EP2651766B1 - Method for filling a cavity, in particular a blister of a blister packaging, with a liquid - Google Patents

Description

The invention relates to a method for filling at least one cavity, in particular a blister of a blister pack, with a liquid.

The filling of one or more cavities with substances, solid bodies or even liquids is known, for example, from the field of so-called visual packaging or blister packs. Blister packs are used in various industries and industries and are equipped with at least one cavity into which the content to be filled is received. In this case, the content recorded in the cavity or cavities is visible from the outside in a rule. Blister packs therefore have the advantage that they can be used as sales packaging.

In the pharmaceutical or medical field, blister packs are used for packaging pharmaceutical formulations, tablets, capsules or other forms of medicaments and for protecting them from environmental influences from the outside, which may possibly influence the pharmaceutical quality of the formulation.

Typical blister packs consist of at least two films, which in turn can be made up of several layers of different or the same materials. These are on the one hand a bottom layer or bottom foil, on the other hand a cover layer or cover foil.

In the bottom sheet, one or more trays may be formed, in which the pharmaceutical formulation, tablet or capsule is inserted or filled. The cover sheet is then placed on the bottom sheet and fixed to this, which can be done, for example, at the edge points by gluing, heat sealing, welding or the like. The films are usually made of plastic or metal (eg aluminum), with other materials, such as. B. paper can also be used in principle or in addition.

The DE 103 43 668 A1 shows a possible construction and a possible method for the production of a blister pack for pharmaceuticals. This is known in the art and it should therefore not be discussed in more detail.

From the FR 2 528 386 A1 a method for filling for filling a cavity according to the preamble of claim 1 is disclosed, wherein a first cavity is at least partially filled with liquid and at least a part of the liquid is displaced into a second cavity.

From the EP 2 243 715 A1 is a blister with at least two cavities are known, which are separated by a bridge element web-like. This makes it possible to arrange different drugs separately adjacent in the cavities and to remove simultaneously by pressure application.

From the DE 20 2007 003 050 U1 a blister pack is known, which is filled with a liquid or gel-like substance. In this case, the active ingredient should be released by diffusion to the environment. Possible applications are, for example, room deodorants or air fresheners, insect repellents, toilet deodorants. etc. It is mentioned in section 0004 of this document that a problem arises when the container is no longer completely filled after a certain period of use. The writing therefore obviously starts from a complete filling of the cavity of the blister pack with liquid or gel.

However, it will be apparent to those skilled in the art from the DE 20 2007 003 050 U1 , of the FR 2 528 386 A1 and the EP 2 243 715 A1 No guidance given how to accomplish a complete, in particular free of bubbles filling reliable. The solution to this problem is also not a task which the said writings have made and is not of further importance for the function of the inventions described in these documents.

However, there may well be applications in which a complete filling of a cavity with liquid, especially the blister (English = bubble) of a blister pack, with liquid is absolutely necessary. This case can occur, for example, when a blister pack is mounted on a medical-grade cartridge (for example a biosensor) and the reagent-filled liquid filled into the cavity of the blister pack should trigger a certain detection reaction at certain locations of the cartridge. The cartridge will usually contain a microfluidic system. So that a detection reaction aimed at by the liquid is not falsified or influenced, it may be necessary that after opening the cavity of the blister pack, for example by means of a Mechanism of the cartridge, the liquid is passed to the cartridge without air bubbles. In addition to other measures which may still have to be carried out technically in the mechanisms of the cartridge, this requires at least that the cavity of the blister pack itself is filled completely, ie without air bubbles, with liquid.

The invention is based on the object to provide a method which allows complete filling of a cavity, in particular a blister of a blister pack, with liquid.

This object is achieved with the features of claim 1.

• teilweise Befüllung einer Kavität eines zumindest zwei Kavitäten enthaltenen Halbzeugs mit der Flüssigkeit,
• zumindest bereichsweise Deckelung des Halbzeugs, derart, dass ein Austritt von Flüssigkeit aus dem Halbzeug ausgeschlossen wird,
• Verdrängung zumindest eines Teils der Flüssigkeit aus der bereits teilweise befüllten Kavität, derart, dass wenigstens eine andere Kavität durch einen Teil der verdrängten Flüssigkeit vollständig gefüllt wird und wenigstens ein anderer Teil der verdrängten Flüssigkeit zumindest teilweise wenigstens einen Überlauf füllt.

