Tài liệu Pharmaceutical Coating Technology (Part 8) pptx

Page 205 8 Coating pans and coating columns Graham C.Cole SUMMARY This chapter provides some examples of the type of equipment that is currently available. It is not exhaustive, but will highlight the main features that should be considered when evaluating and selecting appropriate units together with ancillary equipment for spraying and control of the coating process. 8.1 CONVENTIONAL COATING PANS It is not proposed to discuss in detail the use of conventional coating pans as these are being phased out with the preference for more sophisticated pans and systems. Various methods have been used to improve the coating characteristics in this type of pan which was originally designed for sugar coating. Some examples are shown in Figs. 8.1 – 8.3. The modifications made to sugar-coating pans were an attempt to utilize existing equipment and while successful for solvent-based film-coating systems, they do not have the advantages of side-vented pans when aqueous film coats are applied. 8.2 MANESTY ACCELACOTA The Accelacota is used as a model against which all other manufacturers’ units are compared. That is not intended to imply any preference, but as a means of providing a road map through the maze of information available. The data quoted is intended as a guideline to indicate the range and size of the Accelacotas and the most suitable ancillary equipment available. Margins of safety Page 206 Fig. 8.1 Standard coating pan. have been included to allow for a range of operating conditions. They should not be considered as specific nor should they be compared with other manufacturers’ quoted data. Where comparisons are to be made, these should be related to the particular coating conditions. Like must be compared with like. Four sizes of Accelacota are available: The essential features are illustrated in Figure 8.4 . The Accelacota has a horizontal rotating cylindrical drum, the curved surface of which is uniformly perforated. The ends of the cylinder are conically dished, so that tablets in the drum are inverted and also mixed laterally during the coating operation. There are baffles to assist the mixing process. Drying air enters the drum through the perforations on the side remote from the tablet bed, and is drawn through the bed by the exhaust fan located in the exhaust duct connected to the plenum positioned under the tablet bed. This plenum has a mouth that fits closely to the outside of the perforated curved surface of the drum. The angles of the front and rear sides of the pan are 56° and 61° respectively, which was originally intended to ensure complete mixing of the tablets from the top of the bed to the bottom and from front to rear. However, it was found that this was insufficient to ensure homogeneous mixing and baffles were fitted. Generally, • Model 10, operates with a batch size of 8 – 18 kg. • Model 75, operates with a batch size of 40 – 90 kg. • Model 350, operates with a batch size of 250 – 450 kg. • Model 150, operates with a batch size of 80 – 180 kg. Page 207 Fig 8.2 Standard coating pan and a Pelligrini pan using the Glatt immersion - Sword system. Page 208 Fig. 8.3 Standard coating pan using the immersion tube system. Fig. 8.4 Manesty Accelacota. Page 209 the baffles are of the same shape but of different size for each model and can be easily removed or replaced with those of a different design depending on the physical characteristics of the tablet to be coated, e.g. friability. The batch size for each particular model will depend upon the bulk density of the tablets. Maximum loading will be achieved with tablets made from a high- density material or from small tablets which will have a high packing density. Exceeding these maximum loadings can cause damage to the drive mechanism. Minimum loadings are found by experience and depend on size and shape of the tablets. If the units are used with batch sizes below these levels, then it is likely that problems will be encountered due to a large portion of the baffles being exposed above the tablet bed. In addition, the exhaust plenum will not be completely covered and this can result in the drying air bypassing the tablets before entering the exhaust duct. Shape can affect the coating process in a number of ways. Tablets shaped as squares can cause sticking problems and the formation of ‘twins’. Logos across the centre of bi-convex tablets result in damage to the intagliations. It is, therefore, an aspect of tablet design which should be appreciated by both marketing and formulation departments. Small tablets produce a very dense bed in the coating pan which tends to reduce the batch size and increase the coating time. For sugar coating it should be remembered that the maximum loads refer to the weight of the coated tablets and not to the weight of the cores. Therefore, when pan loadings are optimized both the weight of the core and coated tablet need to be taken into consideration. Having decided upon a batch size, coating times can be estimated from the following: 1. Sugar coating. Approximately 6–7 h are required to double the core weight. Thicker or thinner coatings will take proportionally longer or shorter. Coating time is directly proportional to the weight of coating applied. This time is typical but very much shorter times can be obtained with certain coating formulations and favourable tablet shapes. Care must be exercised when comparing these times with those quoted by different equipment manufacturers as they may be quoting times for favourable rather than average conditions. Considerably longer may be needed to finish the coating to produce an elegant product with a high gloss. 