WO1999043549A1

WO1999043549A1 - Method and apparatus for making a filled thermoplastic container by blow-moulding

Info

Publication number: WO1999043549A1
Application number: PCT/GB1999/000577
Authority: WO
Inventors: Martin M. Browne; John SANDØY
Original assignee: Nycomed Imaging AS
Current assignee: GE Healthcare AS
Priority date: 1998-02-25
Filing date: 1999-02-25
Publication date: 1999-09-02
Anticipated expiration: 2000-08-25
Also published as: GB9804005D0; AU2632699A; EP1058647A1; JP2002504447A

Abstract

A method of making a sealed container (1) of thermoplastic material containing a product (24) and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the method comprising blow moulding the container (1), and forming the outlet opening during such blow moulding with no mandrel or other member defining the inside wall of the outlet opening.

Description

METHOD AND APPARATUS FOR MAKING A FILLED THERMOPLASΗC CONTAINER BY BLOW-MOULDING

The invention relates to methods and apparatus for 5 making sealed containers from thermoplastic material and containing a product, and to the sealed containers.

It is known from EP-A-0 088 056 to provide unit dose containers of thermoplastic material containing a liquid for injection and closed by a non-resealable cap

10 which can be removed by breaking a frangible portion. Below the cap the neck of the container is formed as a female cone for sealingly receiving the male cone of a syringe, to enable the liquid to be withdrawn directly from the sterile conditions of the container directly

15 into a syringe. The male and female cones are formed to a standard size and conicity and the most widely accepted standard arrangement is known as a Luer fitting. Such fittings may additionally be provided with an arrangement for locking the syringe and the

20 container together, known as a Luer lock fitting, and comprising an outwardly directed flange on the outside of the neck for engagement with a screw thread provided on the syringe . The syringe can thus be screwed to the container to form the sealed connection. Luer lock

25 fittings are well known and an example of the use of such a fitting on a thermoplastic unit dose container is disclosed in WO 91/08729.

Thermoplastic unit dose containers are made using the known blow-fill-seal process. This basically

30 involves blow moulding the container, filling it with liquid and sealing the container before the thermoplastic material has hardened, all under sterile/ aseptic conditions. In the known process, a mandrel is lowered into the neck of the container and blow air is

35 introduced via an air passage in the mandrel. The liquid product is then introduced via a fill needle formed with another passage and during filling the blow - 2 - air is exhausted via the air passage. The outer surface of the mandrel at its tip defines a moulding surface to form the female cone where a male syringe cone will later be sealingly received. The outer surface of the mandrel also acts as a moulding surface to form the inside wall of the frangible portion where the cap is later to be broken away.

When the mandrel is lowered into the molten plastic there is a tendency for the plastic to stick to the mandrel, particularly to its leading edge. This causes the formation of an irregular lip or flange on the inside wall of the container neck, located at the leading edge of the mandrel. There is a risk of creating plastic threads and loose plastic particles. Plastic particles may also be generated by catching on the tip of the fill needle. Moreover, when the mandrel is lifted the plastic has cooled to a certain extent, so that there is abrasive movement between the mandrel and the inside wall of the container neck, further increasing the likelihood of plastic particle generation. This is particularly the case if deposits of plastic or fill product have built up on the mandrel over a period of time.

Viewed from one aspect the invention provides a method of making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the method comprising blow moulding the container, and forming the outlet opening during such blow moulding with no mandrel or other member defining the inside wall of the outlet opening.

Viewed from another aspect the invention provides a sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the container having no irregular internal flange or lip at or adjacent to the outlet opening.

Viewed from a further aspect the invention provides apparatus for making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the apparatus comprising means for blow moulding the container, and a mould for forming the outlet opening during blow moulding with no mandrel or other member defining the inside wall of the outlet opening. By avoiding contact between a mandrel or other member with the outlet opening which is later to receive a syringe cone or other equivalent device, the risk of plastic particle generation is minimised. The product contained by the container is preferably a liquid, but the container may also be used for containing a solid, for example in powder or tablet form, or a gas (in which case the gas itself may be used for the blow moulding step, rather than air) . In general, the product will be for medical use and is preferably a pharmaceutical product .

The volume of the product contained may be 1 ml to 1000 ml, preferably 1 ml to 500 ml, and most preferably 10 ml, 15 ml, 20 ml, 40 ml, 50 ml, 60 ml, 75 ml, 100 ml, 150 ml, 200 ml or 250 ml.

Product may be introduced into the container via a needle or the like passing through the outlet opening but not making contact therewith. Such an arrangement may be suitable for relatively small containers, for example containing less than 50 ml of product.

