WO2009056605A1

WO2009056605A1 - Device for testing the push-through force on a blister strip and method therefor

Info

Publication number: WO2009056605A1
Application number: PCT/EP2008/064745
Authority: WO
Inventors: Stefan Lustenberger; Stephan Kurtze
Original assignee: Boehringer Ingelheim International Gmbh
Priority date: 2007-11-02
Filing date: 2008-10-30
Publication date: 2009-05-07
Also published as: DE102007052873A1

Abstract

A device for testing the push-through force (63) on a blister strip (50), wherein a bottom film (51) and a cover film (54) are peripherally connected to one another to implement multiple cavities (53) for a pharmaceutical agent formulation, comprises at least one column (11) having a traverse (12), which is disposed so it can be vertically displaced by a motor or hydraulically and which has a plunger (15), which acts on the blister strip (50), wherein the travel path thereof can be determined by way of at least one position pickup (13) and the force action thereof on the blister strip (50) can be determined by way of at least one force pickup (14). A mounting element (20) is provided to receive the blister strip (50), the mounting element comprising a baseplate (21) and opposing lateral guides (23), between which the blister strip (50) is received so it can be displaced horizontally, the blister strip lying on the baseplate (21) with the cover film (54) thereof.

Description

Device for testing the push-through force on a blister strip and method therefor

description

The invention relates to a device for testing the pushing force on a blister strip, in which for forming a plurality of cavities for a pharmaceutical drug formulation, a bottom sheet and a cover sheet are circumferentially connected to each other, with at least one column with a motor or hydraulic vertically displaceable arranged traverse with a on the blister strip acting stamp whose travel can be determined via at least one transducer and its force on the Blisterstrei- fen means of a force transducer. The invention further relates to a corresponding method,

As a rule, blister strips consist of a cover film and a bottom film, the cavities being formed in the bottom film. The cover film and the bottom film may be composed of one or more layers of different or the same materials. The cover sheet is sealed to the bottom sheet, for example by gluing, welding or sealing. The cover film and / or the bottom film are generally formed as metal and / or plastic and / or paper foil. These materials can be in multiple layers to be available. Typical metal foils include, for example, aluminum foils and aluminum composite foils made of aluminum and, for example, a plastic. The material used for the plastic films may be polyvinyl chloride (PVC), cycloolefin copolymer (COC), polychlorotrifluoroethylene (PCFE), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate (PC), polyester (UP), polyacrylate , Polyamide (PA) or other plastics. Often there is a blister strip of a cover foil made of aluminum, which closes the bottom foil for receiving the pharmaceutical product or active ingredient. This deep-drawn bottom sheet may also comprise an aluminum foil to prevent the entry of water into the cavity for receiving the pharmaceutical product. To create a further diffusion barrier or to increase the mechanical stability of the blister strip, optionally at least the aluminum foil of the cover foil can be covered on one or both sides with further plastic and / or paper foils.

In particular blister strips with the following layer sequence are frequently used. The cover sheet is made of aluminum and has a thickness of 10 to 80 microns, preferably from 20 to 50 microns, in particular from 30 to 40 microns. The cover sheet is sealed by means of a heat sealing lacquer to the bottom foil containing the cavities. The bottom sheets may alternatively consist of several layers, which materials may be the same or different. The bottom foil as a whole consists of the product-contacting side of a PVC, PP, PE layer or the like. with a thickness between 10 to 400 microns, preferably between 10 and 50 microns, in particular between 20 and 40 microns. This film may be bonded to an aluminum foil whose thickness is preferably 10 to 60 micrometers, advantageously 20 to 50 micrometers. The aluminum foil is followed by a polyamide film having a thickness between 10 and 40 micrometers, preferably 15 to 30 micrometers. In an alternative bottom sheet, the PVC sheet on the product-facing side is replaced by a polypropylene sheet or the like.

The bottom foil is made on the side facing the pharmaceutical product from a 30 micron thick PVC film, a subsequent 45 micron thick aluminum foil and an outside 20 micron thick polyamide film. In another blister strip, the cover sheet consists of a 38 micron thick aluminum foil and the heat sealing lacquer.

In some countries, provisions for the child-resistant packaging of medical products are being considered or already in place, in particular to make medicines that have a toxic effect or, if used improperly, a relatively high risk to health, difficult to access for children.

