EP3326932B1

EP3326932B1 - Closure system for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products

Info

Publication number: EP3326932B1
Application number: EP17194211.3A
Authority: EP
Inventors: Marco Maria Carlo RIZZARDI; Giuseppe ADDABBO
Original assignee: Capsulit SpA
Current assignee: Capsulit SpA
Priority date: 2016-11-24
Filing date: 2017-09-29
Publication date: 2019-09-11
Anticipated expiration: 2037-09-29
Also published as: IT201600119044A1; EP3326932A1; ES2761354T3

Description

The present invention relates to a closure system for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products.
Bottles or vials containing pharmaceutical products such as lyophilized or liquid products for injection or perfusion are generally closed by means of a perforable rubber plug, for example by means of a needle, held on the neck of the bottle by means of an aluminium capsule that completely covers the rubber plug. The aluminium capsules generally have a portion that may be removed by tearing, which allows access to the rubber plug.
The main drawback of aluminium capsules consists in the fact that the steps of mounting the capsule on the rubber plug and on the neck of the bottle cannot be executed in conditions of sterilisation and the absence of undesired particles because the folding and cutting operations of the aluminium sheets for making the capsules and the mounting thereof on the mouth of the bottle involve the generation of aluminium powders which are incompatible with the conditions of sterilisation and the absence of undesired particles required for the type of products contained in the bottle itself. Such aluminium capsules make it therefore difficult to minimise the level of particle contamination admitted into controlled-atmosphere environments, such as a cleanroom.
Another drawback of aluminium capsules consists in the fact that the operator who removes the removable portion risks being injured with the sharp edges of the aluminium sheet.
On the other hand, also the use of capsules made of materials of the
plastic type are not free from drawbacks. Such a capsule is disclosed in WO97/31839 .
In particular, capsules made of plastic often are not capable of supporting the temperatures that can be reached in autoclave sterilisation processes, which may reach up to 140°C, or in any case they undergo deformations such as to put at risk the sterilisation conditions of the bottle itself. In order to resist the sterilisation processes, the plastic capsules must have more rigid structures that require a significant force of application in order to be mounted securely on the neck of the bottle, which force of application cannot generally be obtained with normal capsuling machines. The implementation of capsuling machines with increased force of application results in a significant increase of the set-up costs of the processing plant. Moreover, the use of an increased force could result in problems of the bottles or the capsules themselves breaking.
Plastic capsules are also known that have several and numerous components mutually assembled with one another in various operations which however, on the one hand do not ensure an adequate resistance to the autoclave sterilisation, and on the other hand, result in an apparent increase of the production and assembly times and costs of the capsule itself.
It is the object of the present invention to make a closure system for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products, that is easier to make and mount on bottles, and therefore is more economically competitive when compared to the known technique, and in particular to the plastic capsule.
It is another object of the present invention to make a closure system for bottles that does not result in the formation of powder during the mounting on the bottles.
It is another object of the present invention to make a closure system that is capable of providing the amplest guarantees of reliability and safety in use.
It is another object of the present invention to make a closure system that allows the bottle to be subjected to autoclave sterilisation procedures.
These objects according to the present invention are achieved by making a closure system for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products, as disclosed in claim 1.
Further features are provided in the dependent claims.
Further features and advantages shall be more apparent from the description of two preferred, but not exclusive, embodiments of a closure system for bottles, illustrated as an example and not for limiting purposes with reference to the accompanying drawings, in which:

figure 1 is a front view of a bottle provided with a first embodiment of a closure system, according to the invention;
figure 2 is a perspective view of the outer capsule of the closure system illustrated in figure 1, according to the invention;
figure 3 is a perspective view of the inner capsule of the closure system illustrated in figure 1;
figure 4 is a front sectional view of the closure system of figure 1, according to the invention;
figure 5 is a front sectional view of a variant of the closure system illustrated in figure 1, according to the invention;
figure 6 is a perspective view of a variant of the inner capsule of the closure system illustrated in figure 1 or in figure 7, according to the invention;
figure 7 is a front view of a bottle provided with a second embodiment of a closure system, according to the invention;
figure 8 is a perspective view of the outer capsule of the closure system illustrated in figure 7, according to the invention;
figure 9 is a front sectional view of the closure system of figure 7, according to the invention;
figure 10 is a front sectional view of a variant of the closure system illustrated in figure 7, according to the invention.

With reference to the mentioned drawings, the closure system for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products, indicated as a whole with reference number 1, comprises:

a perforable closure body 3 adapted to close the mouth 5 of a bottle 7;
an inner capsule 9, able to be fitted onto the neck 11 of the bottle 7, configured to hold the closure body 3 in a sealed closure configuration of the mouth 5 of the bottle 7, in which the inner capsule 9 comprises an opening 13 adapted for allowing access to the closure body 3;
an outer capsule 15, able to be fitted onto the inner capsule 9.