According to the invention, a method is provided for filling at least one cavity, in particular a blister of a blister pack, with a liquid which contains at least the following process steps:

• partially filling a cavity of a semi-finished product containing at least two cavities with the liquid,
• at least partially capping of the semifinished product, such that leakage of liquid from the semifinished product is excluded,
• Displacement of at least a portion of the liquid from the already partially filled cavity, such that at least one other cavity is completely filled by a part of the displaced liquid and at least another part of the displaced liquid at least partially fills at least one overflow.

By this method, a complete, bubble-free filling of at least one cavity is very reliable and reliable. So first only a first cavity needs to be partially filled with liquid, which is technically very easy. In addition, the partial filling has the advantage that the liquid during transport between corresponding stations of a manufacturing facility not so easily out of the partially filled cavity and can contaminate the environment or manufacturing facilities.

After the lidding of the semifinished product, for example the bottom foil of a blister pack, leakage of liquid is precluded. The semifinished product is thus already prepared for the subsequent processing step or "finished" and can be supplied promptly or at a later time the further process step of the above displacement. A storage or further transport is possible without risk of leakage of the liquid from the semifinished product.

The displacement of at least part of the liquid from the already partially filled cavity, which is carried out in a further method step, then leads to an interaction of the at least two cavities, so that ultimately a cavity is filled completely (without air inclusion). Due to the fluidic interaction of the cavities and the overflow, the cavity which is at first partially filled can be quasi referred to as a "filling cavity", and the at least one other, completely filled cavity can be referred to as a "functional cavity". The at least one overflow itself to be provided may, for example, also be a cavity in the manner of the other cavities be designed. This cavity, which receives a part of the displaced liquid and is at least partially filled, is then quasi called "overflow cavity". The "functional cavity" can be supplied to its destination or its intended function, for example in a medical-technical cartridge, according to further possible method steps to be described later.

It is very expedient to design the method such that the filling volume of the liquid in the first partially filled cavity is selected such that even with only partial displacement of this liquid from the first partially filled cavity that completely filled at least one other cavity and the at least one overflow is at least partially filled. In fact, it can not be ruled out that during the displacement of the liquid from the first partially filled cavity, it is not completely but only partially displaced so that a residual amount of liquid remains in the cavity, which is at first partially filled. Nevertheless, complete filling of the at least one other cavity and at least partial filling of the at least one overflow with excess liquid should be possible. For this purpose, as a rule, the volume of the cavity, which is at first partially filled, will also be chosen to be significantly larger than the volume of the cavity to be completely filled. The process reliability of the method according to the invention is thus increased.

A further advantageous embodiment of the inventive concept is that the lid of the semifinished product is such that an escape of liquid from the semifinished product is excluded and a liquid transport or liquid exchange between the cavities takes place only under application of a certain pressure. In this way, it is possible to store or transport the capped semifinished product without the liquid already filled into the first cavity arriving in another cavity prematurely, ie before further processing (displacement of the liquid from the already partially filled cavity). Although the person skilled in the art will anyway provide for a fluidic connection between the at least two cavities, this embodiment of the invention can further increase the process reliability since a liquid transport prematurely effected between the cavities could under some circumstances lead to impairment of this process Obtaining a liquid transport between the cavities is understandably by appropriate dimensioning (eg. Design of fluidic "valves" between the cavities) are dimensioned so that this only for a liquid transport between the cavities jedo ch does not lead to leakage of liquid from the semifinished product.

The displacement of at least part of the liquid from the already partially filled cavity can take place in different ways. For example, it is conceivable to suck out the liquid from the partially filled cavity by applying a negative pressure or to pump it out by applying an overpressure. However, it has proved to be very simple for the device-technical process structure, if the displacement is carried out by a deformation of the cavity. The deformation of the cavity can advantageously be effected by means of a stamp-like tool.

