The present invention relates to a method for controlling a tablet press, whereby powder or granular material is compressed in dies arranged circumferentially in a rotary die table by means of reciprocating punches, said method comprising the steps:
consecutively supplying a quantity of material to be compressed into each die,
subjecting the quantity of material located in each die to a pre-compression and subsequently a main-compression,
whereby the main-compression is performed under substantially constant compression force and variable resulting tablet thickness of the individual tablets,
measuring a weight value of a parameter representative of the weight of the quantity of material fed into the die,
regulating the quantity of material supplied to each die on the basis of a deviation between a previously measured weight value and a first set value.
EP 1 584 454 A2 (Courtoy N V) describes a method for controlling a rotary tablet press, whereby, during the main-compression, a hardness value of the tablet resulting from the compression is measured, and whereby the degree of compression that the quantity of material located in each die is subjected to during main-compression is regulated on the basis of a deviation between a previously measured hardness value and a set value for the hardness. In this way, the mean tablet hardness of the produced tablets may be maintained within certain desired limits, although the resulting hardness of the individual tablets will vary slightly, which is indeed satisfactorily in most applications.
DE 198 28 004 B4 describes a method for obtaining a constant compression force in a tablet press having computer controlled and by means of step motors adjustable compression rollers, whereby one of the compression rollers during each single compression of a tablet is positioned by positive and negative displacements, so that a predetermined maximum compression force is maintained constant during a defined time. However, the document is silent about, how the amount of the necessary displacement of a compression roller is determined, and how it is determined, whether the displacement should be positive or negative. Because the necessary displacement is dependent on powder properties, it is necessary to determine the compression behaviour of each specific powder to be compressed, and this is in practice a mayor disadvantage. In any case, the real-time control of the position of the compression rollers by means of step motors would be a very expensive solution.
Furthermore, an industrial pellet press is known, whereby the main-compression is performed under substantially constant compression force and variable resulting pellet thickness of the individual pellets, and whereby the weight of the produced pellets is controlled by regulating the quantity of material supplied to each die on the basis of a measured value corresponding to the pellet thickness resulting from the main-compression of a previously produced pellet. However, although the hardness of the resulting pellets is very consistent, the weight control is not accurate enough for a pharmaceutical tablet press.
The object of the present invention is to provide a method for controlling a tablet press, whereby consistent tablet properties in terms of weight as well as hardness may be obtained.
In view of this object, the method according to the invention is characterized by measuring the weight value during pre-compression of the quantity of material located in each die.
By measuring the weight value during pre-compression, a more accurate measurement and consequently a more accurate weight control may be obtained. The measurement of a weight value during main-compression at constant compression force is less accurate than a measurement of a weight value during pre-compression, because the powder or granular material has already been compressed during pre-compression. Consequently, according to the invention, the weight may be controlled very accurately, and at the same time the density and thereby the hardness of the individual tablets may be maintained consistent.
This is very advantageous, especially if applied to a pharmaceutical tablet press, because in such a press controlling both weight and hardness is of great importance. A consistent tablet hardness means consistent disintegration and dissolution of the tablets when swallowed, so that a consistent release profile and hence bioavailability of the produced tablets may be obtained.
In an embodiment, the weight value corresponds substantially to a thickness of a tablet during pre-compression of said tablet under substantially constant compression force. At pre-compression, the compression force is relatively small, and therefore the measurement of a value corresponding to the thickness of a tablet gives a rather accurate measurement of the weight of the tablet. Because both the pre-compression and the main-compression of each tablet is performed under substantially constant compression force, the resulting density and therefore also the hardness of the individual tablets will be even more constant. A more constant tablet hardness means more constant disintegration and dissolution of the tablet when swallowed, so that a substantially constant release profile and hence bioavailability of the produced tablets may be obtained.
