DE10056855A1 - Product, e.g. pharmaceutical, consisting of a laminate comprising a moisture- and/or oxygen-sensitive layer and a moisture- and/or oxygen-absorbing layer in air- and moisture-impermeable packaging - Google Patents

Abstract

Product consisting of a laminate comprising a moisture- and/or oxygen-sensitive layer (1) and a moisture- and/or oxygen-absorbing layer (2) in air- and moisture-impermeable packaging is new. An Independent claim is also included for preparing the product, comprising: (a) forming a layer (1) comprising a moisture- and/or oxygen-sensitive polymer or drug; (b) forming a layer (2) comprising a desiccant and/or an oxygen absorber; (c) applying layers (1) and (2) to a carrier sheet to form a laminate; (d) subdividing the laminate into individual segments; (e) sealing the segments between two strips of sealable packaging material; and (f) separating the sealed regions of the product to obtain air- and moisture-impermeable bags or blister packs.

Description

The invention relates to a composite laminate built up in layers, in particular a transdermal therapeutic system (TTS) or a flat pharmaceutical dosage form for oral Administration (so-called wafer), which in at least one layer contains active ingredient sensitive to oxygen and / or moisture and which has a further layer which is used to absorb oxygen and 1 or moisture is capable and a method for producing a such composite laminate.

The transdermal administration of active pharmaceutical ingredients has been around since the first commercial use of a scopolamine-containing transdermal Therapeutic system (Scopoderm TTS) known. Others too Active substances (nitroglycerin, estradiol, buprenorphine, clonidine, isosorbide dinitrate, Fentanyl, nicotine, norethisterone acetate etc.) are now in the form of a offered such TTS. For this, the layered, adhesive patches applied to the skin of a patient. The The active ingredient can then be transferred from the TTS to the skin in a controlled manner Patients are given.

Different types of such TTS are e.g. B. by YW Chien in "Developmental Concepts and Practice in Transdermal Therapeutic Systems", in Transdermal Controlled Systemic Medications, ed. By YW Chien, Marcel Dekker, Inc., New York ( 1982 ), Chapter 2, pp. 25-81 Service. According to this, essential elements of a TTS are the active substance-impermeable backing layer, an active substance-containing reservoir or matrix layer, possibly a semipermeable or microporous membrane that controls the release of the active substance from the reservoir, optionally a pressure-sensitive adhesive layer and an anti-adhesive protective layer (so-called release liner), which is removed from the pressure-sensitive skin contact side of the TTS before using the TTS. In order to avoid repetition, the content of this chapter - in particular the TTS types described therein - is to be regarded as part of the disclosure of the present description by reference. Because of its layered structure, a TTS is therefore a composite laminate, that is to say a device constructed from at least two layers.

Furthermore, sheet-like pharmaceuticals are built up in layers Dosage form known for oral administration, if necessary can also be equipped with mucoadhesive. Such dosage forms z. B. in EP 219 762, US 4,367,203, US 4,568,560, US 4,777,046, EP 426 428, EP 259 749, US 5,948,430, US 6,083,531 and EP 460 588 described. These are film-like dosage forms that also be referred to as "wafers" or "wafers" and consist of at least an active ingredient-containing layer. These layers contain in addition the at least one active ingredient is a binder that the dosage form physical form. These are polymers such as Polyethylene glycol, polyvinyl pyrrolidone, starch, cellulose and Cellulose derivatives, polyvinyl alcohol and gelatin. This pharmaceutical Dosage forms can vary within a short period of time dissolve about 5 seconds and about 5 minutes, e.g. B. in the oral cavity.

A problem with the manufacture and storage of TTS or wafers can occur, is based on the sensitivity of individual components, in particular certain active substances against oxygen and / or Humidity. This is to be understood to mean that, when exposed to small amounts of oxygen and / or water a physical and / or chemical conversion of the active ingredient can take place, which leads to that the active ingredient is no longer in its full activity for the pharmaceutical application is available.  

