Page 152 6 The development of film-coating processes Graham C.Cole SUMMARY To develop a film-coating process requires a laboratory test rig that can be scaled-up to meet production requirements. All the process parameters need to be optimized. A scheme is discussed here that provides an integrated computer-controlled system designed for aqueous film coating in a side-vented pan. A comparison is made of energy requirements of a column-coating system and a coating pan. All the major operational coating parameters can be measured and recorded under the overall control of a microcomputer. The monitored values are displayed on a computer screen at selected short intervals, e.g. 5 s, and, at selected longer intervals, e.g. 1 min, they can be printed as hard copy. This chapter describes the selection of instruments to measure the appropriate parameters; how the coating process may be optimized using a laboratory side-vented pan; the loop closed to provide automatic control, and the process scaled-up to control successfully the coating of production size batches. 6.1 INTRODUCTION To set up a suitable experimental rig required for the general development of all coating processes, instruments are required to measure and record data from the process parameters. First it is necessary to determine which parameters have a critical effect on the performance of the coating system to produce a tablet that is pharmaceutically acceptable. The following process parameters are possibilities: Page 153 After conducting a number of preliminary experiments, a number of these parameters can be rejected as they do not critically affect the appearance and quality of the film-coated tablet. This list is then reduced to ten which, by installing the appropriate instruments, are used to record the raw data. These instruments are linked through an analogue-to-digital converter to a computer and printer and the values for each parameter recorded on a specifically numbered channel. These are designated the critical parameters. Each can easily be scanned, measured and recorded. The next stage in the set-up of the test rig is the selection of a coating pan, coating accessories, instruments, computer and printer. An example is a model 10 Accelacota (Manesty Machines Ltd). However, any suitable manufacturer’s • Inlet air flow rate. • Inlet air temperature. • Inlet air humidity. • Outlet air flow rate. • Outlet air temperature. • Outlet air humidity. • Leakage air rate to the atmosphere through the casing. • Spray concentration. • Spray temperature. • Spray flow rate. • Quantity of attrition from cores (by filtration of the exhaust air). • Quantity of spray not applied to tablets (by filtration of the exhaust air). • Tablet-bed temperature. • Power/torque to keep the drum turning. • Rotational speed of the drum. • Electrical power consumption of fans. • Heat input to inlet air. • Pressure drop, inlet-outlet airstream. • Atomizing air pressure. (The atomizing air flow can be neglected as a calculation will show that it is less than 2% of the total air throughput.) Channel 0 Coating spray rate. 1 Inlet air flow rate. 2 Inlet air temperature. 3 Outlet air flow rate. 4 Outlet air temperature. 5 Outlet air dew-point. 6 Fan rotational speed. 7 Coating drum drive torque. 8 Coating suspension temperature. 9 Tablet surface temperature. 10 Atomising air pressure. 15 10-volt reference source. Page 154 coating pan could be used, depending on the objectives of the coating development programme. 6.2 DEVELOPMENT OF THE EXPERIMENTAL RIG The coating pan As an example, a model 10 Accelacota could be used. A unit is shown diagrammatically in Fig. 6.1. The unit 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 turned over and also mixed laterally. There are baffles to assist this stirring action. Hot drying air enters the drum through the perforations on the side remote from the tumbling tablet bed, and is drawn through the bed by a fan in the exhaust plenum. 