In an embodiment, the compression force of the pre-compression is maintained substantially constant by means of a pre-compression piston arranged displaceably in a gas cylinder, whereby the gas cylinder is supplied with compressed gas, and whereby the gas pressure in the gas cylinder is maintained substantially constant by means of a pressure regulator. By providing a suitable gas volume in the gas cylinder or in a separate vessel connected with this, the displacements of the piston will in practice hardly change the gas pressure in the gas cylinder, and consequently, the compression force will be maintained substantially constant in real time when the piston is moving without any response time of a computer control loop implicated.
In an embodiment, the powder or granular material is compressed in the die between opposed first and second punches, each punch having first and second ends, whereby said first punch ends are received in the die, and said second punch ends, during pre-compression, interact with first and second pre-compression rollers, respectively, whereby, during the pre-compression, the first pre-compression roller is displaced in the axial direction of the punches and the second pre-compression roller is fixed in said direction, and whereby the first pre-compression roller is carried by the pre-compression piston.
In an embodiment, the weight value corresponds substantially to a pre-compression displacement value representative of a displacement of the first pre-compression roller during pre-compression.
In an embodiment, the weight value corresponds substantially to the maximum compression force exerted by a punch on a tablet during pre-compression of said tablet to a predetermined tablet thickness.
In an embodiment, the compression force of the main-compression is maintained substantially constant by means of a main-compression piston arranged displaceably in a gas cylinder, whereby the gas cylinder is supplied with compressed gas, and whereby the gas pressure in the gas cylinder is maintained substantially constant by means of a pressure regulator. By providing a suitable gas volume in the gas cylinder or in a separate vessel connected with this, the displacements of the piston will in practice hardly change the gas pressure in the gas cylinder, and consequently, the compression force will be maintained substantially constant in real time when the piston is moving without any response time of a computer control loop implicated.
In an embodiment, the movement of the main-compression piston is stopped by a dampening force after each main-compression. Thereby, the rotational speed of the die table may be increased without increasing noise and vibrations.
In an embodiment, the dampening force is produced by a chamber containing compressed gas. The dampening force may thereby be varied by varying the pressure of the compressed gas.
In an embodiment, the chamber containing compressed gas is a hollow ring of elastic material located between the main-compression piston and an abutment.
In an embodiment, the dampening force is provided by a dampening piston arranged in a cylinder containing compressed gas. Thereby, the dampening force may be varied continuously by varying the pressure of the compressed gas, for instance by means of a pressure regulator connected with the cylinder.
In an embodiment, the dampening force is provided by a spring element.
In an embodiment, the dampening force is provided by an elastic O-ring located between the main-compression piston and an abutment.
In an embodiment, the dampening force is provided by an elastic ring having rectangular cross-section and being located between the main-compression piston and an abutment.
In an embodiment, the powder or granular material is compressed in the die between opposed first and second punches, each punch having first and second ends, whereby said first punch ends are received in the die, and said second punch ends, during main-compression, interact with first and second main-compression rollers, respectively, whereby, during the main-compression, the first main-compression roller is displaced in the axial direction of the punches and the second main-compression roller is fixed in said direction, and whereby the first main-compression roller is carried by the main-compression piston. In this way, without having to decrease the rotational speed of the die table, the dwell time of the tablets during main-compression may be increased, when compared to a prior art tablet press having fixed position of the main-compression rollers during compression. Increased dwell time may be advantageous in order to obtain greater tablet hardness. Furthermore, the formulation of the powder or granular material to be compressed may be reworked in order to improve the flowability of the material, whereby the lower compressibility that is the consequence of an improved flowability is compensated for by the increased dwell time. It is noted that flowability is inversely proportional to compressibility. The improved flowability of the material is an advantage during handling of the material upstream the die table of the tablet press.