According to the invention, the outer capsule 15 is made in a single body and comprises an upper disc-shaped portion 17 configured to close the opening 13 of the inner capsule 9 and a lower portion 19 able to be fitted around the inner capsule 9. Moreover, according to the invention, the outer capsule 15 comprises a breaking line 21 between the upper disc-shaped portion 17 and the lower portion 19.
As shown in the accompanying drawings, advantageously the outer capsule 15 closes and covers the inner capsule 9 both at the top and at the sides.
Advantageously, the inner capsule 9 comprises, on its lateral surface, a plurality of through-openings 33.
Advantageously, the lower portion 19 of the outer capsule 15 is fitted around the inner capsule 9, and is fitted around the inner capsule 9 so as to completely cover the side thereof, and in particular the lateral through-openings 33.
Advantageously, the outer capsule 15 is fitted around the inner capsule 9 with interference so that the outer capsule 15 and the inner capsule 9 define a single body capable of giving resistance to the forces that develop, for example during the autoclave sterilisation.
Advantageously, the outer capsule 15 is made of a material of the plastic type through injection moulding.
Preferably, the outer capsule 15 is made of a material of the polypropylene type.
Advantageously, the breaking line 21 comprises a plurality of bridges 23 made through the aforesaid injection moulding.
In particular, the outer capsule 15 may be made in a single injection moulding step together also with the bridges 23.
Alternatively, or additionally, the breaking line 21 may comprise a weakened line defined by an incision, or partial cut, of the outer capsule 15 executed in a step successive to the one of the injection moulding of the outer capsule 15 itself.
The breaking line 21 allows easily separating the upper disc-shaped portion 17 of the outer capsule 15 from the lower portion 19 fitted around the inner capsule 9. This allows exposing the opening 13 of the inner capsule 9 and allows the access and perforation, for example by means of a needle, of the closure body 3.
The lower portion 19 of the outer capsule 15 may comprise, substantially at the breaking line 21, a band 25 having a radial thickness substantially less than the radial thickness of the remaining part of the lower portion 19.
Advantageously, as shown in the accompanying drawings, the lower portion 19 of the outer capsule 15 comprises, substantially at the breaking line 21, a band 25 having a radial thickness that narrows in the axial direction 27 of approach to the breaking line 21.
The reduction of the thickness of the wall of the outer capsule 15 at the breaking line 21 further facilitates the separation of the upper disc-shaped portion 17 from the lower portion 19.
In particular, the upper disc-shaped portion 17 may be raised upwards and pulled off from the lower portion 19 by acting with the fingertip on the lower perimeter edge 24 of the upper disc-shaped portion 17 itself, which edge 24 is exposed with respect to the lateral wall of the lower portion 19, due to the narrowing of the thickness thereof approaching the breaking line 21.
If the breaking line 21 were defined by a plurality of bridges 23, the rotation of the upper disc-shaped portion 17 with respect to the central axis 27 would produce the same separating effect of the upper disc-shaped portion 17 with respect to the lower portion 19 because it would cause the breaking of the bridges 23 themselves.
Advantageously, the inner capsule 9 comprises a plurality of elastically deformable tabs 29 projecting radially towards the inside of the inner capsule 9 itself. Such tabs 29 are configured to engage with the finish 31 of the bottle 7.
Advantageously, the tabs 29 are obtained at the through-openings 33 on the lateral surface of the inner capsule 9.
The tabs 29 are preferably equally distributed angularly around the central axis 27.
Advantageously, also the inner capsule 9 is made of a material of the plastic type, and preferably of the polycarbonate type, through injection moulding.
The through-openings 33 obtained at the tabs 29 allow facilitating the removal of the tabs 29 themselves from the injection mould.
Moreover, by engaging with the finish 31 of the bottle 7, the tabs 29 allow the inner capsule 9 to hold the closure body 3 in a sealed closure configuration against the mouth 5 of the bottle 7.
The fact that the tabs 29 are elastically deformable, also due to the presence of the through-openings 33, allows easily fitting the inner capsule 9 on the neck 11 of the bottle 7. Indeed, in step of pressure applying the inner capsule 9 onto the neck 11 of the bottle 7, the finish 31 exerts a force in horizontal direction on the tabs 29 themselves, which force deforms the tabs 29 radially outwards until they exceed the finish 31. Once they have exceeded the finish 31, the tabs 29 may return to their rest configuration projecting radially towards the inside of the inner capsule 9, in which configuration they engage at the bottom with the finish 31 of the bottle 7.
Advantageously, the portion of cylindrical wall 54 of the inner capsule 9 which lies at the bottom of the tabs 29 has an increased cross-section with respect to the cross-section of the overlying tabs 29. Thereby, the resistance is ensured to the forces which develop during the autoclave sterilisation.
Advantageously, the tabs 29 project radially towards the inside of the inner capsule 9 itself with an inclination which is less than or equal 30° with respect to the underlying portion of cylindrical wall 54, that is with respect to the vertical direction. Thereby, the resistance is further ensured to the forces which develop during the autoclave sterilisation. The closure body 3 may be a rubber gasket 30, as shown in figures 4 and 9, or a rubber plug 32 as shown in figures 5 and 10.
The rubber gasket 30 and the rubber plug 32 are advantageously held at the top against the mouth 5 of the bottle 7 by the inner capsule 9.
The rubber plug 32 also has a lower portion which is inserted, with interference, into the mouth 5 of the bottle 7.
Advantageously, the tabs 29 are adapted to hold the closure body 3 on the mouth 5 of the bottle 7, thus ensuring the seal of the liquid contained inside the bottle 7, also under the action of the internal pressure generated during the autoclave sterilisation treatment.