Examples of substances, in particular active pharmaceutical ingredients, which Exposure to moisture will cause the above transformations are acetylsalicylic acid (ASA) and 17β-estradiol. In case of Acetylsalicylic acid undergoes a chemical reaction (hydrolysis), whereby Salicylic acid and acetic acid are formed. In the case of 17β-estradiol there is a physical conversion (crystal formation), whereby hardly soluble water-containing crystals are formed.

Examples of substances, in particular active pharmaceutical ingredients, which Exposure to oxygen will cause the above transformations can be nicotine and N-0923. In these cases there is a chemical Implementation (oxidation), whereby different oxidation products arise can.

As a result of these transformations, the active pharmaceutical ingredient lies in the or the active ingredient-containing layers of the TTS or wafer in a smaller amount Concentration before. In general, however, is high and substantial constant concentration of dissolved active ingredient in the layer or layers of the TTS or wafers required to last for the entire duration of use this pharmaceutical dosage form is sufficiently large Concentration difference between the skin or mucous membrane touching layer of the appropriate dosage form and the skin or mucous membrane of the patient. This Concentration difference is generally the driving force for that Diffusion of the active ingredient into the skin or mucous membrane and ultimately into the bloodstream.

DE 196 46 048 contains packaging for transdermal therapeutic devices Systems described that a drying device fixed on the inside contain. The drying device is flat and contains a solid desiccant.  

US Pat. No. 5,972,452 describes oxygen-absorbing components, that can be glued to the inside of a package, e.g. B. to the Inside of a sealed pouch.

A disadvantage in the manufacture of such desiccants or Oxygen absorbent packaging is that the label containing a desiccant or an oxygen absorber made by separation from a sheet-like laminate, in one second work step with an intermediate cover and in one third work step with removal of this abhesive finish Intermediate cover exactly on the web, which later the inside of the Packaging results, must be positioned and permanently glued. In The TTS or the wafer must also carry out a separate operation the relevant moisture and / or oxygen sensitive active ingredient getting produced.

Finally, the pharmaceutical dosage form (TTS or wafer) must be like this on the packaging laminate web stuck with the individual labels put on and this sheet is sealed and cut so that the Desiccant label does not lie on the resulting weld seams. The implementation of these various steps and procedures must with the exclusion of oxygen or with greatly reduced air humidity take place, which may also require rapid work. This However, due to the required accuracy in positioning the Desiccant labels on the laminate or the positioning of the TTS the laminate glued in this way is technically very demanding and very technical consuming.

The object of the present invention is therefore to provide a device for To make available through which a composite laminate, in particular a Transdermal therapeutic system (TTS) or one in layers  constructed, flat pharmaceutical dosage form for oral Administration (wafer), which in at least one layer contains active ingredient sensitive to moisture and / or oxygen, in a closed gas room under reduced humidity (practically with exclusion of moisture) and under reduced Oxygen content (practically excluding oxygen) can be stored can, as well as a method for producing such a device.

In this case, devices with a simpler structure and method that difficulties presented in the manufacture of the prior art avoid known methods to be made available.

This object is achieved according to the present invention by a composite laminate composed of at least two different layers and an airtight and moisture-proof packaging containing this composite laminate. The composite laminate according to the invention contains at least one moisture and / or oxygen sensitive layer ( 1 ) which contains a component sensitive to moisture and / or oxygen (polymeric base material or active substance). The composite laminate according to the invention also contains an active ingredient-free, moisture and / or oxygen absorbing layer ( 2 ) which is capable of absorbing moisture and / or oxygen.

These two separate layers ( 1 ) and ( 2 ) can be adjacent and have direct contact with one another, but embodiments are preferred in which these two layers are spatially separated from one another. The composite laminate can preferably be a transdermal therapeutic system or a wafer with at least one active ingredient which is sensitive to moisture and / or oxygen.

The moisture sensitivity of layer ( 1 ) can also be based on the fact that it contains a moisture-sensitive component. On the one hand, this includes a moisture-sensitive material from which the layer is built and which therefore essentially has a carrier function. Such materials generally consist of one or more polymeric base materials. This includes materials that are made up of those molecules in which one or more types of atoms or groupings of atoms are repeatedly strung together. Moisture-sensitive polymeric base materials can e.g. B. polyvinyl acetate, polyvinyl alcohol, polyvinyl pyrrolidone, polyanhydrides, biopolymers, cellulose, gelatin, cellulose products, water-swellable polymers and other macromolecular substances that dissolve, swell or chemically convert when exposed to moisture (essentially water).