In addition, a lower risk of tablet capping or tablet laminating may be obtained: an increase in dwell time will give more plastic deformation, because plastic deformation is time dependent. This plastic deformation will in turn increase the tablet strength, so that it can better withstand the elastic recovery after ejection of the tablet. By increasing the plastic deformation the ratio between plastic deformation and brittle fracture will become higher. Consequently, because too much deformation by brittle fracture might give capping and laminating problems, increasing the plastic deformation will give lesser capping or laminating problems.
Increasing the dwell time may give a better deaeration of the powder bed and a better, more uniform particle rearrangement at compression. This in turn will give less stress concentrations in the tablet. Less stress concentrations in the tablets will result in less tablets breaking in processing equipment downstream the tablet press, such as a tablet coater. This will in turn give less batch rejections. Less stress concentrations will also give less tablets breaking in packaging equipment, like blister lines, and this will lead to lesser machine downtime and a higher productivity.
Alternatively to increasing the dwell time, the rotational speed of the die table may be increased to arrive at the same dwell time as for the above mentioned prior art tablet press. Thereby, the production output rate may be increased.
The dwell time is the time during which the compression force is at its maximum. In a prior art tablet press having fixed position of the main-compression rollers during compression, the dwell time is consequently the time during which the flat end part of the second punch end rolls on the periphery of the main-compression roller and is therefore limited by the diameter of the flat end part. On the contrary, in a tablet press as described above, whereby the first main-compression roller is displaced during compression, the dwell time starts when the compression force balances the gas pressure in the gas cylinder, and the piston starts to move, which is before the flat end part of the second punch end starts rolling on the periphery of the main-compression roller. Correspondingly, the dwell time ends, when the piston stops moving and hits the abutment, after the flat end part of the second punch end has stopped rolling on the periphery of the main-compression roller. Therefore, in this case, the dwell time is not limited by the diameter of the flat end part.
In case of problematic tablet formulations, an increased dwell time or a faster rotational speed of the die table may be an advantage.
In an embodiment, a main-compression displacement value representative of a displacement of the first main-compression roller during main-compression is measured, and the position of the second main-compression roller in said direction is regulated on the basis of a deviation between a previously measured main-compression displacement value and a second set value. The more the first main-compression roller is displaced during compression, the larger dwell time is obtained, provided that the rotational speed of the die table is maintained constant. By regulating the position of the second main-compression roller, it is possible to regulate the resulting displacement of the first main-compression roller and thereby to regulate the dwell time. Thereby, the above-mentioned tablet properties dependent on the dwell time may be controlled, so that more predictable results are possible.
In an embodiment, said position regulation of the second main-compression roller is based on a mean value of several single measured main-compression displacement values. Thereby, fluctuations of the measured main-compression displacement value will not cause the control loop to overreact; instead, corrections to the position of the second main-compression roller will be based on progressive deviations registered by the control loop.
In an embodiment, the position of the second main-compression roller is maintained constant as long as said mean value of the main-compression displacement value falls within preset correction tolerance limits. This will further prevent a possible tendency of the control loop to overreact, as corrections will only be performed when a measured value falls outside the preset limits.
In an embodiment, the position of the second main-compression roller is regulated so that the resulting main-compression displacement value is maintained substantially constant. Thereby, the dwell time will also be maintained substantially constant, whereby the above-mentioned tablet properties dependent on the dwell time will be substantially constant.
The present invention further relates to a rotary tablet press comprising a housing and a rotary die table having a number of dies arranged circumferentially, each die being associated with first and second punches, each punch having first and second ends, said first punch ends being receivable in the die and arranged for compression of a powder or granular material in the die,
the housing comprising a feeding device for the supply of material to be compressed into the dies, a tablet discharge device for removal of compressed material in the form of tablets, and
at least one pre-compression station and at least one main-compression station, each said compression station being provided with first and second compression rollers adapted to interact with the second punch ends, respectively, in order to perform compression of material located in the dies by reciprocation of the punches,
the first main-compression compression roller of the main-compression station being supported by means of a main-compression piston arranged displaceably in a gas cylinder, the gas cylinder being connected to a supply of compressed gas, and a pressure regulator being adapted to maintain the gas pressure in the gas cylinder substantially constant,
the housing comprising a weight transducer for measuring a weight value of a parameter representative of the weight of a quantity of material fed into the die,
a powder quantity regulator being provided for regulation of the quantity of material supplied to each die by the feeding device on the basis of a deviation between a previously measured weight value and a first set value.
