WO2008007198A2

WO2008007198A2 - A method and apparatus for sealing containers

Info

Publication number: WO2008007198A2
Application number: PCT/IB2007/001909
Authority: WO
Inventors: Peter John Houzego; Bryan Keith Windus-Smith
Original assignee: Pfizer Limited
Priority date: 2006-07-10
Filing date: 2007-06-27
Publication date: 2008-01-17
Also published as: WO2008007198A3; JP2008019004A; TW200823110A; AR061849A1

Abstract

The invention relates to a platen (2) for use in the sealing of a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which includes a pocket slidably coupled to the disc, the platen comprising aperture regions corresponding to the apertures of the polymer disc and at least one ridge, wherein the aperture regions are free from ridges and the ridge (s) are spaced from the aperture regions. It further relates to a method of sealing a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which contains a pocket slidably coupled to the disc.

Description

A method and apparatus for sealing containers

The present invention relates to the sealing of containers. For example, it relates to the sealing of containers formed from polymer discs, wherein the container includes drug pockets containing a pharmaceutical formulation in powder form.

Adhering an aluminium foil laminate to a polymer container using heat and/or pressure is a well established method of sealing pharmaceutical packages against contamination from their external environment, for example, moisture penetration. The seal is achieved by melting a heat-seal polymer laminated to the aluminium foil into the polymer surface of the container and applying pressure so that the heat-seal polymer fuses with a molten or softened layer of the container, thus adhering the foil to the container. The quality of the seal depends upon the heat-seal polymer being well fused to the container over the whole of the sealing area.

Whilst the aluminium foil provides a substantially perfect moisture barrier, the heat-seal layer of the laminate, which is not entirely impervious to moisture penetration, provides a passage through which moisture can pass to reach the contents of the container, e.g. a drug product. Nevertheless, the moisture penetration through the heat-seal layer can be reduced to an acceptable level where the heat-seal layer is thin and the distance between the surface of the layer exposed to the environment and the contents is sufficiently long.

The seal may be formed using a hot roller or a hot flat platen. The temperature and contact time used is sufficient to melt the heat-seal layer and a thin layer of the contact surface of the container. The applied pressure then fuses the two molten layers together and causes the molten material to flow away from any high spots on the contact area until the entire sealing area is being pressed together. This ensures that a good seal is formed across the entire sealing area.

However, there are some problems associated with this known method. Firstly, the method is not suitable for use with all types of containers. Secondly, the thin layer of heat-seal polymer is unable to cope with relatively large deviations or imperfections in the finish of the container sealing surface, and thirdly, the integrity of the seal may be compromised by contamination (e.g. drug particles) on the sealing surface of the container or carried by the heat-seal layer of the laminate.

A type of container for which the above-described conventional sealing methods are not suitable is described in WO 03/015857, WO 03/066470 and WO 05/002654. Such containers comprise an annular disc in which a plurality of apertures have been formed through the disc such that the apertures form a circular array about the central axis of the disc. Each aperture houses a pocket which fits snugly within the aperture, whereby the pocket may be caused to move relative to the disc, out of the aperture. The pocket may contain a pharmaceutical formulation, including an active, in powder form. In order to protect the active, the disc includes a barrier layer on its top and bottom faces (i.e., the two major faces of the disc). In use, each pocket in sequence is urged out of the aperture, through the top barrier layer, whereby the powder formulation is exposed to a delivery apparatus.

In the above-described container, the pocket needs to slide relative to the disc to exit the aperture. Accordingly, the pocket must be free to move relative to the disc upon application of a force. In order for the pocket to move, the aperture should be free from the heat-seal polymer and it must be free from any distortion, as either may prevent or resist the pocket from exiting the disc.

It is an object of the present invention to address at least one of the above-mentioned problems.

According to a first aspect of the invention, there is provided a platen for use in the sealing of a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which includes a pocket slidably coupled to the disc, the platen comprising aperture regions corresponding to the apertures of the polymer disc and at least one ridge, wherein the aperture regions are free from ridges and the ridge(s) are spaced from the aperture regions.

The provision of a platen including one or more ridges and aperture regions devoid of ridges means that the area proximal to each aperture of the disc is not subject to pressure from the platen. Thus, even if the heat-seal layer of the barrier foil does melt in an area adjacent to the aperture, it is not pressed into contact with the aperture and as such, does not cause the heat-seal polymer to flow into the aperture and adhere the pocket to the aperture.