The lower portion 19 of the outer capsule 15 comprises at least one rib 35 projecting radially towards the inside of the outer capsule 15, configured to engage in a corresponding seat 37 obtained on the outer surface of the inner capsule 9.
Preferably, there are provided at least two ribs 35 and two corresponding seats 37.
Advantageously, the ribs 35 develop circumferentially around the whole lower portion 19 of the outer capsule 15, like the corresponding seats 37 develop circumferentially around the whole outer surface of the inner capsule 9.
Thereby, when the outer capsule 15 is fitted onto the inner capsule 9, the two components are firmly constrained to each other and define an assembly that can be handled as though it were a single body.
Advantageously, the inner capsule 9 may comprise a rib 45 projecting radially towards the inside of the capsule configured to hold, by interference, the closure body 3. Preferably, such rib 45 develops circumferentially around the whole inner capsule 9.
Due to the holding by interference of the closure body 3 by the inner capsule 9, the outer capsule 15, inner capsule 9 and closure body 3 assembly define an assembly that can be handled as though it were a single body.
As shown in figures 5 and 10, alternatively to the tabs 38, the disc-shaped upper portion 17 may comprise, at its face that faces the opening 13 of the inner capsule 9, a cylindrical wall 41 axially protruding towards the edge 39 of the opening 13 and configured to engage with such edge 39.
The cylindrical wall 41 ensures the centring of the disc-shaped upper portion 17 of the outer capsule 15 with respect to the edge 39 of the opening 13.
As shown instead in figures 4 and 9, the disc-shaped upper portion 17 of the outer capsule 15 may comprise, at its face facing the opening 13 of the inner capsule 9, a plurality of tabs 38 axially projecting towards the edge 39 of the opening 13 and configured to engage with such edge 39.
Advantageously, the tabs 38 are also folded around the edge 39 of the opening 13, for example in assembly step between the outer capsule 15 and the inner capsule 9.
The engagement of the tabs 38 of the outer capsule 15 with the edge 39 of the opening 13 of the inner capsule 9 further stabilizes the coupling between inner capsule 9 and outer capsule 15.
In particular, such coupling provides the upper disc-shaped portion 17 with increased resistance to the internal pressure that is generated in vertical direction in the bottle 7, and therefore increased resistance to the push that acts on the closure body 3 during the autoclave sterilisation treatment.
The presence of the tabs 38 or of the cylindrical wall 41 does not however prevent the separation of the upper disc-shaped portion 17 of the outer capsule 15 from the lower portion 19 because such tabs 38, or such cylindrical wall 41, are removed from the edge 39 of the opening 13 when the upper disc-shaped portion 17 of the outer capsule 15 is removed.
In the variant of inner capsule 9 illustrated in figure 6, there are advantageously provided a plurality of bodies 47 projecting axially and radially towards the inside of the capsule 9, which are configured to hold the closure body 3 in the inner capsule 9.
In the embodiment illustrated in figures 7 to 10, the closure system 1 comprises a tamper-evident ring 43 associated with the outer capsule 15. The tamper-evident ring 43 is advantageously associated with the lower edge of the outer capsule 15 by means of a plurality of bridges 49.
The tamper-evident ring 43 comprises advantageously an undercut 51 configured to engage with the lower edge 53 of the inner capsule 9.
The tamper-evident ring 43 serves the purposes of emphasizing any attempts to tamper with the closure system 1.
When the bottle 7 is used, the operator, or patient, lifts the edge 24 of the upper disc-shaped portion 17 of the outer capsule 15 with his/her fingertip, thus breaking any bridges 23 that join such upper portion to the lower portion 19 and removing the tabs 38, or the circular wall 41, from the edge 39 of the opening 13 of the inner capsule 9.
Thereby, the opening 13 of the inner capsule 9 is exposed and it is possible to perforate the closure body 3 with a needle at the opening 13 of the inner capsule 9 to introduce it into the mouth 5 of the bottle 7 in order to suck the liquid contained in the bottle 7.
The closure system object of the present invention has the advantage of being made completely of a material of the plastic type and of being pressure applied onto the bottles, without generating powders that are incompatible with the sterility requirements of the product contained in the bottle itself, as instead happens in the case of closure systems at least partially made of aluminium.
Another advantage of the invention consists in the fact that the outer capsule, inner capsule and closure body assembly may be applied as though they were a single body, in a single step, to the bottle, directly in the cleanroom, immediately after the filling of the bottle with the product required. The application of the aforesaid assembly may also be executed in completely automated manner.
Another advantage again of the invention consists in the fact that the tabs on the inner capsule on the one hand, allow the closure system to resist in a satisfactory manner to the stresses generated during the autoclave sterilisation process, and on the other hand, to be easily pressure applied to the neck of the bottle.
A further advantage of the closure system according to the invention consists in the fact of being made in a minimum number of pieces that are easy to assemble with one another, that is rubber outer capsule, inner capsule and closure body.
The fact that the number of separate components of the closure system is minimised makes both the production of the closure system and its assembly on the bottle more economical and quicker.
Another advantage again of the invention consists in the fact that the closure system has multiple elements that may emphasize possible tampering therewith, such as for example the bridges of the outer capsule or the bridges that connect the outer capsule to the tamper-evident ring.
The closure system thus conceived is susceptible to many modifications and variants, all falling within the invention; moreover, all the details can be replaced by technically equivalent elements. In practice, the materials used, as well as their sizes, can be of any type according to the technical requirements.