The rotary tablet press according to the invention is characterized in that the weight transducer is comprised by the pre-compression station. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the first compression roller of the pre-compression station is supported by means of a piston arranged displaceably in a gas cylinder, whereby the gas cylinder is connected to a supply of compressed gas, and whereby a pressure regulator is adapted to maintain the gas pressure in the gas cylinder substantially constant. Because both the pre-compression and the main-compression of each tablet is performed under substantially constant compression force, the resulting density and therefore also the hardness of the individual tablets will be even more constant. Thereby, a substantially constant release profile and hence bioavailability of the produced tablets may be obtained.
In an embodiment, the weight transducer of the pre-compression station has the form of a displacement transducer for measuring a pre-compression displacement value representative of a displacement of the piston in the gas cylinder. At pre-compression, the compression force is relatively small, and therefore the measurement of a value corresponding to the thickness of a tablet gives a rather accurate measurement of the weight of the tablet.
In an embodiment, a dampening element is provided between the piston of the main-compression station and an abutment. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the dampening element has the form of a chamber containing compressed gas. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the chamber containing compressed gas is a hollow ring of elastic material. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the dampening element has the form of a dampening piston arranged in a cylinder containing compressed gas. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the dampening element has the form of a spring element. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the dampening element has the form of an elastic O-ring. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the dampening element has the form of an elastic ring having rectangular cross-section.
In an embodiment, the main-compression station comprises
a displacement transducer for measuring a main-compression displacement value representative of a displacement of the piston in the gas cylinder, and
a position regulator for regulation of the position of the second main-compression roller on the basis of a deviation between a previously measured main-compression displacement value and a second set value. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, said position regulator is adapted to regulate the position of the second main-compression roller on the basis of a mean value of several single measured main-compression displacement values. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, said position regulator is adapted to maintain the position of the second main-compression roller constant as long as said mean value of the main-compression displacement value falls within preset correction tolerance limits. Thereby, the above-mentioned advantages may be achieved.
In an embodiment, the first main-compression roller of the main-compression station is located above the rotary die table. This is advantageous, if the space below the rotary die table is limited.
In an embodiment, the pressure regulator is adapted to maintain the gas pressure in the gas cylinder at or below 30 bars. Thereby, a simpler and consequently cheaper pressure regulator may be employed.
In an embodiment, the total weight of the first main-compression roller, the main-compression piston, a yoke carrying the first main-compression roller and supplementary parts displaceable with the main-compression piston is less than 30 kg. Thereby, the rotational speed of the die table may be further increased without increasing noise and vibrations.
The invention will now be explained in more detail below by means of examples of embodiments with reference to the very schematic drawing, in which
The tablet press is provided with a feeding device in the form of a well-known double rotary feeder with two not shown rotary paddles located in a feeder housing and driven by means of separate drive motors providing for independent speed setting of the paddles. The feeder housing is open against the die table so that the paddles may ensure proper filling of the dies with feedstock. Other feeding systems may also be employed, such as a so-called gravity feeder or a vibration feeder.
In the control unit, the displacement signal supplied for each tablet produced is compared with predetermined rejection tolerance limits defining the maximum acceptable deviation from a desired tablet weight. If the displacement signal for a tablet falls outside the rejection tolerance limits, a rejection signal is sent from the control unit to a rejection device associated with a tablet discharge device, and the tablet is separated from the remaining tablets, when it reaches the rejection device, see
In the powder quantity regulator, a rigid or floating mean value of the displacement signal for several consecutive tablets is compared with a first set value that corresponds to a calibrated desired tablet weight and is received from the control unit. If the deviation falls outside preset first correction tolerance limits, the fill depth signal supplied to the feeding device is corrected correspondingly. Said correction tolerance limits may be calculated automatically by a general control system on the basis of user defined acceptable deviations, for instance in the form of percentage values, from the desired tablet weight.