Additionally, polymer discs are typically formed by injection moulding, during which process, it is common for the polymer material to shrink on^' cooling, which leaves shallow depressions in the top and bottom surfaces. The use of a platen according to the invention overcomes the problem of sealing a barrier foil to a surface which includes such deformities.

Furthermore, should there be any contamination on the surface of the disc, e.g. drug powder, then the relatively high local pressure exerted by the ridge(s) causes flow of the heat-seal material and the disc polymer material away from the ridge(s) and this displaces the contamination from under the seal area, thus allowing a good seal to be achieved.

Still further, the ridge(s) being spaced from the aperture regions means that in use, the platen does not distort the apertures of the disc such that the pocket is not able to slide out of the aperture.

The term "barrier foil" should be construed as any sheet capable of being sealed to the disc surface which prevents or limits degradation of the disc contents by contact with an external environment. The barrier foil typically comprises a laminate including a heat-seal layer as an outer layer, the heat-seal layer comprising a heat-seal polymer which is activated by heat and acts td adhere the barrier foil to the disc. An example of a barrier foil includes a laminate of an aluminium layer and a heat-seal polymer layer. However, alternative metal foils or polymer sheets may be used in place of the aluminium layer. In addition, a multi-layer laminate may be used.

The term "slidably coupled" is used to define the relationship between the pocket and the aperture. The pocket is located within the aperture, but, upon application of a suitable force, the pocket is able to slide or move relative to the aperture such that the pocket exits the aperture. The aperture is defined by the disc material and is open at opposing ends, wherein the opposed open ends are closed by the barrier foil. Thus, the pocket may exit the aperture by being urged through the barrier foil at one of the open ends of the aperture.

In an embodiment of the invention, the platen is annular. An annular platen is able to conform to at least a portion of the disc with the minimum of material being used in the formation of the platen. This results in a platen which is easier to heat and which uses less energy to maintain a temperature which is higher than ambient temperature. It also reduces manufacturing costs.

The apertures of the disc may be arranged in a circular array, typically equally spaced from the central axis of the disc. Thus, the aperture regions of the platen may be arranged in a circular array in order to conform the aperture regions of the platen to the apertures of the disc.

In an embodiment of the invention as defined hereinabove, the platen includes at least one circumferential ridge. The ridge may be a single circular ridge; a single spiral ridge providing at least two ridge portions in a radial direction, i.e., the spiral includes at least two turns around the platen and thus provides adjacent ridge portions; or it may include two or more separate circular ridges or separate spiral ridges. The circumferential ridges are located between the aperture regions of the platen and the circumferential edge of the platen.

Moisture ingress into the drug pocket of the disc is typically via the heat-seal polymer layer. Thus, for a cylindrical disc, the only portion of the heat-seal polymer exposed to the external environment is at the circumferential edge of the disc. By providing at least one circumferential ridge on the platen, a good seal is obtained between the circumferential edge of the disc and the pockets within the apertures. This minimises moisture ingress via the heat-seal layer.

Optionally, the circumferential ridge(s) is/are arranged to define in use a gap between the outermost ridge and the edge of the disc. This avoids or reduces the risk of the edge of the disc being distorted during the sealing process. In some applications, it is important that the edge of the disc is free from distortions, particularly where accurate alignment of the disc is required.

In a further embodiment of the invention as defined anywhere hereinabove, the platen includes two or more circular ridges, or a spiral ridge having at least two complete turns about the platen, and a plurality of transverse ridges which bridge the adjacent circumferential ridges or ridge portions (in the case of a spiral ridge). The nature of the platen is such that, after sealing a disc, there may be areas between the seals formed by the ridges where a good seal has not been formed. In other words, there may be gaps formed between the barrier foil and the disc surface in areas corresponding to the gaps between ridges on the platen. Accordingly, any moisture that penetrates into this area would be free to move throughout the channel(s) formed by the gaps (i.e. between the adjacent sealed portions of the disc). The provision of transverse ridges which bridge the circumferential ridges or ridge portions on the platen therefore limits the connectivity of any channels formed between the circumferential seals and reduces moisture movement within these channels.

In a further embodiment of the invention as defined anywhere hereinabove, the platen includes at least one radial ridge which extends between adjacent aperture regions. The radial ridge prevents communication between the aperture regions and thus minimises the ability of moisture to travel from one pocket to neighbouring pockets.