In general, the component that is sensitive to moisture this layer, but at least one in this layer contained moisture-sensitive, pharmaceutical active ingredient. For this include acetylsalicylic acid, diamorphine, 17β-estradiol, fentanyl, lobeline, Morphine, nicotine, norethisterone acetate, oxybutinin, selegiline, sildenafil, Testosterone and hydrolysis sensitive esters.

In addition to moisture-sensitive substances, substances can also be used count a relatively high molecular weight, such as. B. insulin and others known protein substances.

The oxygen sensitivity of layer ( 1 ) is caused by an oxygen-sensitive pharmaceutical active ingredient contained in this layer. These include, among others, nicotine, N-0923 = (-) - 5,6,7,8, -Tetrahydro-6- [propyl [2- ( 2- thienyl) - ethyl] amino] -1-naphthol, oxygen-sensitive biopolymers, proteins , substances susceptible to oxidation such as amines, alcohols, aldehydes and also substances with isolated and / or conjugated C = C double bonds.

The composite laminate according to the invention further contains an active ingredient-free, moisture and / or oxygen absorbing layer ( 2 ). Such a layer capable of absorbing moisture and / or oxygen can consist of at least one polymeric material which serves as a carrier material for a drying agent and / or an oxygen absorber. Such polymeric materials include polyethylene, polypropylene, polyacrylate, polyisobutene, polystyrene, polyvinyl chloride, polyvinylidene chloride, synthetic rubber, silicones, ethylene vinyl acetate, and other thermoplastics and elastomers known to those skilled in the art.

Suitable desiccants include solids in particular. These include mineral substances such as silica gel, molecular sieve, calcium sulfate (CaSO ₄ , anhydrite), aluminum oxide Al ₂ O ₃ , calcium oxide CaO, potassium carbonate K ₂ CO ₃ , sodium carbonate Na ₂ CO ₃ , sodium sulfate Na ₂ SO ₄ , and other suitable drying agents and solids known to those skilled in the art, and mixtures thereof.

Suitable oxygen absorbers include: Irganox, Irgafox, Butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, pyrogallol, etc.

The desiccant and / or the oxygen absorber are in the moisture and / or oxygen absorbing layer ( 2 ) in an active state in which the desiccant and / or the oxygen absorber contained therein for absorbing moisture (water molecules) and / or oxygen (O ₂ molecules) is / are capable. The desiccant may have to be converted from this inactive state, in which it is not capable of absorbing moisture, to this active state.

The content of desiccant and / or oxygen absorber in the layer ( 2 ) depends essentially on the requirements of the manufacturing process and the moisture and / or oxygen sensitivity of the layer ( 1 ), which are caused by the components contained therein (polymeric materials, active pharmaceutical ingredients) is determined. If working in the absence of air and oxygen is economically justifiable, the desiccant and / or oxygen absorber content can be set low. If working in the absence of air and oxygen is not economically justifiable and / or the moisture and / or oxygen sensitivity of layer ( 1 ) is not extremely pronounced, the desiccant and / or oxygen absorber content should be set higher. In general, the content of desiccant and / or oxygen absorber in layer ( 2 ) can be between 0.5 and 30% by weight, preferably between 2 and 25% by weight, particularly preferably between 5 and 20% by weight.

The desiccant and the oxygen absorber are not or only in very small amount of diffusion from the moisture and / or oxygen absorbing layer, d. H. these substances are in practically immobilized this layer.

In certain embodiments, the moisture and / or oxygen-absorbing layer ( 2 ) can be provided with a pressure-sensitive adhesive, but in certain embodiments it can also be non-pressure-sensitive or at least only pressure-sensitive on one side. In order to provide the layer ( 2 ) with pressure-sensitive adhesive, it may be necessary to use pressure-sensitive polymers or non-pressure-sensitive polymers with the addition of tackifiers as the polymeric material. Pressure-sensitive polymers and / or non-pressure-sensitive polymers with suitable tackifiers are known to the person skilled in the art. Adhesive polymers include e.g. B. polyacrylates, polyisobutene, silicones; Tackifiers are e.g. B. Resins such as rosin.

