METHOD FOR THE PRODUCTION AND FILLING OF AN APPLICATION PACKAGE FOR A LIQUID PHARMACEUTICAL PRODUCT

Abstract

A method for the production and filling of an application package for a liquid pharmaceutical product. A thermoforming film of thermoplastics laminated together is heated in order to plasticize the film at least in partial areas. Plasticized areas are thermoformed in a mold in order to form a chamber for the liquid pharmaceutical product and a tube-shaped application duct opening into this chamber, with the chamber and duct being enclosed by a non-thermoformed, essentially flat bonding area of the film. The liquid pharmaceutical product is filled into the chamber. The chamber and the application duct are sealed by covering the thermoformed and filled thermoforming film with an essentially flat covering film that is bonded to the bonding area of the thermoforming film enclosing the chamber and the application duct. The thermoforming film is pressed by a forming die during thermoforming into the mold in at least a partial area of the application duct.

Claims

1. A method for the production and filling of an application package (1) for a liquid pharmaceutical product, comprising the following process steps: heating a thermoforming film (3) comprised of thermoplastics laminated together in order to plasticize the thermoforming film (3) at least in partial areas (19), thermoforming plasticized areas of the thermoforming film (3) in a mold (12) in order to form a chamber (2) for the liquid pharmaceutical product and a tube-shaped application duct (6) opening into this chamber (2), with the chamber (2) and the application duct (6) being enclosed by a non-thermoformed, essentially flat bonding area (5) of the thermoforming film (3), filling the liquid pharmaceutical product into the chamber (2) of the thermoformed thermoforming film (3), covering the thermoformed and filled thermoforming film (3) with an essentially flat covering film (4) in order to seal the chamber (2) and the application duct (6), and bonding the covering film (4) to the bonding area (5) of the thermoforming film (3) enclosing the chamber (2) and the application duct (6), wherein the thermoforming film (3) is pressed by a forming die (24) during thermoforming into the mold (12) in at least a partial area of the application duct (6).

2. The method as claimed in claim 1, further comprising Pressing the thermoforming film (3) by the forming die (24) into the mold (12) in a thermally plasticized state, and calibrating the thermoforming film (3) between the forming die (24) and the mold (12).

3. The method as claimed in claim 2, further comprising directly bonding the covering film (4) to the bonding area (5) of the thermoformed and filled thermoforming film (3) using thermal ring sealing (8).

4. The method as claimed in claim 3, further comprising placing a plate-shaped sealing tool (15) on the covering film (4) in the bonding area (5) and using a ring-shaped heated ring projection that projects beyond a supporting surface of the sealing tool (15) for the thermal ring sealing (8).

5. The method as claimed in claim 4, further comprising exposing the thermoforming film (3) or the covering film (4) or both to heat radiation in an area (9) during thermal ring sealing (8) located externally next to the ring projection so that the thermoforming film (3) and the covering film (4) adhere to each other essentially in a whole bonding area (5) outside the ring sealing (8).

6. The method as claimed in claim 5, further comprising using a sealing tool (15) that is provided with a thermally insulating material inside the ring projection, at least in an area that comes to rest over the chamber (2) and the application duct (6) during the thermal ring sealing.

7. The method as claimed in claim 1, further comprising thermoforming the plasticized areas of the thermoforming film (3) into the mold (12) using blast air, and heating the blast air at least in the area of the application duct (6).

8. The method as claimed in claim 1, further comprising heating the thermoforming film (3) using a contact heater (10, 11) before thermoforming, with essentially only those areas (19) of the thermoforming film (3) that are provided for forming the chamber (2) and the application duct (6) during thermoforming being heated for plasticization.

9. The method as claimed in claim 8, further comprising heating the thermoforming film (3) from both sides before thermoforming.

10. The method as claimed in claim 1, further comprising using exchangeable molds (12) in order to modify as needed a volume of the chamber (2) produced during thermoforming of the thermoforming film (3).

11. The method as claimed in claim 1, wherein a laminated composite film comprising a layer of polypropylene (PP) and a layer of an acrylonitrile/methyl acrylate (AMA) copolymer is used as the thermoforming film (3).

12. The method as claimed in claim 1, wherein a laminated composite film comprising a layer of polyethylene terephthalate (PET), a layer of aluminum, and a layer of an acrylonitrile/methyl acrylate (AMA) copolymer is used as a covering film (4).

