Paul Ashall, 2008
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
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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).
Paul Ashall, 2008
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.
Paul Ashall, 2008
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
e.g. ibuprofen
Bulk chemical
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 consumption (kg/kg)
high low
Energy consumption (kJ/kg)
high low
uses specific diverse
Value added high low
Molecular complexity
high low
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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’)• Ethanoletc
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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 productsetc
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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 equipmentChemical reaction reactorDistillation distillation
columnFiltration filter unitsDrying dryers (various
types)Fluid transport pipes, valves, pumps etcProcess control measurement devices, controllers, control valves etcEvaporation evaporatorsCentrifugation centrifugesHeat transfer heat exchangersGranulation granulatoretc
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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 plant services)• Steam
• 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 conditionsetc
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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
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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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ExerciseChoose 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-VCHSurvey of Industrial Chemistry, P. J. Chenier, 2002
Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.