Claims

Closure system (1) for bottles containing lyophilized or liquid products, particularly injectable or perfusable pharmaceutical products, comprising:
- a perforable closure body (3) adapted for closing the mouth (5) of a bottle (7);

- an inner capsule (9), able to be fitted onto the neck (11) of said bottle (7), configured to hold said closure body (3) in a sealed closure configuration of said mouth (5) of said bottle (7), said inner capsule (9) comprising an opening (13) adapted for allowing access to said closure body (3);

- an outer capsule (15), able to be fitted onto said inner capsule (9);
wherein said outer capsule (15) is made in a single body and comprises an upper disc-shaped portion (17) configured to close said opening (13) of said inner capsule (9) and a lower portion (19) fitted around said inner capsule (9), said outer capsule (15) comprising a breaking line (21) between said upper disc-shaped portion (17) and said lower portion (19), characterised in that the lower portion (19) of the outer capsule (15) completely covers the side of the inner capsule (9).
Closure system (1), according to claim 1, characterised in that said outer capsule (15) is made of a material of the plastic type through injection moulding.
Closure system (1), according to claim 1 or 2, characterised in that said breaking line (21) comprises a plurality of bridges (23) made through said injection moulding.
Closure system (1), according to claim 1 or 2, characterised in that said breaking line (21) comprises a weakened line made through incision following said injection moulding.
Closure system (1), according to one or more of the previous claims, characterised in that said lower portion (19) of said outer capsule (15) comprises, substantially at said breaking line (21), a band (25) having a radial thickness substantially less than the radial thickness of the remaining part of said lower portion (19).
Closure system (1), according to one or more of the previous claims, characterised in that said lower portion (19) of said outer capsule (15) comprises, substantially at said breaking line (21), a band (25) having a radial thickness that narrows in the axial direction (27) of approach to said breaking line (21).
Closure system (1), according to one or more of the previous claims, characterised in that said inner capsule (9) comprises a plurality of elastically deformable tabs (29) projecting radially towards the inside of said inner capsule (9), said tabs (29) being configured to engage with the bottle finish (31) of said bottle (7), said tabs (29) being obtained at through-openings (33) present on the lateral surface of said inner capsule (9) .
Closure system (1), according to one or more of the previous claims, characterised in that said lower portion (19) of said outer capsule (15) comprises at least one rib (35) projecting radially towards the inside of said outer capsule (15) configured to engage in a corresponding seat (37) obtained on the outer surface of said inner capsule (9).
Closure system (1), according to one or more of the previous claims, characterised in that said disc-shaped upper portion (17) comprises, at its face that faces said opening (13) of said inner capsule (9), a cylindrical wall (41) projecting axially towards the edge (39) of said opening (13) and configured to engage with said edge (39).
Closure system (1), according to one or more of the previous claims, characterised in that said disc-shaped upper portion (17) comprises, at its face that faces said opening (13) of said inner capsule (9), a plurality of tabs (38) projecting axially towards the edge (39) of said opening (13) and configured to engage with said edge (39) and folded around said edge (39) of said opening (13).
Closure system (1), according to one or more of the previous claims, characterised in that a tamper-evident ring (43) is associated with said outer capsule (15) .