A further problem of the known blow-fill-seal process arises if it is desired to make a container with an outlet opening to fit a standard syringe cone and containing a liquid volume in excess of about 50 ml. The liquid has to be introduced very rapidly to avoid the plastic cooling and losing its ability to form the seal and the final shape of the container. For example, for a fill needle of 2.5 mm internal diameter introducing 50 ml of liquid in a 3 second fill time, the average liquid speed is 3.4 metres per second. The jet of liquid causes splashing, foaming and fog in the container during filling. The liquid tends to follow the exhaust air into the air passage and can build up and clog the passage. This can lead to problems such as fill volumes being not as specified, poor shaping of the container due to inadequate blow air in the next cycle, or dripping from the fill needle. A remedy would be to increase the cross-sectional area of the fill needle and of the blow/exhaust air passage, but this is not possible as the maximum size of the outlet opening is limited by its requirement to receive a male syringe cone of standard dimensions.

In a preferred method of the present invention, therefore, product is introduced into the container via an inlet opening separate from the outlet opening for receiving a syringe cone or other equivalent device. Thus the inlet opening dimensions can be chosen independently of the outlet opening. Such an improvement is of patentable significance in its own right .

Viewed from another aspect the invention provides a method of making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the method comprising blow moulding the container, and introducing liquid into the container via an inlet opening separate from the outlet opening.

Viewed from a further aspect the invention provides apparatus for making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the apparatus comprising means for blow moulding the container, and a mould arranged to form the outlet opening at a location separate from an inlet opening for introducing product into the container.

The arrangement of separate inlet and outlet openings is particularly useful for containers containing volumes of product of 60 ml or more, because the size of the inlet opening can generally be larger than in known designs. Viewed from another aspect, therefore, the invention provides a sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, wherein the container contains at least 60 ml of product. Preferably the container contains at least 70 ml or 75 ml or 80 ml or 90 ml or 100 ml or 150 ml or 200 ml or 250 ml or 1000 ml of product. It is expected that this aspect of the invention will be particularly useful for containers of 100 ml or more of product.

The outlet opening could be used during manufacture to introduce and exhaust blow air, with the inlet opening being used to introduce liquid. This could allow very rapid filling. In the presently preferred arrangement, however, the inlet opening is used both for introducing product to the container and for introducing and exhausting blow air.

The inlet opening may, for example, be formed in a shoulder of the container, adjacent to the outlet opening, or elsewhere. Preferably, product is introduced to the container through its base. If an inlet opening is provided in the container base, then the container may advantageously be formed and filled upside down. The main mould, defining the shape to which the main container body is blown, may thus also define the top parts of the container, such as the outlet opening and a removable cap. A mandrel for introducing blow air and product and for exhausting the blow air can then operate from above the upside down container.

After filling and removal of the mandrel the inlet opening will be sealed closed. This may for example be done by closing two halves of a head mould located above the main mould. The head mould may be heated to ensure a good seal. A nipple or other tooling markings showing that an inlet opening separate from the outlet opening has been used will generally be visible on the filled and sealed container. If a nipple is left on the container, it may for example be used as a means of hanging the container or for locking into a stand. A nipple could be arranged to be pressable inwardly of the container. For example the nipple could project into a concave recess at the base of the container, the concavity being sufficiently deep that the container is able to stand on its base .

The container may have a cap removable by breaking a frangible portion, to allow access to the outlet opening, the frangible portion being formed in conventional manner between a mandrel and the blow moulding tooling. However, this requires accurate positioning of the mandrel relative to the mould, usually within a tolerance of ± 0.1 mm. If the frangible portion is too thin this may cause leakage, and if it is too thick then it is difficult or impossible to remove the cap. Preferably, therefore, a frangible portion is formed during blow moulding with no mandrel or other member defining the inside wall of the frangible portion. Thus the frangible portion may simply be formed by being stretched over a rib on the mould external of the container. The thickness is then dependent on the thickness of the plastic before moulding (which will normally be extruded into the mould) and should consequently be more reliable. For the arrangement of separate inlet and outlet openings, the outlet opening could be formed by a mandrel, in the conventional manner, whilst avoiding the - 7 - problems caused by rapid filling through the outlet opening. Preferably, however, the outlet opening is formed during blow moulding with no mandrel or other member defining the inside wall of the outlet opening, to minimise the risk of plastic particle generation as discussed above.

