Tài liệu Pharmaceutical Coating Technology (Part 8) pptx

Various methods have been used to improve the coating characteristics in this type of pan which was originally designed for sugar coating.. The batch size for each particular model will

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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

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

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Fig 8.2 Standard coating pan and a Pelligrini pan using the Glatt immersion-Sword system

Fig 8.3 Standard coating pan using the immersion tube system

Fig 8.4 Manesty Accelacota

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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

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

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

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

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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

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

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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 conditioning engineers to achieve this is the best option The fan and starter and a section of

air-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

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Fig 8.8 Glatt Coater GC300

Fig 8.9 Data acquisition system

The process parameters monitored by its data acquisition system are illustrated in Fig 8.9 This concept has been further extended to some of the larger laboratory models shown in Fig 8.10 The advantage of this type of system is that options for coating pellets and various sizes of tablets can be incorporated onto one machine by having pans with different size perforations The downside is the need to have a clean storage area available and a means of changing the pan from one size to another However, advantages in cost, floor space, cGMP and the different process development options clearly outweigh any disadvantages

8.3.1 Loading and unloading

These operations are illustrated in Fig 8.11 Manual loading, semi-automatic or automatic options are available and are controlled as shown in Fig 8.12

Several items of equipment are required In the semi-automatic operation it is necessary to have a lifting device to raise the product container to a height where it can be inverted into a funnel or similar transfer chute to 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

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

cleaning process the solution is drained and the drum is rinsed The cleaning of the spray

Fig 8.11 Automatic loading system

nozzles and supply tubing is included in the cleaning process Usually water pressure is sufficient for cleaning; however, where high-pressure water is needed, a pump can be fitted

Spray system

All spray systems need to be designed around 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

Fig 8.13 Glatt cleaning system

Driam manufacture a range of nonagonally shaped coating pans with capacities of between 5 kg and

600 kg The laboratory model, DRC 500/600 Vario, is equipped with an interchangeable pan which provides the flexibility of different operations:

2 The direction of the way the air is introduced can be reversed, the previous air inlet becoming the air exhaust and vice versa For example, when polishing is required after coating, the

polishing agent is introduced into the pan and the direction of the air is reversed To achieve a good polish it is necessary that the tablets rub against each other and the pan walls, and this

process is improved by low air pressure

3 This method results in good mixing of the tablets which, combined with the close control of spraying, gives a homogeneous coating

4 The air requirements are substantially lower when compared with other manufacturers’ units In conventional pans the air often strikes the product and is exhausted without any drying effect This cannot happen in the Driacoater, and consequently, with lower air requirements, there is a saving in energy costs

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Fig 8.14 Schematic of Glatt spray system

In the Varico combination unit it is claimed that the load can be reduced to 2.0 kg for coating in a similar way to the Driacoater 500 which was designed as a single unit for small batches of tablets of between 2 and 6 kg

The Driam differs from the Accelacota and Glatt coaters in the shape of the coating pan and the way the air is utilized in the drying process This is shown in Fig 8.16 On the outside of the drum covering the perforated areas, there are the air flow channels with removable covers At the rear of the pan the air channels are connected to the air distributor This distributor guides the drying air through the air

channels and the perforations into the product The direction of air flow is reversible

In contrast to the production machines, the laboratory unit is a complete and self-contained piece of equipment with built-in air supply and exhaust, steam heating, spray system, a completely contained cleaning system with pump, and all control and monitoring instruments The unit is mobile, requiring little space, and is operational after connections have been made to electric power, steam and

compressed air supply The air volume and the differential pressure in the drum are adjusted by the air control dampers in the air supply and exhaust system A built-in temperature control stabilizes the pre-set air supply temperature The casing, the drum and all parts in contact with the product are of 304 stainless steel A special stand is

• a range of capacities of 5 to 30 kg;

• a range of perforation inserts from 0.2 to 3.0 mm

• Direct Air Flow: Air is supplied through the perforated areas at the top of the pan and through the

product bed, and the air exhausted through the perforated areas under the product

• Reverse Air Flow: Air is supplied through the perforated areas at the bottom of the pan and

through the product bed It is exhausted through the perforated areas at the top of the pan or

through the hollow shaft at the rear