in the OTC
product ‘Nurofen’, which contains other
ingredients called excipients.
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Specific processes have been developed to
produce specific chemicals. Particularly
well established processes are given names.
For example the process used to
manufacture sulphuric acid is called the
‘Contact’ process.
In some cases a chemical may be produced by
more than one process.
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The chemical industry consists of many different
sectors (or product groups), each with their own
characteristics. For example pharmaceuticals,
pesticides, fertilisers, petrochemicals, dyestuffs etc
The type of chemical produced will determine the
particular characteristics of the process (or
processes) used to produce the product. For
example compare the processes used to
manufacture ammonia and aspirin.
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 Classification of chemical products

• Bulk chemicals e.g. sulphuric acid

• Fine chemicals e.g. ‘ibuprofen’
• Speciality chemicals e.g. adhesives
• Inorganic/organic

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 continued
Bulk chemicals are characterised by a combination of two
parameters – large volume production, which is supported
by market demand, and lower unit costs, where the
principle of economy of scale is important.
Fine chemicals are produced on a relatively smaller scale in
more versatile (less dedicated generally) production units
using batch operations. Product specifications may be
more exacting and unit cost is relatively higher. Fine
chemicals may be used as ingredients in formulations or as
intermediates in the production of more complex
chemicals. For example bulk pharmaceuticals.

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Characteristics of fine versus
bulk chemicals
characteristic Fine chemical Bulk chemical
e.g. ibuprofen e.g sulphuric
acid
scale small large

price 22 $/kg 0.08 $/kg

Process type batch continuous

synthesis Multi-step Few steps

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Raw material high low
consumption
(kg/kg)
Energy high low
consumption
(kJ/kg)
uses specific diverse

Value added high low

Molecular high low

complexity
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 Speciality chemicals
These are chemically formulated products
manufactured from basic chemicals which
are used by industry and domestic
consumers for specific purposes. For
example: coatings, adhesives,
pharmaceutical products, pesticides,
cosmetics, disinfectants etc

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Chemical & pharmaceutical
companies

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 Integration of the chemical
industry with manufacturing
industry in general

For example the manufacture of polyester

textiles.
crude oil naphtha terephthalic acid/ethylene glycol PET
polyester fibres textiles
Discuss production of ibuprofen.
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 Choice of process
Examples include:
• Ibuprofen (Boots route and Hoechst-Celanese route)
• Acetic acid
• Adipic acid
• Ethylene oxide
• Vinyl chloride (ethyne and ethene based routes)
• Titanium dioxide (‘sulphate process’, ‘chloride process’)
• Ethanol
etc

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•
General factors to be considered
Yield, conversion, selectivity/mass balances
• Energy usage/energy balances
• Kinetics/rates and productivity (kg/hr)
• Number of synthetic reaction steps/reaction chemistry
• Scale of operation
• Manufacturing costs
• Separations required
• Operating conditions
• Environmental factors – waste, environmental impact, emissions, effluent, solid
waste, hazardous waste
• Health and safety factors – process safety/operating conditions, use of hazardous
materials
• Material availability
• Quality issues
• By products and co products
etc

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Process obsolescence - case study
• Routes to ibuprofen (see EP0284310A1)

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 Product obsolescence
• Sulphonamide drugs

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 Choice of route
Case study: 3, 3-dimethylindoline

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 System model of a chemical
process
Inputs: reactants, solvents, catalysts, energy
etc
Outputs: product, by-products, co-products,
spent catalyst, solvents, waste, energy etc

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Chemical process operations are of two basic
types:
• Batch processes, which operate according
to batch cycles,
• Continuous processes, which operate
continuously under steady conditions.