For the European market blister cards are used whose structure is described in the BfArm list or in DIN 55559. The blister cards are produced on a blister machine from an opaque PVC molding foil and an aluminum cover foil. The blister cards are divided by Langε- and transverse perforation into individual cavities. To remove the tablet, this is pushed through the cover sheet of the blister. Due to the material combination and the specific cross-perforation described in the BfArm list, the blister cards are considered child resistant.

For the American market, a blister card is used, which consists of a transparent PVC molding film and a so-called peel-push cover film, which is made up of several layers, for example aluminum / PET / paper (from inside to outside). The blister card is also cross-perforated by means of a longitudinal and transverse perforation and contains non-sealed areas at defined locations. To remove the tablets, a cavity is usually first separated in order to reach a grip tab (not sealed area) with which the paper / PET layer is pulled off. A transverse perforation is necessary so that the aluminum layer remains intact on the blister cavity during stripping. In particular, this perforation may be mounted at right angles to the direction of tear. Subsequently, the tablet is pressed through the aluminum layer. Due to the material combination and the design of the cross perforation or the ungeεiegelten areas the blister cards are considered child safe and / or senior friendly in accordance with CFR 16 part 1700.

The determination of the push-through force in the case of the blister strips or packages described above is becoming increasingly important with regard to the correct selection of the cover film.

There are known, for example, pressure / tension testing devices in the field of material testing, with which it is possible to carry out tensile and / or pressure measurements of, for example, opening and closing forces on packaging. Furthermore, For example, in the field of pharmaceutical packaging, it already carries out seal seam strength tests, tensile strength tests as well as flexibility and toughness studies of primary packaging.

A universal testing machine of this type is known, for example, from the company LLOYD INSTRUMENTS / AMETEK under the name LRX. Further testing machines of this kind offer u.a. also the company INSTRON. The ideal measuring range can be selected by using different force transducers. The travel speed of the traverse and the distance to travel are freely selectable within the specified limits of the machine. Such machines have corresponding end contact switches, which limit the Traversenweg up and down and stop the traverse, if necessary. The machine can be controlled either on the device itself or via a separate PC-based evaluation system (for example by means of the evaluation software NEXYGEN / ONDIO).

It is an object of the invention to provide a device of the type mentioned, can be performed reliably with the investigations of the pushing force on blister strips in a simple manner. It is a further object of the invention to provide a corresponding method.

According to the invention, the object with regard to the device is achieved in that a holder is provided for receiving the Blisterstreifenε, which consists of a base plate and opposite lateral guides, between which the blister strip is received horizontally displaceable, the blister strip with its cover sheet on the Base plate is located.

The object relating to the method is achieved according to the invention by inserting the blister strip with the cover film down into a holder consisting of a base plate and opposing lateral guides and then, by means of a stamp head attached to the stamp, forming the cavity of the bottom film formed as a cup in a recess the base plate is pressed until tearing of the cover sheet and in the moment of tearing the maximum force is determined as a pushing force.

Both the device and the method make it possible to quickly and above all reproducibly create a statement on the pushing force in blister strips, which makes it possible to select the appropriate cover film with regard to child safety and senior citizen friendliness. Furthermore, this supports a corresponding quality assurance system for the production of the blister strip.

In an advantageous embodiment of the device, the die has a spherical, in particular exchangeable, temple head, which acts on the cavity formed as a cup from the bottom foil. The ball shape of the stamp head simulates a force on the blister strip exerting fingers. Depending on the diameter of the stamp head, the finger of an adult or the finger of a child can be simulated on the one hand.

Preferably, the base plate in the region of the extension the axis of the punch with the punch head on a recess. Thus, when the cover sheet is torn during the test, the contents of the cavity, namely a tablet or capsule, fall into the recess.

According to a development, the guides are arranged laterally displaceable on the base plate and fixed at different distances from each other or to the center of the recess. Thereby, the distance of the guides to each other can be adapted to the respective width of the blister strip, whereby an optimal positioning of the cavity is achieved under the kopftempelkopf, which is particularly in view of the reproducibility of the results of advantage.

The guides expediently cover the blister strip at least regionally. A deflection of the Blister- εtreifens and thus a distortion of the result during the action of force is thus minimized. Furthermore, the blister strip is securely held in position during the application of force.