13. The method as claimed in claim 1, further comprising simultaneously thermoforming a plurality of the application packages (1) into one and the same thermoforming film (3) and sealing the plurality of the application packages with the covering film (4) in a single working step, and punching out the thermoformed and filled areas of the thermoforming film (3) sealed with the covering film (4) in order to complete the application packages (1).

14. The method as claimed in claim 13, further comprising cooling the thermoformed and filled thermoforming film (3) bonded to the covering film (4) after the thermal ring sealing and before the punching out.

15. The method as claimed in claim 1, further comprising providing the application duct (6) in an end area with a predetermined breaking point (7) in order to form a tip that can be broken off or cut off.

16. The method as claimed in claim 1, further comprising packing the punched-out application package (1) in a secondary package configured as a blister pack.

17. The method as claimed in claim 16, wherein the secondary package is comprised of laminated composite films including at least one of a layer of polyethylene terephthalate (PET), a layer of polypropylene (PP), or a layer of polyethylene (PE).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] An exemplary embodiment of implementation of the method according to the invention is described and explained in greater detail with reference to the attached drawings. The figures are as follows:

[0031] FIGS. 1A-1C show an application package produced by a method according to the invention;

[0032] FIG. 2 shows a schematic diagram of the production of the application package of FIG. 1;

[0033] FIG. 3 shows a schematic top view of a heating plate;

[0034] FIG. 4 shows a schematic top view of a mold for thermoforming;

[0035] FIG. 5 shows a schematic top view of a blowing plate for thermoforming;

[0036] FIGS. 6A-6D show the application package of FIGS. 1A-1C in various sizes; and

[0037] FIG. 7A and 7B show three application packages of FIGS. 1A-1C that are packaged in a secondary package.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] The application package 1 for an antiparasitic in a liquid active agent solution shown in FIG. 1A in a side view, in FIG. 1B in a bottom view, and in FIG. 1C in a top view is composed of a thermoforming film 3 and a covering film 4, with the thermoforming film 3 as a molded part forming a chamber 2 for the liquid pharmaceutical product and a tube-shaped application duct 6 opening into this chamber 2. The chamber 2 and the application duct 6 are enclosed by an essentially flat bonding area 5 of the thermoforming film 3. The covering film 4 covers the chamber 2 and the application duct 6 from the top and is bonded in the bonding area 5 of the thermoforming film 3 to said film. Bonding was carried out by thermal ring sealing, so that a ring sealing 8 surrounding the chamber 2 and the application duct 6 is visible in the top view (FIG. 1C). In sealing the covering film 4 onto the thermoforming film 3, the area 9 outside the ring sealing 8 was exposed to heat radiation in order to cause the covering film 4 to adhere to the thermoforming film 3 in said area as well. Finally, the application duct 6 is provided in an end area with a slot or a groove 7, which forms a predetermined breaking point at which the tip of the application duct 6 can be broken off in order to open the application package 1 for use.

[0039] FIG. 2 shows a schematic view of the most important stations in production of the application package 1 shown in FIG. 1. First, the thermoforming film 3 is pulled off by a first roller 17 and fed synchronously through a heating station with an upper heating plate 10 and a lower heating plate 11. Here, the thermoforming film 3 is heated until it plasticizes in those areas that are later to be formed. In this case, the upper heating plate 10 and the lower heating plate 11 can be adjusted separately in order to produce different temperatures for the upper side and lower side of the thermoforming film 3. This is because in the present exemplary embodiment, the thermoforming film 3 is a laminated composite film with a layer of polypropylene (PP) having a thickness of approx. 200 μm and a layer of Barex® having a thickness of approx. 350 μm. As the temperature range in which the Barex® layer is plasticized is typically around 80° C., while the temperature range in which the layer of polypropylene is plasticized is typically around 150° C., the upper and lower heating plates 10, 11 are set to these temperature ranges separately from each other.

[0040] After passing through the heating station, the thermoforming film 3 is fed to a thermoforming station with a mold 12 and a blowing plate 13. The mold 12 has a plurality of recesses in which the plasticized areas of the thermoforming film 3 are formed or thermoformed in the mold 12 by means of blast air from the blowing plate 13 and suction.

[0041] In the next cycle of the production process, the product from the thermoforming station is positioned below a dosing device 14, indicated here only by broken lines, which fills the liquid pharmaceutical product into the chamber 2 and the application duct 6 that were formed in the thermoforming film 3.