In a still further embodiment of the invention as defined anywhere hereinabove, the platen includes at least one core ridge located between the aperture regions and the central axis of the platen. The core ridge(s) are similar to the circumferential ridge(s), but located inwardly of the aperture regions instead of outwardly of the aperture regions. Thus, the core ridge may be a single circular ridge; a single spiral ridge providing at least two ridge portions in a radial direction, i.e., the spiral includes at least two turns around the platen; or it may include two or more separate circular ridges or separate spiral ridges.

The core ridge(s) are useful for sealing discs which are annular in shape. As discussed above, a cylindrical disc only has one edge portion of the heat-seal polymer exposed to the external environment, whereas an annular disc has two edge portions exposed, namely the circumferential edge and the inner edge of the annulus. In order to limit or prevent moisture ingress to the pockets of the disc via the inner edge of the heat-seal layer, a platen including at least one core ridge as defined above can be used to create a good seal between the inner edge of the disc and the pockets.

In a yet further embodiment of the invention as defined anywhere hereinabove, the platen includes two or more circular core ridges or a spiral ridge including at least two turns of the disc to provide adjacent ridge portions, wherein adjacent core ridges or ridge portions are bridged by at least one bridging ridge.

As discussed above, the purpose of the bridging or transverse ridges are to limit communication between or along any channels that may have been formed between the seals made by adjacent core ridges.

In a further embodiment of the invention as defined anywhere hereinabove, the platen includes a plurality of aperture ridges, each of which encircles or surrounds a respective aperture region of the platen and is arranged to define a gap between the aperture region and the aperture ridge. The aperture ridges in use provide a good seal around the apertures and the drug pockets in the disc, this may further minimise moisture ingress into the drug pocket. The gap between the aperture ridge and the aperture region is needed to prevent distortion of the apertures in the disc during the sealing process when pressure is applied to the disc by the platen. Without the gap, some disc polymer material may be caused by the aperture ridge to flow into the aperture, thus preventing or resisting the pocket from slidably moving relative to the disc out of the aperture. The gap, therefore, may prevent distortion of the apertures within the disc by the aperture ridge when the platen is pressed into contact with the disc.

In a further embodiment of the invention as defined anywhere hereinabove, the ridge(s) of the platen include a contact region which is devoid of sharp edges. When sealing the barrier foil to the disc, the ridge(s) of the platen generate a relatively high local pressure which distorts the barrier foil. The absence of sharp edges on the contact region or portion of the ridge(s) reduces the likelihood of the barrier foil being ruptured during the sealing process.

The "contact region" of the ridge should be construed as that part of the ridge which is urged into contact with the barrier foil during the sealing process.

The contact region of the ridge(s) is typically the apex of the ridge and providing the apex of the ridge with a rounded profile, i.e. having a substantially constant radius, is an example of a ridge which is devoid of sharp edges.

As mentioned above, discs which are formed by injection moulding are subject to surface distortions during cooling. Such distortions may result in hollows and high spots being formed in the surface of the disc. Where the maximum height variation in the surface of the disc (i.e. the difference between the peak of the high spots and the trough of the hollows) is defined as h, the ridge(s) may have a height H (i.e. the maximum distance the ridge extends from the surface of the platen) such that the value of H/h is in the range 2 to 8. An embodiment of the invention may include ridge(s) where the H/h value is in the range 2.5 to 3.5. In other words, the height of the ridges may be selected to be 2 to 8 times (optionally 2.5 to 3.5 times) the maximum height variation of the disc to be sealed.

The H/h values of 2 to 8 ensure that a good seal can be achieved despite surface imperfections on the disc.

In a further embodiment of the invention as defined anywhere hereinabove, the platen includes a heat source which is capable of heating the platen to a temperature above an ambient temperature. The platen may further include a control mechanism for maintaining the platen at a predetermined elevated temperature.

A second aspect of the invention provides a method of sealing a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which contains a pocket slidably coupled to the disc, the method comprising: i. applying a barrier foil including an adhesive layer to the disc; and

ii. applying heat and pressure to areas of the barrier foil via a platen as defined above in the first aspect of the invention, wherein the applied heat and pressure are sufficient to seal the barrier foil to the disc.

The heat and pressure may be applied for a predetermined time, the time being sufficient to seal the barrier foil to the disc without distorting the disc or heating the interior of the pockets, as the contents of the pockets may be temperature-sensitive. Accordingly, the temperature and pressure are desirably applied for the minimum time possible to achieve a good seal. This time may be, for example, 0.1 to 3.0 seconds, more specifically, 0.3 to 1.0 second.