In order to provide the layer ( 2 ) with pressure-sensitive adhesive only on one side, a non-adhesive layer must be laminated onto one side of the layer ( 2 ) which is provided with pressure-sensitive adhesive.

The moisture content of the layer ( 1 ) sensitive to oxygen and / or moisture can be kept constant by the simultaneous presence of the moisture and / or oxygen-absorbing layer ( 2 ) in the composite laminate and / or between two specific, desired limit values. In a preferred embodiment, the moisture content of the layer ( 1 ) of the composite laminate is below 2% by weight, preferably between 1 and 0.02% by weight.

The oxygen content of the layer ( 1 ) sensitive to oxygen and / or moisture can be kept constant and / or between two specific, desired limit values by the simultaneous presence of the oxygen-absorbing layer ( 2 ) in the device. In a preferred embodiment, the oxygen content of layer ( 1 ) of the composite laminate is below 0.2% by weight, preferably between 0.1 and 0.002% by weight.

Also, the moisture content and / or the oxygen content of the air surrounding the composite laminate in the airtight and moisture-tightly sealed packaging can be reduced by the presence of the moisture and / or oxygen-absorbing layer ( 2 ) in the composite laminate and / or between two specific ones , desired limit values can be set constantly. In a preferred embodiment, the moisture content of the air present in the packaging is below 2% by weight, preferably between 1 and 0.02% by weight. In a preferred embodiment, the oxygen content of the air present in the packaging is below 1% by weight, preferably between 0.1 and 0.02% by weight.

In the event that the desiccant and / or oxygen absorber does not practically occur in the layer ( 1 ) and / or at least has no adverse effects on the layer ( 1 ), the use of an additional separating layer can be dispensed with. In such an embodiment, the layer ( 1 ) sensitive to moisture and oxygen and the layer ( 2 ) absorbing moisture and / or oxygen can be present in two separate layers adjacent to one another, in particular one on top of the other, and have direct contact with one another.

The spatial separation of the two different layers ( 1 ) and ( 2 ) within the composite laminate is, however, a further characteristic of this composite laminate in certain embodiments. This spatial separation of the two different layers can be realized in different ways. In one case there is a horizontal separating layer ( 3 ) between the two layers, in the other case there is a vertical separating layer ( 4 ). It has the function of preventing the desiccant and / or oxygen absorber from entering the layer ( 1 ) and / or the active pharmaceutical ingredient from entering the layer ( 2 ).

A specific embodiment for a horizontal separating layer ( 3 ) is a protective layer which is arranged below the layer ( 1 ) and above the layer ( 2 ). This case represents a very simple and therefore preferred embodiment. It is shown in FIG. 1.

Fig. 1 shows a composite laminate with a horizontal separating layer (3), a single-sided pressure-sensitive adhesive layer (2) and an open at the sides of layer (1). The horizontal separating layer ( 3 ) also serves as a common carrier layer of layer ( 1 ) and layer ( 2 ) and as a protective layer (release liner) for layer ( 1 ). It is therefore identical to the protective layer of a conventional TTS. Layer ( 1 ) is covered at the top by the back layer ( 5 ), which can be permeable or impermeable to moisture and / or oxygen.

The moisture and / or oxygen absorbing layer ( 2 ) is preferably congruent (with the same area) as the horizontal separating layer ( 3 ), but it can also be smaller than the area of the horizontal separating layer ( 3 ). In this embodiment, layer ( 2 ) is provided with a pressure-sensitive adhesive on one side, so that it is firmly connected to the horizontal separating layer ( 3 ) and is only removed together with this layer, which also serves as a protective layer, immediately before application of the remaining layers of the composite laminate. The horizontal separating layer ( 3 ) can be impermeable to moisture; however, an embodiment which is permeable to moisture but at the same time impermeable to the moisture-sensitive component is preferred. When using a moisture-impermeable horizontal separating layer ( 3 ), a moisture-permeable backing layer ( 5 ) is preferably used.