[0042] After filling of the thermoformed areas of the thermoforming film 3 in the dosing device 14, the covering film 4 is pulled off by a second roller 18 and placed on the thermoforming film 3. In a sealing station composed of a sealing plate 15 and a counterplate 16, the covering film 4 is sealed onto the thermoforming film 3, specifically by means of thermal ring sealing.

[0043] After a punching process (not shown here) in which the individual application packages 1 are punched out, the application package is in the form shown in FIGS. 1A-1C.

[0044] Also not shown in FIG. 2 is a device for producing the slot or groove 7 as a predetermined breaking point. This device is positioned upstream from the upper heating plate 10 and the lower heating plate 11, as the thermoforming film 3 is provided with corresponding slots prior to heating in the heating station, which later forms the predetermined breaking point in the application duct 6 of the formed application package 1. For this purpose, the PP layer is cut through and the Barex® layer is weakened.

[0045] FIG. 3 shows a schematic top view of the upper heating plate 10 of the heating station shown in FIG. 2. As shown in FIG. 3, the upper heating plate 10 is equipped with a number of partial areas 19 in which the upper heating plate 10 comes into contact with the thermoforming film 3. After this, the thermoforming film 3 is plasticized by contact heating only in the partial areas 19 that are to be finally molded in the thermoforming station. The areas of the thermoforming film 3 outside of the partial areas 19 are not heated to a sufficient degree to cause plasticization.

[0046] The heating station is comprised of the upper heating plate 10 shown here and the lower heating plate 11 shown by way of example in FIG. 2. In designing the heating surface contours, the two plates are configured congruently so that only the areas of the thermoforming film 3 that are to be deformed are plasticized in the heating station.

[0047] FIG. 4 is a schematic top view of the mold 12 for thermoforming of the chamber 2 and the application duct 6 of the application package 1. The broken lines indicate venting ducts 20 that allow the thermoforming film 3 to be completely molded in recesses 21 for forming the chamber 2 and the application duct 6.

[0048] FIG. 5 shows a schematic top view of the counterpart to the mold 12; this is a blowing plate 13. In the areas of the blowing plate 13 that come to rest over the chamber 2 and application duct 6 to be molded in the thermoforming film 3, pressure relief chambers 22 with blow openings 23 can be seen.

[0049] According to the present invention, the blowing plate 13 is also equipped with forming dies 24 that are movable with respect to the blowing plate 13 and can be moved out of said plate in order to press the thermoforming film 3 into the mold 12, thus pre-stretching it.

[0050] FIGS. 6A through 6D show application packages 1 of different sizes; the application package shown in FIGS. 6A and 6B is filled with a greater amount of pharmaceutical active agent solution than the application package 1 shown in FIGS. 6C and 6D, e.g. for use of an antiparasitic for large and small dogs.

[0051] As can be clearly seen, the two application packages 1 cannot be distinguished in the top view in FIGS. 6A and 6C; it only becomes clear from the side views of FIGS. 6B and 6D that the chamber 2 has different volumes. This is achieved according to the present invention by using interchangeable molds 12 that optionally lead to a chamber 2 having a reduced volume shown in FIGS. 6C and 6D or to a chamber 2 having a larger volume shown in FIGS. 6A and 6B. With the exception of the dosing device 14, further modifications need not be carried out in the system in which the method according to the invention is carried out in order to produce the different sizes of the application package 1 shown here.

[0052] Finally, FIGS. 7A and 7B show a side view and a top view of a sales unit with three application packages 1, which are packed in a secondary package 25 configured as a blister pack. This secondary package is comprised of a thermoformed blister film 26 with three blister-containing areas 27 for the application packages 1. The blister-containing areas 27 are sealed with a peelable blister covering film 28.

[0053] The thermoformed blister film 26 is comprised in this case of a PET/PP/PE laminate having a thickness of 350/100/75 μm. The peelable blister covering film 28 is composed of a PET/Al/PE laminate having a thickness of 12/12/50 μm.

[0054] The secondary package 25 has perforations 28 between the three blister-containing areas 27 at which the individual blister-containing areas 27 with the application packages 1 contained therein can be separated. In order to allow the individual application packages 1 to be torn off by hand, the secondary package 25 is provided with pre-cut areas 29 that can be torn off. To remove an application package 1, the blister covering film 28 is simply pulled off the thermoformed blister film 26 by hand.