According to a development, the recess is formed as a bore or blind bore, the axis of which lies in the extension of the axis of the punch. The bore or boackbohrung can be easily manufactured and is advantageously variable in diameter by means of interchangeable inserts and consequently adapted to the diameter of the cavity formed as a cup.

In an advantageous embodiment of the method, the determination of the push-through force is carried out at central force and / or lateral force, wherein formed as a cup cavity of the bottom foil is completely or partially positioned under the punch head. In this case, the push-through force can have considerable differences depending on whether the force is applied centrally or laterally. Under both measuring conditions, a permissible range for the pushing force can be determined.

In order to achieve a high reproducibility, the determination of the push-through force is preferably carried out at a defined speed of the traverse with the punch

Expediently, during the course of the method, the travel path is recorded as elongation of the blister strip and the action of force, stored and displayed in a force-strain diagram. Thus, on the one hand, the result can be sufficiently documented and, on the other hand, simply the push-through force can be read off as the force at which the force abruptly drops as the distance or stretch increases.

It goes without saying that the features mentioned above and those yet to be explained below can be used not only in the respectively specified combination but also in other combinations. The scope of the invention is defined only by the claims.

The invention will be explained below with reference to an exemplary embodiment with reference to the accompanying drawings. It shows:

Fig.l is a schematic representation of the invention Contraption,

2 is a sectional view of the holder for the blister strip of FIG. 1,

3 is a representation of a force-strain diagram,

FIG. 4 shows a result representation of push through force measurements on different cover films, FIG.

The device 1 for checking the push-through force 63 on a blister strip 50 urafasst as main components at least one column 11 with a motor or hydraulically vertically displaceable arranged traverse 12 with a punch 15 with a punch head 16 which acts on the arranged under the punch 15 blister strip 50. The travel of the traverse 12 is determined by at least one position sensor 13. The force of the punch 15 on the blister strip 50 is transmitted by means of a force transducer 14, e.g. by means of load cells whose measuring range can be adapted to the measuring task by replacement. The signals of the transducer 13 and the force transducer 14 are fed to a PC-based evaluation system 30 and evaluated there with suitable software (for example, the software NEXYGEH / ONDIO) and the result is output via a printer 40.

For receiving the Bliεterstreifens 50, the device 1, a holder 20, which consists essentially of a base plate 21 and lateral guides 23. The blister strip 50 is arranged horizontally displaceable between the guides 23. Here, the blister strip 50 is located with its cover sheet 54 on the base plate 21 and the bottom sheet 51 shows with each formed as a cup 52 from the bottom sheet 51 cavities 53 with a tablet / capsule 55 as content in the direction of the punch 15, the punch head 16 is spherical. The diameter of the punch head 16 can be varied by replacing it with a correspondingly different punch head 16.

The base plate 21 is provided with a cavity 53 of the blister strip 50 associated recess 22 in the form of a bore or blind bore, whose axis coincides with the extension of the axis of the punch 15. The diameter of the recess 22 can be varied by means of corresponding change inserts. Ideally, the diameter of the recess 22 is slightly larger, in particular 1 to 2 mm, than the diameter of the cavity 53. The guides 23 are arranged laterally displaceable on the base plate 21 and fixed at different distances from each other or to the center of the recess 22, wherein the blister strip 50 is at least partially covered laterally by the guides 23.

To test the required push-through force 63, the cup 52 of the bottom foil 51 is pressed down into the recess 22 of the base plate 21 by means of the punch head 16 until the cover foil 54 tears open. At the moment of tearing the maximum force is determined. The test is carried out at a defined traversing speed of the traverse 12. During the test, the traverse path of the traverse 12 via the position transducer 13 and the force of the kopftempelkopfes 16 are fed to the blister strip 50 via the force transducer 14 of the evaluation unit 30 and over the printer 40 connected thereto is shown in a force-strain diagram 60 (FIG. 3).

In the force-elongation diagram 60, the force 61 as a function of the elongation 62 is shown. First, the elongation 62 increases gradually and then steeply until the cover sheet 54 breaks. At this moment, the maximum value for the force 61 is achieved, which corresponds to the push-through force 63. By evaluating a plurality of such diagrams, a corresponding statistic for the push-through force 63 can be determined.

FIG. 4 shows the results of various measurements for the push-through force 63 of five different cover film constructions 54.1 to 54.5. The measurement conditions for all measurements were as follows: 500 N load cell, travel speed 50 mm / s and 8 mm measuring path.

