Tài liệu Pharmaceutical Coating Technology (Part 6) pdf

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

6 The development of film-coating processes

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:

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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

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

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

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

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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

SUSP’N USED

ATM

PRESS

FLOW RATE

ELAPSED TIME

Fig 6.4 Recorded data

INLET

TEMP OUTLET TEMP PUMP SPEED SUSP’N USED ATM PRESS FLOW RATE ELAPSED TIME

WEIGHT OF SUSPENSION USED=2502 GRAMMES ELAPSED TIME=71 MINS

Susp’n used – Suspension used

ATM Press – Atomizing pressure

Temp – Temperature

Fig 6.5 Schematic diagram of instrumented coating pan

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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 cm3

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

transitor oscillator which provides a stable signal A change in the transducer alters the capacitance in each of the tuned circuits, unbalancing the voltages across them A differential rectifier voltmeter across the tuned circuits provides a D.C signal from the change in pressure in the transducer This transmitter has an output of 0–10 V which is linear with respect to the air velocity

The Pitot tube consists of an impact tube whose opening when positioned in the duct faces directly into the stream of air to measure the impact pressure It should be sited in a section of duct at least 10 diameters from any bends or disturbances It is very sensitive to its position in the cross-sectional area of the duct

Computer

Generally an industrial unit should be used to generate graphics plus alphanumer-ics A feature of this operating system is a disc which allows a programme to read or write data in the background while simultaneously allowing transfer of data to the computer memory Process data is printed out as a hard copy

The printer enables process data to be presented in such a way that the user can obtain a hard copy of alphanumeric and graphic symbols, tabulated and formatted to suit any experimental requirement The paper can be positioned in the printer under command from the computer providing control of print width, decimal position, left and right margin control and many copies

The computer and its accessories can be interfaced with the sensors using an analogue to digital converter This interface is designed to accept data in one format and transmit data in another The computer requires data to be presented in a correct and logical format

Intratrace—a non-contact infrared digital thermometer

Any surface at a temperature above absolute zero emits heat in the form of radiated energy At

temperatures above 600°C some of this energy is visible but much of it is of longer wavelength than visible light (e.g infrared) although it behaves in a similar way to visible light The radiant flux from the surface is directly related to its temperature and it is this energy that the Infratrace measures The value can be visually displayed in Centrigrade degrees or it can be relayed by a suitable interface to a

computer and processed It may also be used to measure and record temperatures through glass by using the correct emissivity setting

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 taken to a metal band fitted around the shaft, but insulated from it The metal band acts as the plate of a capacitor, and a high-frequency electric field is generated between the band and the surrounding metal objects By using

a stationary high-impedance probe, it is possible to extract a signal from the field, coupled to the

oscillator without actual contact with the shaft