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, they are of the same shape but of different size for each model and can be easily removed or replaced with baffles of different design, depending on the physical Fig. 6.1 Schematic diagram of Model 10 Accelacota. Page 155 characteristics of the tablet to be coated, e.g. friability, and the properties that the coat is designed to impart to the tablet, e.g. enteric coating. In this case the degree of mixing becomes a critical parameter. A means is required of applying the coating suspension or solution and storing it during application to ensure that it remains homogeneous. Most manufacturers supply suitable units. A typical unit designed for the application of aqueous filmcoating solutions and suspensions is shown in Fig. 6.2 . The controls are mounted on the top face of the unit and comprise gauges for pump speed, fluid pressure, atomizing air pressure and on/off switches. Below each gauge is the regulator which controls the circuit to which the pressure gauge applies. The adjustment is effected by rotating the main control knob of each regulator while the adjustment is secured by the inner lockscrew. On the panel there are also two valves controlling the flow and return of coating solution. The operation of the unit is briefly as follows: Compressed air is supplied to the air inlet manifold and from there to three different internal supplies. One supply passes through an air-pressure regulator to the liquid pump and the pressure of this air is shown on the pump air-pressure gauge. This pressure governs the pressure of the liquid. A second air supply passes through a regulator which controls the atomizing air-pressure gauge and the air is then supplied direct to the atomizing air connection on the spray bar in the coating pan. Also connected into this circuit is a Fig. 6.2 Spray unit control unit. Page 156 pressure stop valve which controls the signal air to the spray bar. The signal air is used to provide an option for stopping and starting the spray. In some cases continuous spraying results in overwetting. The third air supply taken from the air inlet manifold passes through an air-pres-sure regulator which feeds air to two air-controlled diaphragm type fluid-pressure regulators. Two regulators are necessary to supply the relatively large volumes of fluid used on the larger models of coating pans. This method of control has been employed so that there is no differential pressure between the outputs from the two regulators. Coating fluid is picked up from the storage container by a peristaltic pump, and pumped at pressure to the fluid-pressure regulators where the supply pressure is controlled and maintained. This pressure is shown on the fluid-pressure gauge. The coating solution is then fed through a valve to the coating pan spray bar, spray nozzle and the excess is returned by means of a second pipe, through a second valve, to the solution container. In the case of low-viscosity liquids, the return control valve can be used to create a back pressure in the system to keep the flow rate constant. The flow is controlled by: This arrangement is versatile and easy to clean. No metal surfaces of the pumping system are in contact with the coating suspension during the spray operation, which reduces the risk of cross- contamination. It is possible to control the speed of the pump by linking it to a signal such as the temperature of the exhaust air, inlet air or tablet-bed temperature. One way of controlling the process is to use the exhaust temperature as a controlling parameter as this is an indirect measure of the tablet-bed temperature and is sensitive to process changes. By using a minimum exhaust temperature of 35°C and linking the spray rate directly to this temperature, the pump would automatically stop if the temperature fell below this level. For each degree rise in temperature above this level the speed of the pump increased, up to a maximum of 50 rev/min thus increasing the spray rate. This relationship is illustrated in Fig. 6.3 . The relationship between these three variables is inserted as an instruction in the computer programme. By altering this instruction different spray rates can be obtained, depending on the size of the coating pan used and the spray rate required. It can also be demonstrated that a balance can be achieved between the inlet temperature, exhaust temperature and spray rate during the coating operation. To do this a simplified programme must be written to provide automatic control of the coating process. For example: 1. the speed of the pump; 2. the internal diameter of the flexible silicone tube which provides a range of flow rates from 0.002 to over 8 g/s; 3. the nozzle setting. Channel 0 Inlet drying air temperature °C 1 Outlet drying temperature °C Page 157 Fig. 6.3 Relationship between pump speed, temperature and spray rate. The advantage of a computer-based system means that these parameters can be scanned and measured rapidly, say every 5 s, and displayed on the VDU. The results can then be recorded every minute, and every 5 min the spray flow rate can be calculated and recorded. An example of part of the type of a printout is shown in Fig. 6.4 . At the completion of the coating process and when a predetermined quantity of coating suspension has been applied, a ‘batch completed’ sign is flashed onto the VDU, the pump is automatically switched off and a summary of the processing parameters recorded on the printout. This process and control programme is schematically represented in Fig. 6.5 . The spray bar fitted to larger coating pans consists of three chambers, one of which contains the coating fluid, one the atomizing air, and one the signal air. The spray guns are mounted directly on the chamber which contains the coating solution and separate pipe connections are made between the gun and the two air chambers. 