GB2423975A

GB2423975A - Making capsules by dielectric welding

Info

Publication number: GB2423975A
Application number: GB0504725A
Authority: GB
Inventors: Allan Draisey
Original assignee: INGEL TECHNOLOGIES Ltd
Current assignee: INGEL TECHNOLOGIES Ltd
Priority date: 2005-03-08
Filing date: 2005-03-08
Publication date: 2006-09-13
Anticipated expiration: 2025-03-08
Also published as: GB2423975B; GB0504725D0

Abstract

Capsules (30) are made using films (18) of a water-soluble or digestible polymeric material, by deforming the films to form a multiplicity of enclosures between a pair of rotary welding dies (14 and 15), and filling the enclosures with a flowable filling material. The films are welded by dielectric welding at the rotary welding dies. Radio frequency power is coupled to or from each rotary die (14 and 15) through a respective multi-plate capacitor (28), each of which includes a multiplicity of spaced-apart parallel flat plates (50, Figure 3) arranged to rotate with the die (14 or 15), and a multiplicity of non-rotating plates (60, Figure 3) interleaved between them. The capsules may be used for pharmaceutical compounds.

Description

Capsules This invention relates to a process and an apparatus for forming

capsules, for example for the delivery of pharmaceuticals.

A variety of pharmaceuticals and other materials are delivered in capsules. Both liquid and particulate material may be enclosed in soft capsules, these capsules being made from films of a soft elastic polymer which are brought together between rotating dies that have cavities in their surfaces. The material to fill the capsules is supplied between the films as the films deform into the cavities; as the dies turn the films come together and are sealed together by application of heat and/or pressure at the dies. This rotary die process is widely used for gelatin capsules, the dies simultaneously shaping, sealing and cutting out the capsules. WO 01/68032 (Stanelco Fibre Optics) describes a way of using rotary dies to form capsules, in which a radio frequency voltage is applied between the dies, so that the films are bonded by dielectric heating. However, the methods that it describes for coupling the RF to the dies have not been found to be entirely satisfactory.

According to the present invention there is provided a process for making capsules, the process using films of a water-soluble or digestible polymeric material, and the process comprising the steps of deforming the films to form a multiplicity of enclosures between a pair of rotary welding dies, filling the enclosures with a flowable filling material, welding the films together by dielectric welding at the rotary welding dies to form a multiplicity of enclosures containing the filling material, wherein radio frequency signals are coupled to at least one of the rotary dies through a respective multi-plate capacitor, the capacitor comprising a multiplicity of spaced-apart parallel flat plates arranged to rotate with the die, and a multiplicity of non-rotating plates interleaved between them.

The present invention also provides an apparatus for making capsules, using films of a water-soluble or digestible polymeric material, the apparatus comprising a pair of rotary welding dies defining recesses, means to feed the films between the dies, the films deforming into the recesses so as to define enclosures, means to fill the enclosures with a flowable filling material, and means to couple radio frequency signals to the rotary welding dies so that the films undergo dielectric welding to form a multiplicity of enclosures containing the filling material, wherein radio frequency signals are coupled to at least one of the rotary dies through a respective multi-plate capacitor, the capacitor comprising a multiplicity of spaced-apart parallel flat plates arranged to rotate with the die, and a multiplicity of non-rotating plates interleaved between them.

The films may be caused to deform into the recesses by suction, for example by connecting a vacuum to the recesses, or alternatively the films may be caused to deform by the pressure of the filling material. The base of each recess need not correspond to the shape of the capsule, as the films need not contact the base of the recesses during formation of the enclosures. Once the enclosures have been welded together, they may be cut out from the remaining film to form capsules.

The rotary welding dies act as opposed electrodes, to which the high frequency electrical supply is provided. The supply may in principle be at a frequency between 1 MHz and 200 MHz, usually between 10 MHz and 100 MHz, but stringent limits are imposed on any emitted radio waves. In practice therefore the choice of frequency may be more limited. For example the supply frequency may be 27.12 MHz, or 40.68 MHz.

Preferably the capacitor plates that rotate with the die are circular or annular. They may for example be at a separation of between 1 and 3 mm, for example 2 mm.