In the event that the backing layer ( 5 ) is impermeable to moisture and / or oxygen and that at the same time it completely closes off the layer ( 1 ), that is to say laterally from the surroundings, such a moisture-permeable horizontal separating layer ( 3 ) is used, which at the same time represents the protective layer ( 6 ). Such a composite laminate is shown in FIG. 2.

In a further embodiment, the horizontal separating layer ( 3 ) consists of an intermediate layer which is arranged above the layer ( 1 ) and below the layer ( 2 ). In contrast to the embodiments shown in Fig. 1 and Fig. 2 embodiments, in this embodiment, separation of the layer (2) must be not necessarily immediately prior to application of the composite laminate. This depends on the special structure of the composite laminate:
If the horizontal separating layer ( 3 ) on the side facing the layer ( 2 ) is equipped with an adhesive or if the side of the layer ( 2 ) facing the horizontal separating layer ( 3 ) is equipped with an adhesive, a separation of the layer ( 2 ) including the backing layer can be performed ( 5 ). This case is shown schematically in FIG. 3. In this case, the layer ( 2 ) can optionally also be identical to the back layer ( 5 ) of the composite laminate.

However, if neither the horizontal separating layer ( 3 ) nor the layer ( 2 ) are equipped with at least one side with an adhesive and / or if the bond between these two layers is covered by a common backing layer ( 5 ) which completely closes the bond between these layers and the environment, the layer ( 2 ) cannot be separated. This is shown in FIG. 4. The composite laminate shown has a horizontal separating layer ( 3 ) which represents an intermediate layer within the device which is permeable to moisture and / or oxygen. The backing layer ( 5 ) and protective layer ( 6 ) completely close the composite of layer ( 2 ), horizontal separating layer ( 3 ) and layer ( 1 ) from the surroundings.

In such an embodiment, in which the layer ( 2 ) is applied together with the remaining layers of the device, it can happen that the desiccant and / or the oxygen absorber contained therein during the period of use by water and / or oxygen absorption in the inactive state is reset.

In Fig. 5 it is shown that the moisture-absorbing layer ( 2 ) can also be applied above the conventional backing layer. In this case the horizontal separating layer ( 3 ) is identical to such a backing layer. If the side of the horizontal separating layer ( 3 ) facing the layer ( 2 ) or the side of the layer ( 2 ) facing the horizontal separating layer ( 3 ) is equipped with adhesive, this layer ( 2 ) can be separated from the separating layer ( 3 ) before The composite laminate is applied.

The case of a vertical separating layer ( 4 ) is preferably used when a particularly flat device is to be produced or when no suitable materials are available for a horizontal separating layer.

The simplest embodiment of the composite laminate according to the invention, which contains a vertical separating layer ( 4 ), is shown in FIG. 6. In this embodiment, the vertical separating layer ( 4 ) consists of a material recess (gap; air-filled, otherwise empty space) between layer ( 1 ) and layer ( 2 ). The back layers ( 5 ) can be the same or different.

However, the vertical separating layer ( 4 ) can also consist of a solid material which is permeable to moisture and / or oxygen and at the same time is essentially impermeable to the moisture-sensitive components of the moisture-sensitive layer ( 1 ). Fig. 7 shows such a composite laminate with a vertical separating layer ( 4 ) made of such a material. The back layer ( 5 ) completely closes layer ( 1 ) and layer ( 2 ) from the surroundings.

In the embodiments with a vertical separating layer ( 4 ), layer ( 1 ) and layer ( 2 ) adhere to the same side of a single protective layer ( 6 ). Layer ( 1 ), layer ( 2 ) and the vertical separating layer ( 4 ) can have different back layers ( 5 ) or the same back layer ( 5 ).

In the embodiments with a vertical separating layer ( 4 ), the geometric shape of layer ( 2 ) and / or layer ( 1 ) is basically irrelevant. A rectangular or square shape is preferred.