2. Solvent-based film coating. From 30 to 90 min: 30 min is usual where a very thin transparent coating is applied (this type of coating would be used to prevent dusting rather than as a protective coat) but normal thicknesses require 45–60 mins. When coating a batch of small tablets (less than 10 mm diameter) which has a high-density bed, the time could increase to about 75 min. The longest coating time would occur when thick coatings are being applied to small tablets. 3. Aqueous -based film coating. Coating times range from 45 min to 3 h with a typical time being about 90 min. The lowest and highest times apply for a variety of reasons similar to those given for a solvent - based coating. Page 210 These times have been generalized and apply to all models. In practice, however, if a particular coating formulation is used under similar conditions in a range of different sizes, the times tend to increase slightly for the larger pans. When evaluating the suitability of a particular model for a coating process, allowances must be made for loading, unloading, cleaning and maintenance. For the Accelacota the following loading and unloading options are available The time required for each operation will depend upon the method used. The manual process can be considered the worst case. The following times are typical: The Accelascoop is available for the 75, 150 and 350 models and this attachment significantly reduces the unloading time. Further improvements in productivity can be achieved by using a conveyor rather than a container. Containers should be designed to hold multiples of the capacity of the Accelascoop. Mechanical or pneumatic loading and unloading systems can be designed to meet specific requirements. The Accelacota models 150 and 350 are available with automatic unload. This material handling option allows for the automatic discharge of tablets, through an inward-opening flap in the pan, into a product container or onto a conveyor. Automatic unload may be operated manually or linked to a control panel as part of a fully automatic coating system. This concept is illustrated in Fig. 8.5 . 8.2.1 Cleaning Two options are available, the manual method and an automatic washing system called the Auto Wash (Fig. 8.6 ). All Accelacotas are fitted with a sink below the coating drum which is used either as a unit to hold the various cleansing agents or to collect washings from a clean-in- place system. This is partially filled with water, solvent or cleansing agent and the drum rotated through this solution. Where manual systems are used, water (or solvent) can be sprayed onto the internal surface and collected in the sink and discharged into an effluent system. The clean in place (CIP) system (Auto Wash) can be fitted to both the 250 and 350 models. Designed to operate inside the pan only, or in the pan interior, cabinet, and inlet and outlet ducts, strategically positioned nozzles ensure thorough cleansing of the coating area and surrounding zone. Washing can be linked to either a manual or a fully automatic control panel to form part of the complete coating • manual; • Accelascoop; • pneumatic transfer; • automatic unload. Loading Unloading Model 10 2–3 min 5 min Model 75 4–5 min 8 min Model 150 5–6 min 10 min Model 350 10–20 min 30–40 min Page 211 Fig. 8.5 Automatic loading and unloading system. system. It should be remembered that the wash cycles need to be carefully formulated and validated. The absence of active ingredients or excipients from the rinse water is not accepted by the FDA as evidence that the equipment is clean. Swab tests will need to be taken from strategic points in the system and analysed. Coatings that are water soluble can be hosed off the inside of the pan and drained through the sink. Alternatively, the sink can be filled and the pan rotated through it to dissolve material that has adhered to the pan walls. Cleaning after a sugar-coating process can be achieved in approximately 30 min in the best case, but coatings that contain materials which cause strong adhesion to the pan will take longer. Allowing one hour for cleaning would be quite generous, but it must be remembered that cleaning is an essential part of cGMP (current Good Manufacturing Practice) and cannot be short-circuited. 