METHOD OF FORMING AND FILLING A CONTAINER

Abstract: A method of forming and filling a container (10) with a liquid pharmaceutical product includes the steps of forming a container (10) from a suitable plastics material, the container having an open mouth; filling the container (10) with the liquid pharmaceutical product through the open mouth; sealing the open mouth with a seal (14) to form a sealed container (10); providing a recess (16) in the top (14); and securing in the recess a plug (18) of a suitable natural or synthetic rubber or plastics material, which material is adapted to permit the passage therethrough of a needle or the like and to seal again after withdrawal of the needle or the like.

Description: "METHOD OF FORMING AND FILLING A CONTAINER" BACKGRQIΓNP OF THE INVENTION This invention relates to a method of forming and filling a container with a liquid pharmaceutical product. Blow, fill and seal (BFS) technology is currently used in the pharmaceutical industry for the manufacture of flexible containers filled with sterile intravenous (TV) solutions. In terms of this technology, after a bottle has been blown, filled and sealed, a polyethylene/polypropylene cap with a rubberised polyethylene (PER) insert is welded onto the top of the bottle. This existing capping system satisfies the criteria for the safe administration and manipulation of sterile IV solutions, but the cap welding system, commonly termed mirror welding, is not completely efficient. The equipment for identifying defective welds is very expensive. The caps themselves and the cap welding equipment are also expensive. There is thus a need for an alternative method of providing sterile intravenous solutions in sealed containers. SUMMARY OF THE INVENTION According to a first aspect of the invention there is provided a method of forming and filling a container with a liquid pharmaceutical product, which method includes the steps of: (a) forming a container from a suitable plastics material, the container having an open mouth; (b) filling the container with the liquid pharmaceutical product through the open mouth; (c) sealing the open mouth with a seal to form a sealed container; (d) providing a recess in the sealed container; and (e) securing in the recess a plug of a suitable natural or synthetic rubber or plastics material, which material is adapted to permit the passage therethrough of a needle or the like and to seal again after withdrawal of the needle or the like. By a liquid pharmaceutical product, there is meant not only a pharmaceutical product for administration to humans, but also veterinary products for administration to animals. The product will generally be an intravenous solution. In step (a), the container, which is generally a bottle, may be formed by blow moulding. In step (b), the container is filled with the liquid pharmaceutical product by conventional means. In step (c), the open mouth is sealed with a seal to form a sealed container by conventional means. In step (d), the recess may be provided or formed in the seal for the open mouth of the container. Alternatively, the recess may be provided in the container and may be formed during step (a). The plug for location in the recess must have a shape and size, e.g the same shape and size, as the recess, so that it is a tight or close fit in the recess. In step (e), the plug may be secured in the recess by gluing or by being fused to the material of the container. For example, the plug may be made from a material which melts below 121 °C. Thus, when the container and the plug are passed through an autoclave to sterilise the container and contents, at 121 °C, the plug material melts and fuses to the material of the container to secure the plug in the recess. Alternatively, the plug may be glued or bonded into the recess using a suitable bonding agent such as for example ethyl vinyl acetate (EVA), either applied to the underside of the plug, for example by co-injection or coating, or utilised in the form of a wafer placed in the recess before the insertion of the plug. The EVA has a melting point of about 80 °C and thus melts during the autoclaving procedure to bond the plug to the bottle. As stated above, the plug must be made from a suitable natural or synthetic rubber or plastics material which is adapted to permit the passage therethrough of a needle and to seal again after withdrawal of the needle. The material is preferably a thermoplastic elastomer, for example a rubberised polyethylene. However, other materials are suitable for use. These materials should preferably possess the following properties: 1 food grade and preferably FDA approved; 2 soft, non-porous and easily pierceable by a hypodermic needle or the like without coring; 3 have a good memory, that is seal after removal of the needle or the like; and 4 ideally have the melting point below 121 °C. The container may also be provided with a dust cap, placed over the plug in the recess, and suitably secured to the container. For example, once the plug has been inserted into the recess, the plug may be held in place, prior to autoclaving or bonding, with a dust cap, for example a laminated polyethylene/nylon heat welded dust cap. This dust cap is removed at time of use to present a sterile surface for the administration of the pharmaceutical product in the container or for the addition of medicament via a needle to the pharmaceutical product in the container. According to a second aspect of the invention there is provided a combination of a container and a liquid pharmaceutical product in the container, the container being completely sealed, the sealed container including a recess, and a plug of a suitable natural or synthetic rubber or plastics material located in the recess and secured thereto, the