They may for example be of aluminium, copper or brass.

They may be coated with an insulating material, or sheets of an insulating material that is unaffected by the RF may be interleaved between the rotating and non-rotating plates. Preferably no such dielectric material is provided, so that there is only air between the interleaved capacitor plates. Preferably each rotary die is provided with such a multi-plate capacitor. The RF power required for welding at the dies is thus transmitted through the multi-plate capacitors.

Each rotary die may be substantially cylindrical, and rotate about a fixed axis of rotation. The dies may be arranged to form one capsule at a time, forming the multiplicity of recesses in succession as the dies rotate. Alternatively the dies may be arranged to form a plurality of capsules at once, side-by-side across the width of the films; for example the dies may define close packed arrays of recesses. A heater may be associated with the rotary dies, to provide heating of the films to soften them, before they are deformed to form the recesses.

The filling material may be a pharmaceutical, and is a preferably a liquid. Where the capsules are intended to be swallowed (for example where they contain a pharmaceutical or a nutritional supplement), the polymeric material should be ingestible. It may for example be gelatin, or a water-soluble cellulose derivative. For example it may be hydroxypropyl methyl cellulose, which is approved for use with pharmaceuticals and in food (being indicated by the code E464 in Europe) Other suitable cellulose derivatives are hydroxypropyl cellulose (E463), and methyl ethyl cellulose (E465) Other suitable polymeric materials would be edible seaweed-derived polymers such as sodium alginate (E401), propylene glycol alginate (E405) or agar-agar (E406) . The polymeric material must not contain any harmful or toxic additives, but may contain compounds such as glycerol (E422) or glycerol monostearate (E47l) as plasticisers, these compounds also being ingestible and dispersible or soluble in water. Indeed the presence of such plasticisers is beneficial to the capsule-forming process.

There is no requirement for any water to be added to the film, and indeed it is preferable that the films should be at least superficially dry, that is to say in equilibrium with ambient conditions. For example the film might be in equilibrium with air at a temperature of 25 C and a relative humidity of 40%. For example it might be stored before use in a controlled humidity environment, with a relative humidity preferably in the range 30% to 70%. Under such circumstances the film would evidently incorporate some water but would appear complete dry, and such incorporated water would tend to act as a plasticiser.

During the welding process different parts of the films are heated to different temperatures, and there is subsequently a tendency for the web to deform as it cools down. Cutting out the capsules as they pass through the welding dies avoids this problem, although the cutting process may be easier once the welded seams have cooled at least slightly. Transferring the web and attached capsules directly to another die, so that the capsules remain located in recesses in one or other of the dies throughout the process, ensures that any tendency of the web to deform does not have a deleterious effect on the cutting process. Where the cutting is performed by a second pair of dies, one die of the second pair may also be one of the welding dies, or alternatively the second pair may be two additional dies.

The invention will now be further and more particularly described, by way of example only, and with reference to the accompanying drawings in which: Figure 1 shows a side view, partly in section, of an apparatus for forming capsules; Figure 2 shows a circuit diagram of part of the apparatus of figure 1; Figure 3 shows a plan view of a capacitive coupling for one of the dies in the apparatus of figure 1; and Figure 4 shows a sectional view on the line 4-4 of figure 3.

Referring to figure 1 this shows schematically an apparatus 10 for making capsules of an ingestible, pharmaceutical grade material, such as hydroxypropyl methyl cellulose, the capsules being fIlled with a nonaqueous liquid filling material 12. The apparatus comprises two adjacent rotary dies 14 and 15, each of generally cylindrical external shape, which define a plurality of oval recesses 16 in their periphery (8 recesses, as shown, along a peripheral path), the rotations of the dies 14 and 15 being synchronized so that the recesses 16 are always opposite each other.