8.2.2 The air flow system A typical schematic layout is shown for free standing models in Fig. 8.7, which illustrates the coating pan, hot air unit, fan unit (exhaust), damper controls and interconnecting duct work. (a) Exhaust air It is essential to have some means of drawing the air through the bed of tablets. In its simplest form this consists of an exhaust fan and ducting to carry the air from the plenum to the fan and from the fan to the atmosphere. The optimum quantity of air will vary with the evaporation rate required; the total pressure drop will depend upon the resistance to air flow of the tablet bed, the resistance of the exhaust ducting, and any additional equipment such as filters and solvent recovery system that may be fitted. It should be remembered that the exhaust air will contain a Page 212 Fig. 8.6 The Manesty Auto Wash system. percentage of particulates ranging in size from submicron to 200–300 µm and levels of solvent. Additionally conditions will not always be constant. The type of coating may change, the batch size may vary and the inlet air conditions may also vary. An oversize fan is therefore used and a damper is incorporated into the exhaust ducting to adjust the air flow for particular conditions. It is essential to have a control and instrumentation system that will modify the condition of the air as it enters the coating pan, depending on the local climatic conditions. Sugar coating For this process it is necessary to stop the air flow at various stages during coating. Page 213 Fig. 8.7 Schematic of complete air flow system. This can be achieved by closing the damper completely. Stopping the fan has been found to be an unsatisfactory means of shutting off the air flow because natural convection takes place through the ducting and this will affect the quality of the coating. The Model 10 contains an exhaust fan and damper unit built into the cabinet which requires connecting to an external exhaust duct and filter system. Models 75 and 150 incorporate a free-standing exhaust unit which contains the fan, motor, starter and the damper valve. The damper valve can be manually preset to a partially or fully open position to regulate the air flow and can be moved from the preset position to the fully closed position by a pneumatic signal. The equipment is housed in a cabinet with a sound-absorbing lining to reduce the noise of the fan. These units are suitable for standing alongside the appropriate model or mounting remotely and using interconnecting ductwork. An overrated fan is used which allows for longer lengths of ducting to be used when necessary. The required volume of air can be regulated by means of a damper valve. The Model 350 requires a much larger air volume and flow. The size of the fan and the unit housing the fan and starter would be too large and expensive to be conveniently sited alongside the Accelacota. It is essential to design a properly balanced system. The use of qualified heating, ventilating and air- conditioning engineers to achieve this is the best option. The fan and starter and a section of Page 214 ductwork containing the damper valve and assistance with the ducting layout can be obtained from Manesty for integration into the facility. To prevent atmospheric pollution a filter must be fitted in the exhaust ducting, and it may be necessary to use a more powerful fan to overcome the resistance of the filter as its efficiency is reduced during the coating process. This will affect the coating, resulting in a reduction of the rate of evaporation, a reduction in the spray rate and longer coating times. It is, therefore, advisable to fit some form of pressure drop indicator to the filter. A simple manometer with alarm can be sufficient to warn the operator that conditions are changing and that the filter requires cleaning. Alternatively, a more elaborate filter system with automatic cleaning could be employed. Alternatives to filters are discussed in Chapter 9 . (b) Inlet air In the simplest case, and for the smallest pans, the drying air can be drawn into the pan from the coating room. However, the suitability of the air will depend upon the type of coating process being carried out and the temperature and relative humidity of the air. It is unlikely to be suitable unless the coating is an organic solventbased film and the air is conditioned to about 30% to 35% r.h. at 20–22°C. Even if these conditions are met the additional load which the coating process will place on the air-conditioning system for the building should be evaluated before deciding to use localized environmental air. Generally, an inlet air system is required. This normally consists of a filter to remove coarse particles from the air which may be drawn from outside the building: a fan; a heat exchanger; a fine filter to prevent product contamination and a damper to regulate the air flow. In theory the exhaust fan should draw all its air from the inlet system. This would necessitate the coating pan being sealed, but if the door is opened to examine the tablets the inlet system would be by-passed. It is, therefore, preferable to install a fan with just sufficient power to overcome the resistance of the filters, heat exchanger and ducting. A hot air unit incorporating a fan, heat exchanger and filter, together with fan starter and the damper valve for the 10, 75 and 150 models are suitable for standing alongside the appropriate model and can be connected by a short length of ducting. Alternatively, they can be remotely sited. In the case of the larger 350 model a separate fan, heat exchanger and filter are incorporated into the inlet air-ducting system. 