In a further embodiment of the invention as defined anywhere hereinabove, the pressure applied via the platen to the disc is 1 to 20 bar, more specifically 2 to 10 bar.

In a still further embodiment of the invention as defined anywhere hereinabove, the platen is heated to a temperature of 90 to 200⁰C. The temperature of the platen may be selected to be 125 to 15O⁰C. Most heat-seal polymers have a melting point between 90 and 200⁰C. Thus, a platen temperature of below 9O⁰C may be too low to melt the heat-seal polymer layer and above 200⁰C would risk damage to the disc or its contents and in any event would increase the operating costs with no benefit. Nevertheless, the choice of heat-seal polymer may result in lower temperatures being used or the need to use higher temperatures.

Unless otherwise stated, the above-described embodiments are not intended to be mutually exclusive. Accordingly, any two or more of the individual features described above in the embodiments of the invention together can be combined with the first or second aspects of the invention. Thus, the term "embodiment" used above should be construed as "an embodiment of the invention as defined in any preceding embodiment or aspect".

A specific embodiment of the invention will be described, by way of example only, with reference to the accompanying drawings in which:

Figure 1 is a top plan view of a platen according to the invention; Figure 2 is an enlarged view of an area of the platen shown in Figure 1 ; and Figure 3 is a cross sectional view through part of the platen shown in Figure 1.

Figure 1 shows an annular platen 2 having a circumferential edge 4 and an inner edge 6. The platen includes a plurality of aperture regions 8 arranged in a circular array about the axis of the platen. The aperture regions 8 are devoid of any ridges and are arranged to correspond to apertures of a disc to be sealed. Located between the aperture regions 8 and the circumferential edge 4 are four concentric circumferential ridges 10. The circumferential ridges are shown in cross section in Figure 3 and each has a diameter a of 0.5mm and a height b of 0.3mm, where the height is defined as the maximum distance the ridge extends outwardly from the surface of the piaten. As can be seen from Figure 3, the apex of the ridges 10,12,14,16,18,20 is rounded and has a substantially constant radius.

As shown in Figures 1 and 2, adjacent circumferential ridges 10 are joined by a number of radial ridges 12 which are arranged to be spaced circumferentially within the channel defined by the adjacent circumferential ridges 10. The portions of the circumferential ridges 10 which are proximal to the radial ridges 12 are reduced in width from 0.5mm to 0.4mm. This can be seen more clearly in Figure 2, where an arcuate recess 22 is formed in each of the circumferential ridges 10 at the point where the circumferential ridges 10 are joined by the radial ridge 12.

Located between the aperture regions 8 and the inner edge 6 of the platen 2 are four concentric core ridges 14. The core ridges 14 are arranged similarly to the circumferential ridges 10, wherein adjacent core ridges 14 are bridged by bridging ridges 18 at intervals within the channels defined by the adjacent core ridges 14.

Between each of the aperture regions 8 is a radial ridge 16 which extends from the outermost core ridge 14 to the innermost circumferential ridge 10 and dissects the land between the aperture regions 8.

Surrounding each of the aperture regions 8 is an aperture ridge 20. The aperture ridge 20 is spaced from the aperture region 8 by a distance which in use prevents or minimises distortion of the apertures of the disc during the sealing process.

The platen includes a heat source (not shown) which is common within the art and as such will not be described in more detail herein.

In use, the platen is used to seal an annular high density polyethylene (HDPE) disc. The HDPE disc includes a plurality of apertures arranged in a circular array about the central axis of the disc, wherein each aperture includes a drug pocket snugly retained therein. The drug pockets each contain a pharmaceutical formulation in powder form. The disc is formed by injection moulding and has surface height variations of 0.05 to 0.15mm. This provides an H/h (height of ridge/surface height variation of the disc) value of at least 2.

An aluminium foil laminate which includes a heat-seal polymer layer is placed over the disc and the platen described above with reference to Figures 1-3 is urged towards the disc. The platen is maintained at a temperature which is sufficient to melt both the heat-seal polymer of the laminate and the HDPE of the sealing surface of the disc. Upon contact of the ridges with the aluminium foil, the heat from the platen is transmitted through the aluminium layer to the heat-seal layer and the HDPE of the disc surface immediately below the ridge. The heat-seal layer and the HDPE polymer below the ridge both melt and the pressure from the platen forces the ridges into the disc surface, thus displacing the molten HDPE either side of the ridge.