The first cover film structure 54.1 has the following structure from top to bottom: paper layer with a weight per unit area of 40 g / m², adhesive layer, aluminum layer (20 μm) and plastic film with a basis weight of 3.5 g / m². In the case of a central force 64, the push-through force 63 is about 83 N. With lateral force 65, the push-through force 63 is only about 59 N.

The second cover film structure 54.2 (from top to bottom: 12 μm PET, adhesive, 20 μm aluminum, plastic film) has a push-through force 63 of approximately 138 N or approximately 96 N. The third cover film structure 54.3 (from top to bottom: 15 μm PET, adhesive, 20 μm aluminum, plastic film) has a throughput pressing force 63 of about 155 N or about 107 N on. The fourth cover film structure 54.4 (from top to bottom: 6 μm PET, adhesive, 20 μm aluminum, plastic film) has a push-through force 63 of approximately 81 N or approximately 61 N. The fifth cover film structure 54.5 (from top to bottom: 38 μm aluminum, plastic film) has a push-through force 63 of approximately 127 N or approximately 88 N.

Claims

claims

1. A device for testing the push-through force (63) on a blister strip (50), wherein for forming a plurality of cavities (53) for a pharmaceutical drug formulation, a bottom foil (51) and a cover sheet (54) are circumferentially connected to each other, with at least a column (11) with a motor or hydraulically vertically displaceably arranged traverse (12) with a on the blister strip (50) acting punch (15) whose travel via at least one transducer (13) and its force on the blister strip (50) by means of a force transducer (14) are determinable, characterized in that for receiving the blister strip (50) a holder (20) is provided which consists of a base plate (21) and opposite lateral guides (23), between which the blister strip (50) horizontally slidably received, wherein the blister strip (50) with its cover sheet (54) on the base plate (21).

2. Apparatus according to claim 1, characterized in that the punch (15) has a spherical, in particular replaceable punch head (16) acting on the as a cup (52) from the bottom foil (51) Kavitat (53) acts.

3. Apparatus according to claim 1 or 2, characterized in that the base plate (21) in the range of request- tion of the axis of the punch (15) with the punch head (16) has a recess (22).

4. Device according to one of claims 1 to 3, characterized in that the guides (23) are arranged laterally displaceable on the base plate (21) and at different distances from each other or to the center of the recess (22) are fixable.

5. Device according to one of claims 1 to 4, characterized in that the guides (23) cover the Blisterεtreifen (50) at least partially.

6. Device according to one of claims 3 to 5, characterized in that the recess (22) is formed as a bore o- of the blind bore, whose axis lies in the extension of the axis of the punch (15).

7. Apparatus according to claim 6, characterized in that the bore or blind bore in its diameter is variable by means of Wechεeleinεätzen,

8. A method for testing the push-through force (63) on a blister strip (50), in which for forming a plurality of cavities (53) for a pharmaceutically active substance formulation a bottom film (51) and a cover film (54) are circumferentially connected to one another Device having at least one column (11) with a motor or hydraulically displaceable vertically arranged traverse (12) with a on the blister strip (50) acting punch (15) whose travel ü at least one displacement sensor (13) and its force on the blister strip (50) are determined by means of a force transducer (14), characterized in that the blister strip (50) with the cover film (54) down into one of a base plate (21) and opposite lateral guides (23) inserted existing holder (20), and then by means of a punch (15) attached to the punch head (16) formed as a cup (52) cavity (53) of the bottom foil (51) down into a recess ( 22) of the base plate (21) until the tearing of the cover sheet (54) is pressed and the moment of tearing the maximum force is determined as push-through force (63).

9. The method according to claim 8, characterized in that the determination of the push-through force (63) with central force (64) and / or lateral force (65) is performed, wherein the cup (52) formed as the cavity (53) of the bottom foil (51) is completely or partially positioned under the punch head (16).

10. The method according to claim 8 or 9, characterized in that the test at a defined Verfahrge- εchwindigkeit of the traverse (12) with the punch (15) is performed.

11. The method according to claim 8 or 9, characterized in that during the course of the process, the travel as stretching of the blister strip (50) and the force (64, 65) on the blister strip (50). recorded, stored and displayed in a force-strain diagram (60).