It has proven to be very expedient that, at least during the deformation of the cavity, the semifinished product is aligned substantially vertically with its surface extension, wherein the cavity to be deformed is positioned in relation to the at least one other cavity and the at least one overflow below. As a result, in the case of deformation, the air in the partially filled cavity can be pushed forward particularly easily upwards in front of the liquid column and escape through a suitable venting device.

Conveniently, a vent opening should be introduced into the lid of the semifinished product only immediately before the deformation of the cavity, so that before the process step of displacement (deformation) a maximum possible closure of the system can be ensured to the outside.

In a development of the invention, after the deformation of the cavity and the complete filling of the at least one other cavity, the at least one other cavity is closed in a liquid-tight manner and expediently separated from the other cavities or the overflow after the liquid-tight sealing of the cavity. The completely filled cavity ("functional cavity") is thus present as a transportable and storable end product and can be supplied at a given time to its intended location or its intended function.

Standard machines, for example for the production of blister packs, produce the cavities in films by deep drawing. It therefore offers an advantageous manner that the cavities have been introduced into the semifinished product by deep drawing. Thus, at least the production of the semifinished product can be carried out on inexpensive standard machines.

According to a further embodiment of the method, it is provided that holes are introduced into the semifinished product after thermoforming. Such holes may for example serve as positioning holes, for the case that individual, for example, in each case at least two cavities and at least one overflow contained semi-finished products are to be processed. However, they can also serve as transport holes if the semifinished product is designed, for example, as a continuous strip with many "single semifinished products" lined up next to one another (as mentioned above).

However, the invention relates not only to a process as described above but also to a semi-finished product which is particularly well suited for use in such a process.

According to the invention, the semifinished product is at least partially film-like and has at least two cavities with a first volume or a second volume, wherein the volumes are of different sizes.

Due to the film-like design of the semifinished product, the cavities can be produced very easily by deep drawing on standard machines, in particular those for blister packaging. The different size of the cavities is a necessary prerequisite for the effect of the displacement described with regard to the method according to the invention, namely complete filling of a cavity, to occur.

Experiments have shown that it is very expedient to form the volume of the first cavity in about 50 to about 150 percent, preferably in about 100 percent, greater than the volume of the at least one second cavity.

Furthermore, it is conceivable that a semifinished product is provided, which is already covered at least partially, such that an escape of liquid from the semifinished product is excluded and a liquid transport between the cavities is possible only under application of a certain pressure. Of course, this presupposes that the semi-finished product or the at least one first cavity is already partially filled with liquid. A semifinished product prepared in this way could, for example, have been supplied by a supplier or already manufactured and temporarily stored in its own company and would then only have to be forwarded to the further method steps. The height of such pressure to be applied could be predetermined, for example, by sizing suitable, valve-like interruptions of a channel-like region located between the cavities. This ensures that a liquid transport between the cavities does not occur unintentionally before carrying out the further process steps.

The semifinished product can advantageously be capped, for example, at least in regions such that at least one channel-like region remains between the cavities partially interrupted and the at least one second cavity is connected to at least one overflow.

Conveniently, the at least one overflow may be formed as a further cavity in the manner of the other cavities. In this case, the cavity acting as an overflow may already have been introduced into the semifinished product by deep drawing with the other cavities and it is appropriate to connect the further cavity to the cavity to be completely filled by means of at least one fluidic channel and to provide it with a vent. Of course, the at least one overflow can also be configured differently, for example, only channel-like, in which case a suitable venting would be provided in the channel-like overflow itself.

Fig. 1

eine prinziphafte Darstellung eines möglichen Halbzeugs in einer Querschnittsansicht,

Fig. 2

eine Ansicht des Halbzeugs gemäß Fig. 1 in der Draufsicht,

Fig. 3a bis f

eine prinziphafte Darstellung unterschiedlicher Verfahrensschritte gemäß einem bevorzugten Ausführungsbeispiel des erfindungsgemäßen Verfahrens, in einer Ansicht wie bei Fig.1,

Fig. 4

eine prinziphafte Draufsicht auf das in einem Verfahrensschritt des erfindungsgemäßen Verfahrens weiter verarbeitete Halbzeug und

Fig. 5

eine prinziphafte Draufsicht eines mit dem erfindungsgemäßen Verfahren hergestellten Endprodukts in Form einer Blisterverpackung mit einem vollständig befüllten Blister.