The outlet opening could be blow moulded as a female cone. Preferably the outlet opening is formed as an annular inward projection for sealingly receiving the syringe cone or other equivalent device. The inward projection may define an orifice into which the syringe cone or other equivalent device can be inserted in sealing manner. Polypropylene and most other thermoplastics are strong and elastic and capable, when formed into an annular inward projection, of forming a good seal with a syringe cone or other equivalent device. The annular inward projection can be easily blow moulded, avoiding the use of a mandrel or the like, and thus minimise the risk of particle generation. An annular inward projection formed by blow moulding over a rib in the mould will tend to be thinned where the material is stretched over the rib.

In order to form a seal with a conic device, the minimum diameter of the outlet opening is preferably less than or equal to 10 mm. In the case of the container having a female cone, the minimum diameter will be the minimum diameter of the cone, whilst in the case of the container having an annular inward projection the minimum diameter will simply be the internal diameter of the orifice which it defines. A minimum diameter of the outlet opening of 10 mm or less will generally be suitable for a conic device in the form of a spike or a giving set . For standard Luer male syringe cones, the minimum diameter is preferably less than or equal to 4.3 mm, more preferably 3.8 mm.

If the outlet opening is formed as an annular inward projection, it is advantageously strengthened by - 8 - ribs. Viewed from another aspect, therefore, the invention provides a sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the container comprising an annular inward projection for sealingly receiving the syringe cone or other equivalent device, and a plurality of strengthening ribs arranged outwardly of the annular inward projection. In general, the ribs will be circumferentially spaced, e.g. two ribs 180° apart, and preferably extend longitudinally of the container neck.

Certain preferred embodiments of the invention will now be described by way of example and with reference to the accompanying drawings, in which:

Figure 1 is a front elevation of a container; Figure 2 is a side elevation of the container; Figure 3 is a cross-sectional of a container neck and cap, showing on the right hand side a view on lines III-III of Figure 2, and on the left hand side an equivalent view of a prior art container;

Figure 4 is a cross-sectional view of the container during manufacture;

Figure 5 is a cross-sectional view of the container at a later manufacturing stage;

Figure 6 is a cross-sectional view of the base of the container, with the base pushed in after moulding;

Figures 7a and 7b are respective elevation and cross-sectional views of a mandrel; Figures 8a and 8b are respective elevation and cross-sectional views of an alternative form of mandrel; and

Figures 9a and 9b are respective elevation and cross-sectional views of another form of mandrel. Figures 1 and 2 show a completed sealed container made of thermoplastic material. This comprises a main body 2 sealed closed by a cap 3 connected to a neck 4 by - 9 - a frangible portion 5. A twist off top 6 is connected to the cap 3 by a web 7 , and to the neck 4 by a pair of frangible webs 8. In use, when the twist off top 6 is turned relative to the container body 2 the cap 3 twists with the web 7. The frangible webs 8 and the frangible portion 5 tear to allow removal of the cap 3 and thus open the container. At the top of the container neck 4 a pair of outwardly directed lugs 9 are provided to engage in an internal thread channel of e.g. a syringe, ie. to provide a Luer lock fit.

Figure 3, on the right hand side, shows further details of the neck 4 and cap 3 arrangement. In particular, it will be noted that below the Luer lock lugs 9 the neck 4 is formed with an annular inward projection 10. The wall thickness of the projection is less than that above and below the projection. This thinning occurs during blow moulding as the plastic is stretched over a circumferentially extending rib of an outer mould defining the external shape of the container. The projection 10 is reinforced by a pair of opposed vertical ribs 11, defined by vertical grooves in the mould. The ribs are disposed radially outwardly of the projection. In use, once the cap has been removed by rupture of the frangible portion 5, a syringe cone or other equivalent device may be inserted into the neck to form a seal with the orifice formed by the projection 10.

The left hand side of Figure 3 shows the details of a known cap 3 and neck 4 configuration. It will be seen that the inner wall of the neck below the frangible portion 5 is formed as a female Luer cone for sealing engagement with a male syringe cone. The female cone is formed during manufacture between an outer mould member and a central mandrel, with the result that an irregular lip 12 forms at the lower end of the cone. It will also be noted that the frangible portion 5 in the known arrangement is formed in an annular space between the - 10 - outer mould and the inner mandrel, so that the positioning of the mandrel is critical to achieving the correct thickness of the frangible portion 5.

