Tài liệu Pharmaceutical Coating Technology (Part 10) pdf

Page 249 10 Automation of coating processes Graham C.Cole SUMMARY Current Good Manufacturing Practice (cGMP) and the demands of the regulatory authorities world- wide requires greater care in the design of manufacturing facilities, the selection of materials used in their construction, their layout, the equipment used in the preparation of tablets to be coated and the coating operation. It is claimed that robotic systems will eventually take over all processing tasks! (Kanig & Rudic, 1986). This chapter will discuss automation concepts and suggestions based on cGMP (DHSS, 1983) in two areas: An examination of Fig. 7.1 (Chapter 7) shows the general requirement, and this chapter will describe how automation of this process can be achieved. 10.1 INTRODUCTION Since 1970 the explosion in the development of the microprocessor, the programmable controller and personal computers has provided tools to make substantial productivity improvements in manufacturing systems. Many of the major pharmaceutical products in the oral solid dosage field are now produced using automated plants. Merck’s ALDOMET manufacturing facility is well known and a well- documented example (Lumsden, 1982; Fig 10.1 ). This process uses fluidized bed coating columns. Figs 10.2 and 10.3 show schemes that uses both side - vented and conventional pans. • the design and layout of the building • the control and transfer of materials between the various unit operations. Page 250 Fig. 10.1 ALDOMET manufacturing and coating process (MSD). Fig. 10.2 Feed system to automated side-vented coating pan. (In Figs 10.2 and 10.3 —IBC: Intermediate Bulk Container; AHU: Air Handling Unit; PMCS: Process Monitoring Control System; ELECT: Electricity; ph: Phase; C/A: Compressed Air; DCE: Dust Control Equipment). The purpose here is to consider some of the ideas for automated coating systems that are incorporated into these plants, and to look at what has been achieved with products that are not produced in large volumes and, therefore, require a more Page 251 Fig. 10.3 Automated feed system to standard coating pan. flexible approach. The key driving forces towards providing better utilization of assets are: It has been suggested that, in any productivity increase over the next decade, almost 60% will be provided by new and existing technology, 25% will be provided by capital and 13% by labour management (Morley, 1984). All of these pressures are dependent on control. It is the control of the process, inventory, information flow, materials handling and the utilization of plant which is the essential part of automation. Generally, to do this efficiently requires the use of a microprocessor or computer. Depending on the complexity of the operation, the number of parameters to be recorded and the degree of control required, there are a number of systems that can be used. • the rising cost of labour relative to productivity increases • the high cost of energy and raw materials • poor material - handling facilities • the high cost of quality control • inefficient use of manufacturing equipment • short runs and a variable product mix. Page 252 10.2 SYSTEMS For the application of computer control to the coating process, some of the possible alternatives available are highlighted here. There are three main possibilities: Each system is briefly described with points to consider when evaluating each of them and finally suggestions and conclusions on the final choice. It is not an exhaustive list but more a discussion to assist in making the basic decisions. 10.2.1 Data acquisition system Fig. 10.4 shows the layout of a data acquisition system. These are normally small devices for low levels of inputs only, but some have limited computing power. They can also be used to provide printouts of the information gathered, similar to that described in Chapter 6 . They do not provide any plant control and have only limited processing of information capacity. Some can be linked to high-powered computers which would store data or manipulate it, depending on the degree of automation required. The field inputs have to be cabled back to a control location such as a control room and the system interface requires safety protection. Advantages: Disadvantages: Fig. 10.4 Data acquisition system. 1. A data acquisition system; 2. A distributed control system; 3. A centralized computer system. • Small and cheap. • No control provided. • Limited data processing. Page 253 10.1.2 Distributed control system Fig. 10.5 illustrates the layout of a distributed control system. In a distributed system not only are the hardware items geographically distributed, but the functions of processing, power and software are also distributed. Fig. 10.5 Distributed control system. • Limited number of inputs. • No data storage. • Long lengths of field cabling required. • No local operator interface. Page 254 Each hardware item performs a specific task and information is passed between the various hardware items using a dual data highway. This dual highway provides good security for communications. The field devices, such as the input, output and control devices, must be protected by suitable housing and safety equipment for use in a hazardous area, particularly if flammable solvents are used in the coating process. Computer type functions are distributed throughout the process area using smaller microprocessor devices. It can support local operator control devices located in the plant area providing these are adequately protected. This system can provide process control for continuous variables such as atomizing air pressure and tablet-bed temperature and batch or sequence control. It can be linked to other devices such as an existing in-house computer. Advantages: Disadvantages: 10.2.3 Centralized control system Fig. 10.6 shows the layout of a centralized computer control system. This is very similar to the distributed control system. It can perform all the same functions, but they are centralized within a computer system. The computer would normally be the process control manufacturer’s standard. Advantages: Disadvantages: • Batch, sequence operations and continuous control is available. • Data logging and data storage are available. • Calculations on the stored data can be performed. • Logs and reports can be generated. • Local operator interfaces can be provided. • Batch and sequence control can store and use many different recipes and values, and the system can be used to optimize process control. • System is easily expandable and very flexible. • Short field cable lengths. • High security of control as all functions are distributed. • System more suitable for plants with greater than 500 loops. • High cost due to its large capacity. • Local plant equipment must be protected in safe enclosures. • Same as distributed system. • System size tends to be intermediate between the systems illustrated in Figs 10.4 and 10.5 . • Long lengths of field cabling required. • System operation dependent on one device (the computer) thus a redundancy of a back-up computer may be required to increase reliability. Page 255 Fig. 10.6 Centralized computer system. Ideally the type of system required