From the tablet discharge device the tablets are fed to an automatic testing device, for example a Kraemer Electronic Tablet Tester, in which the weight and hardness of a number of sample tablets are determined periodically, and whereby corresponding weight and hardness signals are transferred to the control unit, see
Alternatively, the pre-compression station 10 may have a fixed distance between the lower compression roller 11 and the upper compression roller 12, and the displacement transducer 15 may then be replaced by a strain gauge provided on the shaft of one of the compression rollers 11, 12 and by means of which a force signal is supplied to the powder quantity regulator and the control unit. The force signal then constitutes the weight value representative of the weight of the quantity of material fed into the die.
The vertical position of the piston 21 is measured by means of a displacement transducer 23, such as a LVDT (Linear Variable Differential Transformer). When an upper punch 5 passes under the centre of the upper compression roller 20, the displacement transducer 23 measures a displacement substantially corresponding to the thickness of the tablet after the main-compression. The displacement measured by the displacement transducer 23 is also representative of the dwell time, that is, the period of time during which the tablet is compressed by the maximum constant compression force. At each main-compression of a tablet, the displacement measured by the displacement transducer 23 is transferred in the form of a displacement signal to the dwell time regulator and the control unit; see
In the dwell time regulator, a rigid or floating mean value of the displacement signal for several consecutive tablets is compared with a second set value that corresponds to a calibrated desired tablet dwell time and is received from the control unit. If the deviation falls outside preset second correction tolerance limits, a bottom roller height signal is generated and transferred to the main-compression station 17. In the main-compression station 17, the bottom roller height signal is fed into a linear actuator 19, which adjusts the height of the bottom compression roller 18 correspondingly; see
The dwell time regulation may counteract the tendency of the dwell time to change as a result of changing compacting properties of the material compressed in the die. Changing compacting properties may be the result of a change in the humidity, the temperature, and the mean particle size over a batch, etc. However, according to the invention, the dwell time regulation may be omitted, and satisfying tablet properties may nevertheless be obtained.
In the control unit, the hardness signal received from the automatic testing device is compared with the desired tablet hardness, and on the basis of the deviation between these values, a re-calibration may be performed by adjustment of the second set value supplied to the dwell time regulator by the control unit. Alternatively, said re-calibration could be performed by adjustment of the otherwise constant air pressure in the air cylinder 22 of the main-compression station 17.
As it is seen in
Obviously, the invention is equally applicable to so-called single-sided, double-sided or multi-sided tablet presses. For instance, in a double-sided press for the production of tablets having two layers, a first layer production section and a second layer production section, arranged along opposite sides of the die table, each has both a pre-compression station and a main-compression station. In this case, however, the first layer is compressed to a fixed thickness at main-compression in order to better be able to regulate the quantity of the second material supplied to each die. A substantially constant hardness of the entire tablet is obtained by performing the main-compression of the second layer under substantially constant compression force and variable resulting tablet thickness of the individual tablets, in the same way as explained above for a single-sided press. Similarly, in a press for production of tablets having more than two layers, the main-compression is performed under substantially constant compression force and variable resulting tablet thickness only for the last layer of the tablet. The other layers are compressed to a fixed thickness at main-compression.
In a double-sided press for the production of single layer tablets, two similar production sections each corresponding to that of a single-sided press are provided, arranged along opposite sides of the die table, and each has both a pre-compression station, a main-compression station, a feeding device, and a tablet discharge device. Each production section is provided with both a powder quantity regulator and a dwell time regulator.
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WO2007/132281 | 11/22/2007 | WO | A |
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