Figures 4 and 5 show the container 4 being moulded upside down in a blow-fill-seal machine. The mould tooling comprises a main mould 20 in two reciprocatable main mould parts 20a and 20b, a head mould 21 in two reciprocatable head mould parts 21a and 21b and a parison gripper 22 in two reciprocatable parts 22a and 22b. As shown in Figure 4, the parison gripper is in a closed position, gripping the parison, the head mould is in an open position and the main mould is in a closed position, defining the shape of the main body of the container. The lower end of the main mould defines the shape of the top part of the upside down container 1, including the neck 4, the cap 3 and the twist-off top 6 (as shown in Figures 1, 2 and 3) . No mandrel or other inner member is used to define the internal shape of the top part of the container. Figure 4 shows the container after its main part 2 and top part have been blown to the required shape by air introduced by a mandrel 23, and filled with liquid 24 also via the mandrel 23.

Figure 5 shows the manufacturing process at a later stage, after the mandrel 23 has been removed and the head mould 21 has been closed to seal the container. A nipple 25 is formed by the sealing process and this may be removed at a later process stage, or it could be left to serve as a hanger device or as a lock to fit into a stand. The container could be shaped to allow its base to be pushed in so that the nipple 25 is located in a recess 26, as shown in Figure 6. This allows the container to stand upright on its base, without the nipple 25 having to be removed.

Figures 7a, 7b, 8a, 8b, 9a and 9b, show various possible constructions of the mandrel 23. The mandrel of Figures 7a and 7b has a generally circular cross- section and is provided with a central passage 30 for - 11 - blow and exhaust air and, arranged radially outwardly of the central passage 30, a plurality (in this case four) liquid passages 31.

In the mandrel of Figures 8a and 8b, the passages are arranged in a line across a mandrel having a generally oblong cross-sectional shape. Air passage 30 is provided at one end of the oblong and a plurality of liquid passages 31 are provided at the other end. The separation of air passage 30 from liquid passages 31 is advantageous in that incoming liquid and exhaust air are separated, reducing the risk of clogging.

In the embodiment of Figures 9a and 9b, the mandrel is provided in two parts, a first mandrel part 23a having an air passage 30 and a second mandrel part 23b having a plurality of liquid passages 31. Again, the air and liquid passages are advantageously separated from each other.

It will be appreciated that the mandrel design is not constrained by having to form a female syringe cone and thus many variations are possible according to requirements .

Standard types of male syringe cone to which the containers described herein may make a sealing fit are Luer or Record cones. The female cones to which such male cones normally fit have respective conicities of

6:100 and 1:10. As mentioned previously, the containers described herein may equally be used to fit a spike or giving set or other equivalent fully or partly conic device .

Claims

- 12 - Claims

1. A method of making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the method comprising blow moulding the container, and forming the outlet opening during such blow moulding with no mandrel or other member defining the inside wall of the outlet opening.

2. A method as claimed in claim 1, comprising introducing product into the container via an inlet opening separate from the outlet opening.

3. A method of making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the method comprising blow moulding the container, and introducing liquid into the container via an inlet opening separate from the outlet opening.

4. A method as claimed in claim 3 , wherein the outlet opening is formed during blow moulding with no mandrel or other member defining the inside wall of the outlet opening .

5. A method as claimed in any preceding claim, wherein the outlet opening is formed as an annular inward projection for sealingly receiving the syringe cone.

6. A method as claimed in any preceding claim, wherein the container has a cap removable by breaking a frangible portion, to allow access to the outlet opening, wherein the frangible portion is formed during blow moulding, with no mandrel or other member defining - 13 - the inside wall of the frangible portion.

7. A method as claimed in any preceding claim, comprising introducing product into the container through its base.

8. A container containing a product, made by a method as claimed in any preceding claim.

9. A sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the container having no irregular internal flange or lip at or adjacent to the outlet opening.

10. A sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the container comprising an annular inward projection for sealingly receiving the syringe cone or other equivalent device, and a plurality of strengthening ribs arranged outwardly of the annular inward projection.

11. A sealed container of thermoplastic material having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, wherein the container contains at least 60 ml of product.

12. A sealed container as claimed in claim 11, wherein the container contains at least 100 ml of product.

13. Apparatus for making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe - 14 - cone, spike or giving set, or other equivalent fully or partly conic device, the apparatus comprising means for blow moulding the container, and a mould for forming the outlet opening during blow moulding with no mandrel or other member defining the inside wall of the outlet opening .

14. Apparatus for making a sealed container of thermoplastic material containing a product and having an outlet opening for sealingly receiving a syringe cone, spike or giving set, or other equivalent fully or partly conic device, the apparatus comprising means for blow moulding the container, and a mould arranged to form the outlet opening at a location separate from an inlet opening for introducing product into the container.