Further advantages and embodiments of the invention will become apparent from embodiments, which will be explained in more detail with the aid of the accompanying figures. Mean

Fig. 1

a schematic representation of a possible semifinished product in a cross-sectional view,

Fig. 2

a view of the semifinished product according to Fig. 1 in the plan view,

Fig. 3a to f

a schematic representation of different process steps according to a preferred embodiment of the method according to the invention, in a view as in Fig.1 .

Fig. 4

a schematic plan view of the further processed in a process step of the method according to the invention semifinished product and

Fig. 5

a principle plan view of an end product prepared by the process according to the invention in the form of a blister pack with a fully filled blister.

First, on the Fig. 1 and 2 Referenced. Therein, a foil-like semifinished product 1 designed as an endless strip can be seen, which has three cavities 10, 11 and 12 with a volume V1, V2 or V3 transversely to its longitudinal extent. The volume V1 of The first cavity 10 is approximately 50 to 150 percent, preferably approximately 100 percent larger than the volume V2 of the second cavity 11. The volume V3 of the third cavity 12, however, is merely to be selected such that the cavity 12 readily absorbs excess liquid F. can (see also Fig. 3d ). For example, the volume V3 of the cavity 12 may be selected to be approximately 40 to 60 percent, preferably approximately 50 percent smaller than the volume V2 of the second cavity 11.

According to the embodiment of the sheet-like semifinished product 1 as a continuous strip a plurality of successive areas with three cavities 10 to 12 or 10 'to 12', etc., can be seen. Along the outer edge regions of the endless strip also transport holes 13 can be seen. However, it would be conceivable to process the respective regions (indicated by dashed lines) as individual semi-finished products 1 ', 1 ", etc., wherein the holes 13 could function as positioning holes.

In the Fig. 3a to 3f Now, a preferred embodiment of a method according to the invention will be described in more detail. In this case, manufacturing facilities are only indicated insofar as they are conducive to the understanding of the invention.

In a first method step S1 ( Fig. 3a ), the first cavity 10 is filled with a liquid containing reagents F with a filling volume VB1, which is less than the volume V1 of this cavity. This results in a partial filling, so that an unfilled residual volume VR1 remains in the cavity 10. In this figure, the positioning or transport holes 13 are still indicated. The filling process was carried out from above and is not shown in detail because it is not essential for the understanding of the invention. It can be done with a suitable tool, for example with a pipette or the like.

In a further method step S2 ( Fig. 3b ) a cover sheet 2 is now placed on the semifinished product 1 and a first sealing tool 3 (indicated by dashed lines) brought vertically against the cover sheet 2. The sealing tool 3 takes into account a channel structure to be generated, which is based on Fig. 4 will be explained in more detail. It therefore has for this purpose recesses 30 and projections 31, which cause that only certain areas of the cover 2 are connected to the sheet-like semifinished product 1, others not. Thus, after the heat sealing between the cavities 10 and 11 or 11 and 12 channel-like, unsealed areas 21 and 21 '. In these channel-like, unsealed areas 21 and 21 ', the cover film 2 is thus only on the sheet-like semifinished product 1 and is not connected to this, so that in the areas 21 and 21' a Liquid transport or fluid passage can take place. It should be noted that the thickness of the cover 2 in the basic representations compared to the sheet-like semi-finished product 1 is exaggerated because of the better representability.

How out Fig. 4 As can be seen, a heat-sealed around the cavities 10 to 12 around a large area sealed area 20 (shown dotted), between the cavities 10 and 11 and 11 and 12, the channel-like, unsealed areas 21 and 21 'remain. Between the cavities 10 and 11, a sealed, web-like region 22 is additionally visible, which was achieved by the projection 31 of the sealing tool 3. This region 22 is dimensioned such that under normal circumstances (ie during transport and storage) a passage of liquid from the liquid F in the cavity 10 through the channel-like region 21 is not possible. Similarly, the large area sealed area 20 is a liquid-tight connection of the cover 2 with the sheet-like semifinished product 1. Only when increasing the pressure on the sealed, web-like region 22 (for example, by deformation of the first cavity 10, see also Fig. 3d ), the sealed, web-like region 22 can be broken. The area 22 thus acts as a sort of passage valve and can be dimensioned as needed.