Heaters (not shown) are arranged to maintain the dies 14 and 15 at a temperature between 50 and 7000, for example 60 C. Two sheets 18 of the polymeric material (hydroxypropyl methyl cellulose and a plasticiser in this example) are supplied to the dies 14 and 15 from rollers 20, each sheet 18 being of uniform thickness 0.20 mm. The dies 14 and 15 are of the same length as the width of the films 18, and may have other sets of recesses spaced axially along their length. It will be appreciated that the numbers of recesses 16 around a periphery is a matter of choice, and that if there is more than one peripheral ring of recesses, then the arrangement of those recesses 16 as an array over the surface of the dies 14 and 15 is also a matter of choice; they may for example be in a close packed array. The axes of rotation of the dies 14 and 15 are spring loaded towards each other (though prevented by stops (not shown) from touching each other), so the films 18 are subjected to compression as they pass between the dies 14 and 15.

Immediately above the two dies 14 and 15 is a guide block 22, the films 18 passing between the lower curved surface of the guide block 22 and the outer surface of the dies 14 and 15. The filling material 12 is fed through ducts 24 in the guide block 22 into the gap between the films 18 just above the point where they come together, each duct 24 being aligned with one of the sets of peripheral recesses 16. The films 18 are softened by their contact with the heated surface of the dies 14 or 15, and as the filling material 12 is injected the films 18 deform into the recesses 16 above the pinch point.

Hence the filling material 12 fills the recesses 16 at this point.

A high frequency generator 25 which generates an electrical signal at a frequency of 27.12 MHz is connected via a matching network 26 and a capacitative coupling 28 (represented diagrammatically) to the die 15.

The other die 14 is connected via another capacitative coupling 28 to earth potential. In operation of the apparatus 10 the generator 26 continuously supplies this high frequency signal, so that as the films 18 pass between the dies 14 and 15 they are subjected to dielectric welding. The opposed faces of the sheets 18 become hot enough to fuse together, whereas the outer faces in contact with the dies remain at the temperature of the dies 14 and 15. Thus in operation the films 18 are welded together as they pass through the pinch point between the dies 14 and 15. Filled capsules 30 hence emerge from below the rotary dies 14 and 15. The dies 14 and 15 preferably incorporate means to cut the capsules out from the remaining web of the films 18.

Many variations and modifications may be made to the apparatus described above without departing from the scope of the present invention. For example three sheets might be welded together in a single operation, with recesses in the outer sheets, so that a two-compartment capsule could be produced in which each compartment held a different material. Pharmaceutical grade cellulose derivatives are highly preferred, but other materials such as gelatin may be used.

Referring now to figure 2, the radio frequency signal generator 25, which is a solid-state device, supplies the radio frequency signal via a coaxial cable 32 to the matching network 26, from which the signal is supplied to the coaxial cable 34 (and so to the die 15) The matching network 26 is shown in more detail. The signal passes through a monitoring circuit 35 (shown diagrammatically), a variable capacitor 36, an inductor 37, and a variable capacitor 38, and so to the cable 34.

The monitoring circuit 35 monitors the radio frequency current and voltage, and adjusts the values of the variable capacitors 36 and 38 using servo-motors 40 and 41 50 that the impedance presented to the generator 25 remains at a constant value such as 50. A capacitor 42 connects the junction between the capacitor 36 and the inductor 37 to earth potential, and by switching in other capacitors 43 and 44 the effective capacitance between this junction and earth can be adjusted. This has the effect of finely adjusting the radio frequency voltage applied between the live electrode (die 15) and the opposed, earthed electrode (die 14), and the RF current supplied. It thus controls the power that is actually supplied between the dies 14 and 15.

The capacitative couplings 28 are actually multiplate air capacitors. Referring now to figure 3, one such coupling 28 is shown in plan. It includes fifteen annular brass plates 50 (only seven are shown) each of thickness 0.5 mm and of external diameter 100 mm.

Referring also to figure 4, these plates 50 are stacked alternately with annular brass spacers 52, 2 mm thick and of external diameter of 50 mm, on a brass hub 54 with a large flange 55 at one end, and are secured by bolts 56.

The brass hub 54 has a keyway so it locates securely on the drive shaft 58 for the adjacent die 14 or 15.

Consequently the plates 50 all rotate with the adjacent die 14 or 15.

