An Introduction to Pharmaceutical & Chemical Process Technology Paul Ashall
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
Aspects of chemical processes cont. Process instrumentation and process control Materials handling Process economics Safety and environmental issues Quality etc
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).
Chemical processes cont. Route (materials, steps, operations etc) Recipe (materials, quantities, steps) Plant equipment (operations) Process operating conditions
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.
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.
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.
Classification of chemical products Bulk chemicals e.g. sulphuric acid Fine chemicals e.g. ibuprofen Speciality chemicals e.g. adhesives Inorganic/organic
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.
Characteristics of fine versus bulk chemicals characteristic Fine chemical e.g. ibuprofen scale small large Bulk chemical e.g sulphuric acid price 22 $/kg 0.08 $/kg Process type batch continuous synthesis Multi-step Few steps
Raw material consumption (kg/kg) Energy consumption (kj/kg) high high low low uses specific diverse Value added high low Molecular complexity high low
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
Chemical & pharmaceutical companies
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.
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
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
Process obsolescence - case study Routes to ibuprofen (see EP0284310A1)
Product obsolescence Sulphonamide drugs
Choice of route Case study: 3, 3-dimethylindoline
System model of a chemical process Inputs: reactants, solvents, catalysts, energy etc Outputs: product, by-products, co-products, spent catalyst, solvents, waste, energy etc
Chemical process operations are of two basic types: Batch processes, which operate according to batch cycles, Continuous processes, which operate continuously under steady conditions.
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.
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
Multi-purpose /product plant for bulk active pharmaceutical ingredients Batch reactors (stainless steel, agitator, glasslined, 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
Equipment Batch reactors Filter driers e.g Cogeim Nutsche Crystallisers Double cone vacuum driers Mixers and granulators Fluid bed driers centrifuges etc
Separation and purification processes Why do we need separation and purification processes in the production of chemicals?
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.
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
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
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
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
Material storage Reactants Products intermediates Solvents Catalysts reagents etc
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).
Flowsheets Schematic representations Arrangement of equipment Interconnections Movement of material Stream connections Stream flows/quantities Stream compositions Operating conditions etc
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).
Process flowsheet Symbols Stream information Layout
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
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
Exercise Construct a process flowsheet for a batch esterification reaction from the information given.
Exercise Construct a process flowsheet for a batch process to produce aspirin from the information given.
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, 4 th ed., McGraw-Hill. Ullmans Encyclopedia of Industrial Chemistry, 6 th ed., Wiley-VCH Survey of Industrial Chemistry, P. J. Chenier, 2002 Kirk-Othmer Encyclopedia of Chemical Technology, 4 th ed.