The described capping of the semifinished product 1 with the covering film 2 and the desired liquid-tight connection can be effected by means of conventional methods such as heat-sealing, gluing, welding or the like.

In a further method step S3 ( Fig. 3c ) is now by means of a pin-like punching tool 4, a vent 14 in the cover 2, and indeed over the third cavity 12, introduced.

This is followed by a further method step S4 ( Fig. 3d ), in which the first cavity 10 is deformed by means of a punch-like tool 5. Specifically, the stamp-like tool 5 drives controlled by the cover 2 of the side facing away from the semifinished product 1 in the first cavity 10 a. Controlled means that by this retraction, the cavity 10 is not damaged, but only deformed. Due to the deformation of the cavity 10, a large part of the liquid F therein and also air is forced through the channel-like region 21 or in the direction of the sealed web-like region 22, whereby the region 22 is opened like a valve and the liquid F into the second cavity 11 arrived. It can be seen that, despite deformation of the first cavity 10, a filling residual volume VBR1 still remains in the first cavity 10, likewise a certain air entrapment L. Despite this, as a rule, not avoidable filling residual volume VBR1 of the first cavity 10, the second cavity 11 is filled with a filling volume VB2 to liquid F, which corresponds approximately to its volume V2. The second cavity 11 is thus filled completely (without air inclusion). As already mentioned, the first cavity 10 is significantly larger than the second cavity 11 in the exemplary embodiment and the selected filling volume VB1 of the first cavity 10 (in approximately 60 percent of the volume V1) corresponds approximately to 120 to 150 percent of the volume V2 of the second cavity 11. Such a dimensioning is sufficient, in addition to the complete filling of the cavity 11, to fill the third cavity 12 with a filling volume VB3, which is smaller than the volume V3 of the third cavity 12. This results in an unfilled residual volume VR3 of the third cavity 12 The third cavity 12 thus acts as an overflow for the second cavity 11 and can readily absorb the excess liquid F which can not be taken up by the cavity 11. The advancing in the displacement of the liquid F before the liquid front air can escape via the previously introduced vent opening 14.

It should be noted that in the Fig. 3d Although the surface orientation of the film-like semifinished product 1 is shown approximately horizontally, it has been shown in experiments that a substantially vertical orientation of the surface orientation of the film-like semifinished product 1 certainly offers advantages for the method step S4, the first cavity 10 being positioned at the bottom should. As a result, during the deformation of the cavity 10, the trapped air is very easily propelled up in front of the liquid front, breaking through the region 22 and reaching as far as the vent opening 14. In addition, the possible use of countersholders 6 is indicated by dashed lines.

It should be noted that although the third cavity 12 serves as an "overflow cavity" in the exemplary embodiment, the configuration of an overflow is not necessarily necessary in the manner of the cavity 12. The function of an overflow could already be effected by the channel-like region 21 'adjoining the second cavity 11 and provided with a corresponding vent opening. Other forms of overflow are conceivable. During the deformation, excess liquid F should be able to escape unhindered from the second cavity 11 into the overflow. However, the design of the overflow on the nature of the cavity 12 has the advantage that it can absorb a relatively large amount of excess liquid F and the risk of unwanted leakage of liquid F from the overflow to the outside (contamination / contamination of the environment) is avoided.

In a further method step S5 ( Fig. 3e ), that is, after a complete filling of the cavity 11 with liquid F has already succeeded, can be provided, a second Sealing tool 7 (indicated by dashed lines) in such a way to the cover sheet 2 and the film-like semifinished product 1 zoom in that the existing channel-like regions 21 and 21 'are closed again liquid-tight.