plug material being adapted to permit the passage therethrough of a needle and to seal again after withdrawal of the needle. According to a third aspect of the invention there is provided a seal for use in sealing an open mouth of a container made from a suitable plastics material and adapted to be filled with a liquid pharmaceutical product through the open mouth, the seal including a recess adapted to receive a plug of a suitable natural or synthetic rubber or plastics material, which material is adapted to permit the passage therethrough of a needle or the like and to seal again after the withdrawal of the needle or the like. BRIEF DESCRIPTION OF THE DRAWTNOS Figure 1 is a schematic side view of a container of the invention having a first top; Figure 2 is a top view of the first top of the container of Figure 1 ; Figure 3 is a perspective view of a second top for the container of Figure 1; and Figure 4 is a schematic side view of the container of Figure 1 with the second top of Figure 3. DESCRIPTION OF EMBODIMENTS The invention will now be described in more detail with reference to the accompanying drawings. Referring to Figures 1 and 2 there is shown a container 10 which comprises a bottle 12 having a top or seal 14. The top 14 includes a recess 16 in which is located a plug 18. The plug 18 is covered with a dust cap 20. The container 10 is manufactured as follows. Firstly, the bottle 12 is blown, by conventional means, with an open mouth in the vicinity of the recess 16. Secondly, the container is filled with a liquid pharmaceutical product such as a sterile IV solution. Thirdly, the open mouth of the bottle 12 is sealed with a top or seal 14 which includes the recess 16, to form a completely sealed container 10. Fourthly, the plug 18 is located in the recess 16. Next, the dust cap 20, generally comprising a laminated polyethylene/nylon material, is heat welded over the plug 18 to hold it in position prior to secural in the recess 16. Next, the container 10 is autoclaved, firstly to sterilise the container and contents, and secondly to melt the material from which the plug 18 is made, so that the plug fuses to the recess 16. This fusion is necessary in order to secure the plug 18 in the recess 16, and to eliminate any air space between the plug 18 and the recess 16 which might harbour bacteria that could in turn be released when piercing the plug 18. As an alternative, a layer or a thin wafer of a suitable bonding material, for example ethyl vinyl acetate, may be located in the recess 16, whereafter the plug 18 is inserted. Then, again on autoclaving, the bonding material will melt to bond the plug 18 in the recess 16. The elimination of air between the plug 18 and the recess 16 is assisted by the convex design of the bottom of the recess 16 as illustrated. As stated above, the plug should be made from a material which is food grade and preferably FDA approved, which is soft, non-porous and easily pierceable by a hypodermic needle without coring, which has a good memory so that it seals after removal of the needle, and ideally which has a melting point below 121 °C. A suitable material is for example rubberised polyethylene. When it is desired to use the contents of the container 10, the dust cap 20 is removed, and a hypodermic needle or the like is pierced through the plug 18 and the material of the recess 16 and into the bottle 12. Thereafter the contents of the container 10 may be utilised or an additional medication may be added to the contents of the container 10. Referring to Figures 3 and 4 there is shown an alternative embodiment of the invention being a top or seal 30, for use on a bottle 12 of a container 10 as illustrated in Figure 1. The container 10 is manufactured as set out above and is filled with a liquid pharmaceutical product. Thereafter, the open mouth of the bottle 12 is sealed with the top or seal 30 which includes an elongate recess 32, to form a completely sealed container 10. The recess 32 includes a humped section 34 separating two flat sections 36, 38. A plug 40 which is of a shape and size to be a tight fit in the recess 32 is then located in the recess 32. The plug 40 may be secured in the recess 32 in any of the manners described above, for example by glueing the plug 40 into the recess 32. Next, a dust cap 42, generally comprising a laminated polyethylene/nylon material, is heat welded over the plug 40, to form a peripheral seal around the top 30. During this process, an indentation or other marking may be created in each portion of the plug 40 which is designed to fit on the flat sections 36, 38 of the recess 32, to indicate positions in which a needle may be inserted through the plug 40 into the bottle 12. The dust cap 42 may include a tab (not shown) to assist in peeling the dust cap 42 off the top 30, when it is desired to use the contents of the container 10. Next, the container 10 is autoclaved as described above. The plug 40 may be made from any of the materials discussed above. When it is desired to use the contents of the container 10, the dust cap 42 is peeled off, and a hypodermic needle or the like is pierced through the plug 40 in either of the regions of the plug 40 above the flat sections 36, 38, and thus through the material of the flat sections 36, 38 of the recess 32, and into the bottle 12. Thereafter the contents of the container 10 may be utilised or any additional medication may be added to the contents of the container 10. In a preferred feature of the invention, the dust cap 20, 42 is printed with instructions indicating the method of use of the container 10. This novel system for providing a container for a liquid pharmaceutical product has the advantage that it is cheaper to manufacture than conventional systems and yet is effective in use.