2 Pump speed rev/min 3 Coating suspension used kg×10 −3 4 Atomizing air pressure lb/in 2 or bar Page 158 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 40 10 1399 30 34 40 MIN. 60 39 10 1442 30 60 39 10 1484 30 60 39 10 1526 30 60 39 10 1526 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 39 10 1569 30 34 45 MIN. 60 39 10 1611 30 60 38 10 1654 30 59 39 10 1696 30 59 38 10 1738 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 38 10 1738 30 34 50 MIN. 59 38 10 1781 30 59 38 10 1823 30 61 38 10 1866 30 61 38 10 1908 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 61 38 10 1950 30 42 55 MIN. 60 38 10 1993 30 60 38 10 1993 30 60 38 10 2035 30 60 38 10 2078 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 38 10 2120 30 34 60 MIN. 60 38 10 2120 30 60 38 10 2162 30 60 38 10 2205 30 60 38 10 2247 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 38 10 2290 30 34 65 MIN. 59 39 10 2290 30 60 38 10 2374 30 60 39 10 2374 30 Fig. 6.4 Recorded data 60 38 10 2417 30 INLET TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM. PRESS. FLOW RATE ELAPSED TIME 60 38 10 2459 30 34 70 MIN. WEIGHT OF SUSPENSION USED=2502 GRAMMES ELAPSED TIME=71 MINS Susp’n used – Suspension used ATM. Press – Atomizing pressure Temp – Temperature Page 159 Fig. 6.5 Schematic diagram of instrumented coating pan. Page 160 The spray gun is an automatic unit with micro- adjuster for spraying. Connections are provided for the supply of coating solution, atomizing air, and signal air. 6.2.1 Instrumentation The following are examples of instruments that can be used, giving a general approach to what should be done. Many scientists will have their own preference so the choice here should not be considered as cast in stone. Dew-point hygrometer This hygrometer is of the optical condensation type. In this instrument a surface is cooled by a thermoelectric or Peltier cooler until dew or frost begins to condense on a mirror. The condensate surface is maintained electronically in vapour pressure equilibrium with the surrounding gas, and surface condensation is detected by an optical or an electrical technique. The condensation surface, when maintained at the temperature at which the rate of condensate exactly equals the evaporation, is then the dew-point temperature. Such a sensor is a fundamental measuring device. The temperature of the surface when so controlled is typically measured with a platinum resistance thermometer, thermocouple or thermistor embedded in the mirror surface. The main drawback of this type of hygrometer is its complexity and high cost when compared to most other humidity sensors. It is also subject to contamination by materials other than water condensing on the cooled surface. Air flow measurement The air flow is measured by two turbine flow meters, a Pitot tube and a differential pressure transmitter. Because of the problems of obtaining reliable air flow measurements, two straight circular cross- sectional sections of duct should be built to incorporate the turbine flow meters: one for the inlet air and one for the exhaust duct air. The meters must be inserted at a position in the ducts to ensure fully developed air flow using the total flow rate calculated from the velocity distribution across the section. This inlet air duct plus the meter assembly needs to be calibrated. The second turbine flow meter, mounted in the exhaust, can be calibrated against the first meter. Good correlation is obtained when the coating pan is completely sealed and no air leaks into the pan from the environs. Pitot tubes determine local or point velocities by measuring the difference between impact pressure and static pressure. In use the Pitot is connected to a low-pressure transmitter which operates on a diaphragm capacitance principle. Two pressure cavities are separated by a taut metal diaphragm with an electrode supported close to it on either side producing two air di-electric capacitors. A pressure difference between the cavities deflects the diaphragm changing the capacitance of the circuit. The volume displacement for full-scale definition is typically 0.003 cm 3 . The capacitors on either side of the diaphragm form two tuned circuits with inductors in the circuit board. These tuned circuits are equally coupled to an R.F. [...]