The platen is urged towards the disc until the displaced HDPE has filled the channels between adjacent ridges. In other words, until the residual volume remaining in the channel defined by two adjacent ridges reaches zero. At this point, the ridges of the platen are prevented from penetrating further into the disc, as there is nowhere to which the displaced material can flow. A pressure senaor in the operating system of the platen detects this maximum penetration and the sealing process is halted.

Alternatively, the operating system of the platen may include a mechanical stop, which halts the sealing process when the ridges of the platen have penetrated to a predetermined depth.

The radius of the ridges and the selection of the sealing foil are such that the aluminium layer is not ruptured during the sealing process. The minimum radius of the ridge apex that can be used will depend upon the hardness of the aluminium contained within the foil laminate. A laminate including an annealed aluminium layer will allow a greater penetration into the disc surface and/or the use of a smaller radius of curvature for the ridges. It will also tolerate better any sharp edges on the ridges.

The spacing of the ridges from the aperture regions of the platen is sufficient that no distortion to the edges of the apertures in the disc occurs during sealing. The distortion may be limited to less than the height of the ridges.

The time for which the platen is in contact with the disc is selected such that the force required to displace the viscous molten materials is not sufficient to rupture the foil, but is not so long that the heat penetrates through the disc to the drug pockets, which contain the active drug product.

Typically, the contact time is 0.3 to 1.0 seconds, the pressure applied by the platen is 2 to 10 bar and the temperature of the platen is 130 to 150⁰C.

Tests have shown that the present invention provides a seal that has a moisture barrier performance which is equal to the moisture barrier performance achieved by a container which has a seal formed over the entire sealing area when the surface is flat and a conventional flat platen is used.

In addition, tests have shown that there was no degradation in seal quality when powder was present on the surface of the disc during the sealing process.

Claims

1. A platen for use in the sealing of a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which includes a pocket siidably coupled to the disc, the platen comprising aperture regions corresponding to the apertures of the polymer disc and at least one ridge, wherein the aperture regions are free from ridges and the ridge(s) are spaced from the aperture regions.

2. A platen according to Claim 1 , wherein the platen is annular.

3. A platen according to Claim 1 or Claim 2, wherein the aperture regions are arranged in a circular array about the central axis of the platen.

4. A platen according to any preceding claim, wherein the platen includes at least one circumferential ridge located between the aperture regions and the circumferential edge of the platen.

5. A platen according to Claim 4, wherein the platen includes two or more circumferential ridges and a plurality of transverse ridges which bridge adjacent circumferential ridges.

6. A platen according to any preceding claim, wherein the platen includes at least one radial ridge extending between adjacent aperture regions.

7. A platen according to any preceding claim, wherein the platen includes at least one core ridge located between the aperture regions and the central axis of the platen.

8. A platen according to Claim 7, wherein the platen includes two or more core ridges and adjacent core ridges are bridged by at least one bridging ridge.

9. A platen according to any preceding claim, wherein the platen includes aperture ridges each of which surrounds a respective aperture region and is arranged to define a gap between the aperture region and the aperture ridge.

10. A platen according to any preceding claim, wherein the ridge(s) include a contact region which is devoid of sharp edges.

11. A platen according to Claim 10, wherein the apex of each ridge has a rounded profile

12. A platen according to any preceding claim, wherein the ridge(s) have a height which is greater than the surface deformities of the polymer disc.

13. A platen according to any preceding claim, wherein the platen includes a heat source capable of heating the platen.

14. A platen according to Claim 13, wherein the platen includes a control mechanism to maintain it at a predetermined temperature

15. A method of sealing a barrier foil to a polymer disc, wherein the polymer disc includes a plurality of apertures, each of which contains a pocket slidably coupled to the disc, the method comprising:

i. applying a barrier foil including an adhesive layer to the disc; and i. applying heat and pressure to areas of the barrier foil via a platen as defined in any of Claims

1 to 12, wherein the applied heat and pressure are sufficient to seal the barrier foil to the disc.

16. A method according to Claim 15, wherein the method includes applying the heat and pressure for a predetermined time, the time being sufficient to seal the barrier foil to the disc but not to distort the disc or heat the interior of the pockets.

17. A method according to Claim 16, wherein the time is between 0.3 and 1.0 seconds.

18. A method according to any of Claims 15 to 17 where the pressure applied by the platen is 2 to 10 bar.