for a coating plant should have the following capability: • Data logging and process control of various parameters, temperature; spray rates. • Batch control is required with various recipes and sequences. • Optimization of batch control parameters. • Flexibility to change the process, size of batches, product, etc. • Local operator interface in hazardous area. • Interface to field devices suitably protected against hazardous area (intrinsically safe circuits, etc.) • Operator control/display within the control room via VDU/keyboard/printer devices. • Calculations and optimization of sampled and/or measured variables for analysis. Page 256 Either the centralized or the distributed control system would be suitable for a film-coating facility, depending on the number of coating pans which, in turn, is related to the number of variables to be measured or recorded. A number of additional options are also possible: In general, however, the centralized system is preferable to the distributed system for the following reasons: A typical centralized control room is shown in Fig. 10.7 . Most process control and data logging manufacturers use their own computers and their software structure may not be comparable with the in- house computer software. However, the necessary interface can be provided, but this is always difficult and should be avoided if possible. 10.3 INSTRUMENTATION Examples of the instruments necessary for automation were examined in Chapter 6. Here the instrumentation will not only control the process but will assist in moving materials from one unit operation to the next. A further example is shown in Fig. 10.8 . 10.4 FACILITY DESIGN AND EQUIPMENT REQUIREMENTS There are many different types of tablets that can be coated, ranging from a cosmetically coated tablet to those that use the osmotic pump principle to release the drug. Examples were illustrated in Fig. 7.3 (Chapter 7). In the development and implementation of any automated tablet-coating process there are a number of objectives that must be addressed: • Printouts and logs required. • System size relatively small (150 loops approximately). • A dual processor computer to provide back - up security for control and data storage. • Links to an in-house computer can be accommodated if a separate system is used. This data can be passed to the in - house system for processing or display if required. • Inventory control could be added. • In a potentially hazardous plant, it may be worth considering a separate emergency shutdown system for increased safety. • It is smaller and cheaper. • System input/output interface is simpler while the distributed system requires special housings. • It allows the possibility to use an existing computer. 1. What types of product are to be handled? (a) Are they highly potent? Page 257 Fig. 10.7 Centralized control room. Current Good Manufacturing Practice suggests there are two overriding considerations that take precedence. These are: A five-year forecast of requirements will be needed as there may be new coated-tablet products coming through from Research and Development and some older products may be declining in volume. These factors should be assessed in the design (b) Can they cause allergic reactions in the operators? (c) Are they mutagenic? (i) total containment of the product within a closed system; (ii) providing a barrier between the product and the operator, i.e. total protection. 2. Are these products beta- lactams, e.g. penicillin? If this is the case, then a separate manufacturing facility must be designed. 3. What quantities and mix of products are required? There may be relatively small quantities of a number of products required rather than large quantities of individual products. In one case, flexibility of the operation is the main objective requiring a multiplexity of services, whereas a single dedicated production line can save on materials handling, personnel, and special conditions (protection from light and oxygen). Page 258 Fig. 10.8 Schematic of an instrumented and computer-controlled coating pan. of a facility, the refurbishment of an existing operation or in selection of new equipment for development and production purposes. 10.5 PROCESS CONCEPT To design the facility requires an understanding of the overall tablet-coating process. The building and building services provide the envelope around the process and the process operation must be performed in areas designed to conform to cGMP. It will also need a validation programme. For any tablet-coating operation there are four essential requirements: A flow diagram should be developed, as shown in Fig. 11.2 . (Chapter 11). All or some of these operations take place whether in a laboratory or on a production scale. For efficient and accurate operations the following stages must be assessed: 1. a supply of tablet cores; 2. a supply of coating materials; 3. the process equipment; 4. a building to house the equipment, raw materials and finished product. [...]... raw Page 260 Fig 10.9 Flow diagram for storage of materials Page 261 Fig 10.10 Schematic diagram for an automated pharmaceutical dispensary materials to the production area for preparation of the powder mix ready for tablet core manufacture and raw materials for the preparation of the coating The layout of the process area will depend on the material-handling concept If pneumatic transfer is used for... Health and Social Security Kanig, J.L & Rudic, E.M (1986) The basics of robotic systems, Pharm Tech June Lumsden, B (1982) Industrial Powder Technology Conf., London, 24–25 November Morley, R.E (1984) The rate of control in automation trends and perspectives Pharmaceutical Engineering, Jan–Feb ... product to the operator and the environment 10.5.4 Layout and design of facility A typical layout is shown in Fig 10.12 Process areas require high-quality finishes to maintain cGMP standards Traditionally pharmaceutical secondary manufacturing facilities have been designed on the basis of single rooms or cubicles for each stage of the manufacturing process Transfer of materials has been accomplished using... 10.16) An alternative process based on fluid bed granulation is shown in Fig 10.18 This was built by SmithKline French (now part of SmithKline Beecham) Page 263 Fig 10.12 Typical layout for a tablet -coating process Fig 10.13 Detailed section through an automated manufacturing facility Page 264 Fig 10.14 Detailed section (contained equipment) through an automated manufacturing facility Fig 10.15 Section... the blender/granulator/dryer/mill and the blender to the tablet machine or an intermediate bulk container (IBC; see Fig 10.11) Figs 10.2 and 10.3 show an automated feed and receiving system for tablet -coating equipment Units are linked to a process monitoring and control system (PMCS) For an automated system, coated tablets can be stored in an IBC until released to packaging; the IBC can be positioned . 250 Fig. 10.1 ALDOMET manufacturing and coating process (MSD). Fig. 10.2 Feed system to automated side-vented coating pan. (In Figs 10.2 and 10.3 —IBC:. distributed control system would be suitable for a film -coating facility, depending on the number of coating pans which, in turn, is related to the number