... worked example is designed to show what energy is required during the coating process when two different types of equipment are used 6.4.1 Energy balance A comparison of the energy requirements for heating the drying air in a 1500 mm diameter pan and a 450 mm diameter fluidized bed film -coating column (see Table 6.3) suggests that the coating pan was excessively inefficient in its use of the hot air for... 40 22.4 44 36 18.3 42 41 22.6 37 26 17.8 32 27 20.8 47 38 16.1 38 37 21.5 35 26 14.5 36 34 21.0 32 23 Page 165 Table 6.3 Energy balance: comparison of a 1500 mm diameter coating pan and a 450 mm fluidized bed coating column 1500 mm coating pan 450 mm column Drying air volume (m 3/h) 8500 2000 Drying air mass (kg/h) 9010 2120 Inlet air temperature (K) 333 344 Outlet air temperature (K) 313 326 Temperature... used These are: • Spray drying of the film coat before it is deposited on the tablet • Excessive loss of coating materials due to spray drying • Contamination of the exhaust system with large quantities of film coating due to the spray drying effect, resulting in increased maintenance costs • Excess coating material deposited on the pan walls 6.5 ENERGY RECOVERY This is an example of how to analyse, calculate... frequency modulation model operating at a centre frequency of 22 kHz The demodulated signal is displayed on a meter It can be used with a UV recorder from a 50 Hz mains supply 6.3 COATING VARIABLES The processing parameters for coating can be divided into two groups: independent and dependent 6.3.1 Independent variables Four independent variables can be considered to have a direct effect on the quality... drying purposes The following analysis does tend to support this criticism superficially, but it does not take account of the improvement in product quality achieved by using the side-vented coating pan If the cost of coating 1 000 000 tablets (344 kg) of product in the 1500 mm model is considered and the following parameters apply where Cp is the specific heat of air at constant pressure (kJ/kg K), and... conservation is a major concern of all companies and tablet -coating systems use a large volume of drying air which is usually exhausted to atmosphere at temperatures between 35 and 60°C Depending on the location of the plant and the temperature of the environmental air outside Page 167 the plant, this air needs to be heated on the inlet side of the coating pan to between 50 and 90°C This can mean that air... (enthalpy) between exhaust air and outside air represents an energy loss Typical examples of equipment used where energy losses through an air exhaust system occur are: tray dryers, fluid bed dryers, coating pans, coating columns and building heating/cooling systems and dust control systems The most important factors for determining the energy losses are: air quantity, temperature and relative humidity For... exhaust fan Processing time Total energy =2.5 hours =95×104+11.6×104 kJ =106.6×104 kJ If the cost of 1 kilowatt hour (kWh) of electricity is approximately £0.03 (1 kWh =3.6×103 kJ), then: The cost of coating one batch of tablets in the 1500 model is approximately £9, assuming 100% utilization of the heat content of the drying air This is 0.9p per 1000 tablets The energy lost is the difference between... ambient temperature The process time is 2.5 hours Cost=163×0.03, where 1 kWh costs £0.03 Total cost of lost energy=£4.9 This is equivalent to a loss of 0.49p per 1000 tablets or 55% of the total energy coating cost From this it can be seen that there is a potential saving from recovering energy from the exhaust systems However, the use of higher volumes of air results in a faster process and a more elegant... Telemeter A short range telemetry system can be used to measure strains and temperature It consists of an oscillator and a discriminator A possible requirement is the measurement of shaft torque on the coating pan The oscillator and its battery are connected to a suitable strain gauge bridge fixed to the shaft The earth side of the battery is connected to the shaft, and the output from the oscillator . film coating in a side-vented pan. A comparison is made of energy requirements of a column -coating system and a coating pan. All the major operational coating. Page 154 coating pan could be used, depending on the objectives of the coating development programme. 6.2 DEVELOPMENT OF THE EXPERIMENTAL RIG The coating