8.3 GLATT PERFORATED COATING PANS Glatt manufacture a wider range of coating pans than Manesty. These start with the laboratory coater with a capacity of 2.5 litres (1–2 kg) up to the GC 2000 with a capacity of 1250 litres (620–1000 kg). In general terms the concepts are similar but Glatt have developed the interchangeable pan option much further and they also provide more sophisticated automated washing systems. The laboratory coater GC 300 provides an easy to clean option and a built-in data-processing system. The pan can be easily removed for washing purposes. Fig. 8.8 illustrates this operation. [...]... a conveyor 8.6 PELLEGRINI COATING PANS These pans are marketed by GS Technology of Bologna, Italy, who supply the Page 225 Fig 8.17 Driam 1200 model coating pan expertise in air handling spray systems, controls and coating technology Pelligrini are the fabricators of the pan These are non-perforated pans with capacities from 10 to 1000 litres Originally developed for sugar coating, they use baffles... effect of coating different types and shapes of tablets? • What are the safety aspects? The initial tests should be conducted to derive basic pharmaceutical and mechanical data such as optimum shapes of tablets, coating times and drying air-handling requirements If tablet -coating equipment is considered, it can be divided into four parts: 1 2 3 4 the coating pan; the system that applied the coating; ... for coating a large range of particulate sizes from less than a Page 226 Fig 8.18 Driam auto cleaning system millimetre to tablets of all shapes and sizes It is claimed to be the best statistical mixer for coating available The GS control and coating systems can be fitted to any coating pan, be it Accelacota, Glatt, Driam, Hi-Coater, etc This control, it is claimed, results in dramatic decreases in coating. .. convey the tablets into the coating pan In automatic systems the tablets are usually transferred from an intermediate bulk container (IBC) which may be moved by an automated guided vehicle (or fork lift truck) or conveyed pneumatically from a silo to the coating pan The illustrations in Fig 8.11 shows a silo feeding tablets into the coating pan Page 217 Fig 8.10 Laboratory coating Pan Interchange System... Cleaning A schematic is shown in Fig 8.13 The cleaning system consists of a spray nozzle integrated into the coating spray arm for spraying the entire drum interior and a set of separate nozzles used to clean the pan exterior The cleaning liquid is collected in a tray below the coating pan This permits the coating pan and baffles to be immersed and rotated through the cleansing agent After completion of the... requirements of the coating solution to be sprayed and the tablet substrate A schematic of the Glatt system is shown in Fig 8.14 and the actual arrangement in Fig 8.15 Page 219 Fig 8.12 Automatic Control System for loading 8.4 DRIAM Driam claim that their unique system of controlling the drying air and reversing the flow at critical stages of the coating process provide advantages particularly when coating friable... dramatic decreases in coating times, particularly for sugar For film coating, GS have a special reciprocating piston pump, the speed of which is automatically controlled from the bed temperature For sugar coating, a modified GRACO pump is used The type of spray-gun, nozzle configuration and position above the bed is critical in all coating processes These are all either fully interchangeable or adjustable... is shown schematically in Fig 8.20 Page 227 Fig 8.19 Freund Hi-Coater 8.7 THE BUTTERFLY COATING PAN These pans have capacities ranging from 15 litres up to 1200 litres and are manufactured in Germany by Huttlin Originally developed for sugar coating, they are claimed to be suitable for all current types of film coatings, and in particular for larger tablets The Butterfly pan (Fig 8.21) has a special... attached by means of a simple fastener enabling the pan walls to be dismantled and the coating pan thoroughly cleaned As with the other types of coating pans, automatic control systems are available to monitor and optimize the process parameters 8.8 COLUMNS: FLUIDIZED BED As was mentioned in Chapter 1, fluidized bed coating columns were used in the early days by Abbott Laboratories based on the Wurster... parameters The type of column used by Merck in the manufacture of ALDOMET is shown schematically in Figure 8.23 Fig 8.22 Laboratory coating column Page 231 Fig 8.23 Schematic of a Wurster coating column The bottom air distribution plate is designed to assist the flow of particles during coating This is the most efficient way of utilizing the drying capacity of the air Unfortunately the tablets must be robust . and control of the coating process. 8.1 CONVENTIONAL COATING PANS It is not proposed to discuss in detail the use of conventional coating pans as these. produce a very dense bed in the coating pan which tends to reduce the batch size and increase the coating time. For sugar coating it should be remembered