In a further method step S6 ( Fig. 3f ) can then be further provided to separate the completely filled with liquid F and finally sealed by sealing cavity 11 by means of a suitable cutting tool 8, ie to separate from the cavities 10 and 12. This can be done, for example, such that one in the Fig. 5 apparent, in plan view approximately square end product 9 is formed. The end product 9 in the exemplary embodiment is a single blister pack which has a cavity 11 (blister) completely filled with liquid. The cavity 11 is provided with a sealed area 20 'around it. Of course, the final product 9 may of course also have other manifestations, for example a plurality of completely filled cavities 11, 11 ', etc., if a correspondingly different separation took place in the upstream process steps.

As already mentioned, the end product 9 produced can be used later in a microfluidic or medical-technical cartridge, for example.

LIST OF REFERENCE NUMBERS

1, 1 ', 1 "

foil-like semi-finished product

10, 10 '

first cavity

11, 11 '

second cavity

12, 12 '

third cavity

13

Positioning or transport holes

14

vent

2

cover

20, 20 '

large area sealed area

21, 21 '

channel-like, unsealed areas

22

sealed, bar-like areas

3

first sealing tool

30

recesses

31

projections

4

punch

5

stamp-like tool

6

backstop

7

second sealing tool

8th

cutting tool

9

end product

V1

Volume of the first cavity

V2

Volume of the second cavity

V3

Volume of the third cavity

VB1

Filling volume of the first cavity

VB2

Filling volume of the second cavity

VB3

Filling volume of the third cavity

VBR1

Filling residual volume of the first cavity

VR1

unfilled residual volume of the first cavity

VR3

unfilled residual volume of the third cavity

L

air lock

S1-S6

steps

F

liquid

Claims (11)

1. Method for filling at least one cavity (11), particularly a blister of a blister packaging, with a liquid (F), comprising at least the following steps:

   - partly filling (S1) a cavity (10) of a semifinished product (1) containing at least two cavities (10, 11) with the liquid (F),

   - covering (S2) the semifinished product (1) at least in some areas, so as to prevent the escape of liquid (F) from the semifinished product (1),

   - displacing (S4) at least some of the liquid (F) from the already partially filled cavity (10),

   - characterised in that

   - at least one other cavity (11) is completely filled by a portion (VB2) of the displaced liquid and another portion (VB3) of the displaced liquid (F) at least partially fills at least one overflow (12).
2. Method according to Claim 1, characterised in that the fill volume (VB1) of the liquid (F) in the initially partially filled cavity (10) is chosen such that even if this liquid (F) is only partially displaced from the initially partially filled cavity (10), the at least one other cavity (11) is completely filled and the at least one overflow (12) is at least partially filled.
3. Method according to at least one of the preceding claims, characterised in that the covering (S2) of the semifinished product (1) is carried out such that liquid (F) is prevented from escaping from the semifinished product (1) and the transfer of liquid between the cavities (10 and 11) takes place only when a certain pressure is applied.
4. Method according to at least one of the preceding claims, characterised in that the displacement (S4) of at least some of the liquid (F) from the already partially filled cavity (10) is carried out by deformation of this cavity (10).
5. Method according to claim 4, characterised in that the deformation of the cavity (10) is carried out by means of a punch-like tool (5).
6. Method according to claim 5, characterised in that at least during the deformation of the cavity (10) the semifinished product (1) is aligned with its surface expanse substantially vertical, the cavity (10) that is to be deformed being positioned at the bottom in relation to the at least one other cavity (11) and the at least one overflow (12).
7. Method according to at least one of the preceding claims 5 or 6, characterised in that immediately before the deformation of the cavity (10) a vent opening (14) is formed in the cover (2) of the semifinished product (1).
8. Method according to at least one of the preceding claims 5 to 7, characterised in that after the deformation of the cavity (10) and the total filling (VB2) of the at least one other cavity (11) the at least one other cavity (11) is sealed off in fluidtight manner (S5).
9. Method according to at least one of the preceding claims 5 to 8, characterised in that after the cavity (11) has been sealed off (S5) in fluidtight manner it is separated from the other cavities (10, 12) or the overflow (12).
10. Method according to at least one of the preceding claims 5-9, characterised in that the cavities (10, 11, 12) have been formed in the semifinished product (1) by thermoforming.
11. Method according to at least one of the preceding claims 5-10, characterised in that after the thermoforming holes (13) are formed in the semifinished product (1).

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