An Introduction to Pharmaceutical Chemical Process Technology Paul
- Slides: 42
An Introduction to Pharmaceutical & Chemical Process Technology 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 Paul Ashall, 2008
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 Paul Ashall, 2008
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. Paul Ashall, 2008
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. Paul Ashall, 2008
Classification of chemical products • • Bulk chemicals e. g. sulphuric acid Fine chemicals e. g. ‘ibuprofen’ Speciality chemicals e. g. adhesives Inorganic/organic Paul Ashall, 2008
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. Paul Ashall, 2008
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 Paul Ashall, 2008
Raw material consumption (kg/kg) high low Energy consumption (k. J/kg) high low uses specific diverse Value added high low Molecular complexity high low Paul Ashall, 2008
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 Paul Ashall, 2008
Chemical & pharmaceutical companies Paul Ashall, 2008
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. Paul Ashall, 2008
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 Paul Ashall, 2008
• • • General factors to be considered • • etc 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 Paul Ashall, 2008
Process obsolescence - case study • Routes to ibuprofen (see EP 0284310 A 1) Paul Ashall, 2008
Product obsolescence • Sulphonamide drugs Paul Ashall, 2008
Choice of route Case study: 3, 3 -dimethylindoline Paul Ashall, 2008
System model of a chemical process Inputs: reactants, solvents, catalysts, energy etc Outputs: product, by-products, co-products, spent catalyst, solvents, waste, energy etc Paul Ashall, 2008
Chemical process operations are of two basic types: • Batch processes, which operate according to batch cycles, • Continuous processes, which operate continuously under steady conditions. Paul Ashall, 2008
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. Paul Ashall, 2008
Chemical processes Operation Chemical reaction Distillation Filtration Drying Fluid transport Process control Evaporation Centrifugation Heat transfer Granulation etc equipment reactor distillation column filter units dryers (various types) pipes, valves, pumps etc measurement devices, controllers, control valves etc evaporators centrifuges heat exchangers granulator Paul Ashall, 2008
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 Paul Ashall, 2008 • Emissions control
Equipment • • Batch reactors Filter driers e. g Cogeim Nutsche Crystallisers Double cone vacuum driers Mixers and granulators Fluid bed driers centrifuges etc Paul Ashall, 2008
Separation and purification processes Why do we need separation and purification processes in the production of chemicals? Paul Ashall, 2008
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. Paul Ashall, 2008
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 Paul Ashall, 2008
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 Paul Ashall, 2008
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 Paul Ashall, 2008
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 Paul Ashall, 2008
Material storage • • Reactants Products intermediates Solvents Catalysts reagents etc Paul Ashall, 2008
Flowsheets are used to describe the operating details of chemical processes. There a number of basic types: Flowcharts (or block diagrams), Process flowsheets (or Process Flow Diagram), Piping and Instrumentation Diagrams (PID). Paul Ashall, 2008
Flowsheets • Schematic representations • Arrangement of equipment • Interconnections • Movement of material • Stream connections • Stream flows/quantities • Stream compositions • Operating conditions etc Paul Ashall, 2008
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). Paul Ashall, 2008
Process flowsheet • Symbols • Stream information • Layout Paul Ashall, 2008
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 Paul Ashall, 2008 • 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 Paul Ashall, 2008
Exercise Construct a process flowsheet for a batch esterification reaction from the information given. Paul Ashall, 2008
Exercise Construct a process flowsheet for a batch process to produce aspirin from the information given. Paul Ashall, 2008
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. , Mc. Graw-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. Paul Ashall, 2008
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