Claims: CLAIMS A method of forming and filling a container with a liquid pharmaceutical product, including the steps of : (a) forming a container from a suitable plastics material, the container having an open mouth; (b) filling the container with the liquid pharmaceutical product through the open mouth; (c) sealing the open mouth with a seal to form a sealed container; (d) providing a recess in the sealed container; and (e) securing in the recess a plug of a suitable natural or synthetic rubber or plastics material, which material is adapted to permit the passage therethrough of a needle or the like and to seal again after withdrawal of the needle or the like. A method according to claim 1 wherein in step (a), the container is formed by blow moulding. A method according to claim 1 or claim 2 wherein in step (d) the recess is provided in the seal for the open mouth of the container. A method according to any one of claims 1 to 3 wherein the plug has the same shape and size as the recess so that it is a tight fit in the recess. A method according to any one of claims 1 to 4 wherein in step (e) the plug is secured in the recess by gluing. A method according to claim 5 wherein the plug is secured in the recess using ethyl vinyl acetate either applied to the underside of the plug or utilised in the form of a wafer placed in the recess before the insertion of the plug. A method according to any one of claims 1 to 4 wherein in step (e) the plug is secured in the recess by being fused to the material of the container. A method according to claim 7 wherein the plug is made from a material which melts below 121 °C such that when the container and the plug are passed through an autoclave to sterilise the container and contents at 121 °C or higher, the plug material melts and fuses to the material of the container to secure the plug in the recess. A method according to any one of claims 1 to 8 wherein the plug is made from a thermoplastic elastomer. A method according to claim 9 wherein the thermoplastic elastomer is a rubberised polyethylene. A method according to any one of claims 1 to 10 which includes (f) securing a dust cap over the plug in the recess. A combination of a container and a liquid pharmaceutical product in the container, the container being completely sealed, the sealed container including a recess and a plug of a suitable natural or synthetic rubber or plastics material located in the recess and secured thereto, the plug material being adapted to permit the passage therethrough of a needle and to seal again after withdrawal of the needle. A combination according to claim 12 wherein the recess is provided in a seal for an open mouth of the container, through which the liquid pharmaceutical product is filled into the container. A combination according to either of claims 12 or 13 wherein the plug for location in the recess has the same shape and size as the recess so that it is a tight fit in the recess. A combination according to any one of claims 12 to 14 wherein the plug is secured in the recess by gluing. A combination according to claim 15 wherein the glue is ethyl vinyl acetate either applied to the underside of the plug or utilised in the form of a wafer placed in the recess before the insertion of the plug. A combination according to any one of claims 12 to 14 wherein the plug is secured in the recess by being fused to the material of the container. A combination according to claim 17 wherein the plug is made from a material which melts below 121 °C so that when the container and the plug are passed through an autoclave to sterilise the container and contents at 121 °C or higher, the plug material melts and fuses to the material of the container to secure the plug in the recess. A combination according to any one of claims 12 to 18 wherein the plug is made from a thermoplastic elastomer. A combination according to claim 19 wherein the thermoplastic elastomer is a rubberised polyethylene. A combination according to any one of claims 12 to 20 which includes a dust cap placed over the plug in the recess and suitably secured to the container. A seal for use in sealing an open mouth of a container made from a suitable plastics material and adapted to be filled with a liquid pharmaceutical product through the open mouth, the seal including a recess adapted to receive a plug of a suitable natural or synthetic rubber or plastics material, which material is adapted to permit the passage therethrough of a needle or the like and to seal again after the withdrawal of the needle or the like.

Inventors: STUART NEIL ARTHUR GORDON, STUART, NEIL, ARTHUR, GORDON
Applicants: CURTIS PHILIP ANTHONY, PHARMACARE LIMITED, STUART NEIL ARTHUR GORDON, CURTIS, PHILIP, ANTHONY, STUART, NEIL, ARTHUR, GORDON
Application year: 1998
Main classification: B65D51
IPC codes: A61J1, B65D51