Fourteen generally rectangular brass plates 60 (only six are shown), each of thickness 0.5 mm, of height 110 mm and breadth 65 mm, but with a semicircular cutout of diameter 60 mm on one of the long sides, are also stacked alternately with brass spacers 62, 2 mm thick and 110 mm by 12 mm, and are clamped together by two bolts 64 supported by two insulating plastic plates 66. One of the brass spacers 62 is integral with an electrical connector 63. As shown in figure 4, these plates 66 are connected together by a cross member 67 which is supported on a base plate 68; the cross member 67 can slide in a rectangular groove 70 along the base plate 68 to adjust the position of the plates 60.

As is evident from figure 3, the brass plates 60 locate in the gaps between the brass plates 50, and lie in parallel planes. The electrical connector 63 is connected to the cable 34 (assuming this coupling 28 is that for the die 15; if it is the die 14, then the connector 63 would be connected to the earth lead), so that the RF signal is supplied to each of the rectangular plates 60, and the signal is consequently capacitatively coupled to the annular plates 50 and hence to the die (14 or 15) . It will be appreciated that the power transmission to the dies 14 and 15 can be adjusted by adjusting the degree of overlap between the annular and rectangular plates 50 and 60. In the figures the overlap is at maximum, being about half the area of each annular plate 50, but the area of overlap can be reduced by sliding the cross member 67 in the base plate 68.

In use it has been found that such a coupling 28 gives adequate power transfer, and, because of the lack of physical contact between the rotating plates 50 and the stationary plates 60 there is no tendency to erode or to generate sparks. It will also be appreciated that if the air between adjacent plates 50 and 60 is heated by the RF, it is free to undergo convection because of the size of the gaps. It will be understood that the capacitative couplings 28 are effectively in series with the adjustable capacitor 38 in the matching network 26.

- 10 - Consequently the value of that adjustable capacitor 38 and/or the value of the capacitance to earth (i.e. capacitors 42-44) will need to be different from the values that they would have had if there had been direct electrical connection to the dies 14 and 15.

It will be appreciated that a capacitative coupling 28 may differ from that of figures 3 and 4 in various ways while remaining within the scope of the invention.

For example the plates 50 and 60 may be of different materials, for example copper or aluminium; there may be different numbers of plates 50 and 60; and they may be of different shapes and sizes.

Claims

- 11 - Claims 1. A process for making capsules, the process using films of

a water- soluble or digestible polymeric material, and the process comprising the steps of deforming the films to form a multiplicity of enclosures between a pair of rotary welding dies, filling the enclosures with a flowable filling material, welding the films together by dielectric welding at the rotary welding dies to form a multiplicity of enclosures containing the filling material, wherein radio frequency signals are coupled to at least one of the rotary dies through a respective multi-plate capacitor, the capacitor comprising a multiplicity of spaced-apart parallel flat plates arranged to rotate with the die, and a multiplicity of non-rotating plates interleaved between them.
2. An apparatus for making capsules, using films of a water-soluble or digestible polymeric material, the apparatus comprising a pair of rotary welding dies defining recesses, means to feed the films between the dies, the films deforming into the recesses so as to define enclosures, means to fill the enclosures with a flowable filling material, and means to couple radio frequency signals to the rotary welding dies so that the films undergo dielectric welding to form a multiplicity of enclosures containing the filling material, wherein radio frequency signals are coupled to at least one of the rotary dies through a respective multi- plate capacitor, the capacitor comprising a multiplicity of spaced-apart parallel flat plates arranged to rotate with the die, and a multiplicity of non-rotating plates interleaved between them.
3. An apparatus as claimed in claim 2 wherein the - 12 - capacitor plates that rotate with the die are circular or annular.
4. An apparatus as claimed in claim 1 or claim 2 wherein the capacitor plates that rotate with the die are at a separation of between 1 and 3 mm.
5. An apparatus as claimed in any one of claims 2 to 4 wherein the rotating plates and the non-rotating plates are separated only by air.
6. An apparatus as claimed in any one of claims 2 to 5 wherein the area of overlap between the rotating plates and the non-rotating plates is adjustable.
7. An apparatus as claimed in any one of claims 2 to 6 wherein the radio frequency signals are coupled to both of the rotary dies through respective multi-plate capacitors.
8. An apparatus for making capsules substantially as hereinbefore described with reference to, and as shown in, figure 1, 2, 3 and 4 of the accompanying drawings.