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 Chemical processes
Chemical processes consist of a number of
sequential and integrated operations carried out in
appropriate equipment.
For example chemical reaction carried out in a
chemical reactor.
The precise operations, sequence of operations and
equipment specifications depend on the nature of
the process, operating conditions, materials used
and product produced.
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 Chemical processes
Operation equipment
Chemical reaction reactor
Distillation distillation column
Filtration filter units
Drying dryers (various types)
Fluid transport pipes, valves, pumps etc
Process control measurement devices, controllers, control valves etc
Evaporation evaporators
Centrifugation centrifuges
Heat transfer heat exchangers
Granulation granulator
etc

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 Multi-purpose /product plant for
bulk active pharmaceutical
ingredients
• Batch reactors (stainless steel, agitator, glass-lined,
reflux condenser, jacket etc)
• Material feed system to reactors
• Separation and purification equipment ( crystallisers,
filtration, centrifuges, dryers, distillation unit etc)
• Material storage
• Process support services/Utilities (incl. heat transfer
fluids)
• Waste treatment
• Emissions control
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 Equipment
• Batch reactors
• Filter driers e.g Cogeim Nutsche
• Crystallisers
• Double cone vacuum driers
• Mixers and granulators
• Fluid bed driers
• centrifuges
• etc
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 Separation and purification
processes
Why do we need separation and purification
processes in the production of chemicals?

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 Separation processes
A typical sequence of separation processes
used in the production of bulk
pharmaceutical products is: crystallisation
(from mother liquour), filtration or
centrifugation and drying.

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 Separation processes
Factors to be considered in choosing separation/purification
process(es):
• Quantity of material to be separated
• Rate of separation required
• Feasibility
• Selectivity
• Economics
• Quality
• Equipment
• Mode of operation
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 Process support services/Utilities (or
• Steam plant services)
• Cooling water
• Chilled water
• Other heat transfer fluids
• Inert gases
• Compressed air
• Electricity
• Demineralised water/deionised water
• UP water
• Distilled water
• Effluent treatment
• etc
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 Purified Water/WFI
• Obtained from potable water
• Specified in pharmacopoeias
• Storage
• Depth filter
• Organic trap
• Carbon filter
• DI
• Filtration (0.45 micron)/UV (254 nm)
• UF (0.22 micron)
• Distillation/RO
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 WFI distribution
• Sealed storage
• Ring main (loop) circulation under
turbulent flow conditions at 85 deg cent
• No ‘dead legs’ in pipe distribution system
• UV irradiation

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 Material storage
• Reactants
• Products
• intermediates
• Solvents
• Catalysts
• reagents
• etc
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 Flowsheets
Flowsheets are used to describe the operating
details of chemical processes. There are a
number of basic types:
Flowcharts (or block diagrams),
Process flowsheets (or Process Flow
Diagram),
Piping and Instrumentation Diagrams (PID).
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 Flowsheets
• Schematic representations
• Arrangement of equipment
• Interconnections
• Movement of material
• Stream connections
• Stream flows/quantities
• Stream compositions
• Operating conditions
etc
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 Flowcharts
Simple flowcharts can be used to show the
main material routes through the process
(lines and arrows) and to depict the main
operations (blocks).

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 Process flowsheet
• Symbols
• Stream information
• Layout

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 P and I Diagram
• Equipment details and arrangement (item no.,
name, dimensions, materials of construction, rate
or capacity, occupation time, T, P, materials
handled, heat duty, power)
• Pipe details
• Valves
• Ancillary fittings
• Pumps
• Instrumentation and control loops
• Services (utilities)
• Symbols
• Layout Paul Ashall, 2008
 For a large chemical plant a large number of
such flowsheets will be required to specify
the process. These will be grouped into
individual plant operating areas.

Refer to examples
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 Exercise
Construct a process flowsheet for a batch
esterification reaction from the information
given.

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 Exercise
Construct a process flowsheet for a batch
process to produce aspirin from the
information given.

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 Exercise
Choose a chemical product and from the information
sources given below write a process description and
draw a block flow diagram of the reaction and
separation steps.
Examples: aspirin, penicillin, paracetamol.

Chemical Process Industries, R. N. Shreve and J. A. Brink, 4th ed., McGraw-

Hill.
Ullmans Encyclopedia of Industrial Chemistry, 6th ed., Wiley-VCH
Survey of Industrial Chemistry, P. J. Chenier, 2002
Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.

Paul Ashall, 2008