It is possible that the moisture and / or oxygen absorbing layer ( 2 ) is separated from the other layers of the composite laminate together with the protective layer ( 6 ) before the pharmaceutical dosage form is applied. This is e.g. B. possible in the embodiment of FIG. 6. If an embodiment as in Fig. 7 is used, this is not possible.

In FIG. 8 is a further composite laminate is shown, is disposed around a central circular layer (1) annularly in the layer (2) which is separated by an annular vertical separating layer (4). It is clear that layer ( 1 ) can in principle also be arranged in a ring around a circular layer ( 2 ) in such a manner.

FIG. 9 shows a composite laminate in which layer ( 1 ) and layer ( 2 ) are adjacent to one another in two separate layers and have direct contact with one another. An additional separating layer in between was dispensed with due to the absence of the interactions described above, which are essentially caused by the diffusion of contents of one layer into the other layer.

FIG. 10 shows an embodiment as in FIG. 9, but the combination of layer ( 1 ) and layer ( 2 ) is additionally covered by a back layer ( 5 ). As a result, the two layers are completely sealed off from the environment.

The usual further components of a TTS (backing layer, microporous and / or semi-permeable membrane, additional pressure-sensitive adhesive layer, fleece, etc.) can optionally be arranged around the layer ( 1 ) in all the embodiments discussed and illustrated or can be contained in the layer itself.

The usual other components of a wafer are in the generally only around a carrier layer, e.g. B. siliconized paper or an abhesive plastic film.  

The sealable packaging materials used for the production of air and moisture-proof sealed bags and / or blister packs Barex, Surlyn, ethylene vinyl acetate, with sealing medium coated plastic and / or metal foils and others, the Materials known to those skilled in the art.

The process according to the invention consists in that the layer ( 1 ) sensitive to moisture and / or oxygen and the layer ( 2 ) absorbing moisture and / or oxygen are produced in two separate steps - in a conventional manner.

The layers ( 1 ) and ( 2 ) produced in this way are then applied to the same carrier layer, possibly in time and / or in succession or simultaneously and / or side by side. The two layers can also be applied directly opposite one another on the top and bottom of the same carrier layer.

In the embodiments, a horizontal layer can be used as the carrier layer Interface the horizontal interface itself and in the Embodiments with a vertical separation layer a common Carrier layer, e.g. B. serves as a protective layer release liner.

The production of the layer ( 1 ) sensitive to moisture and / or oxygen is fundamentally known to the person skilled in the art and can be carried out in a conventional manner, eg. For example: mixing the components such as polymeric material, active ingredient, if necessary tackifier, plasticizer, solvent, binder, crosslinker etc. and spreading out the mixture and stripping off the solvent, extrusion in the case of solvent-free mixtures, spraying an active ingredient-free polymeric base material with active ingredient in liquid or dissolved Form, etc. Of course, the components of this mixture also contain the components sensitive to moisture and / or oxygen.

The production of a moisture and / or oxygen absorbing layer ( 2 ) is also known in principle. It can be carried out in the same conventional manner as the production of layer ( 1 ). However, at least one desiccant and / or at least one oxygen absorber are used.

To absorb pressure-sensitive moisture and / or oxygen To obtain the layer, the polymeric base material may have to be used be pressure-sensitive adhesive or a tackifier is added to the mixture become. This mixture is then placed on an intermediate cover streaked. Only one-sided around this pressure-sensitive adhesive layer to provide pressure-sensitive adhesive, an additional non-adhesive is used End cover.

Another process step can be the activation of the desiccant. This is to be understood to mean that the desiccant contained in layer ( 2 ) is converted from an inactive state which does not enable it to absorb moisture to an active state which enables it to absorb moisture. This can be done in several ways, e.g. B. by heating to elevated temperatures and / or storage under extremely dry conditions and / or greatly reduced external pressure. Other methods and conditions for activating the desiccant are known to the person skilled in the art.

The drying agent in layer ( 2 ) can be activated before the laminate is made up of layer ( 2 ), carrier layer and layer ( 1 ). However, it can also take place after the production of this laminate, provided that the conditions of the activation have no adverse effects on layer ( 1 ) or other components of the composite laminate. It is clear that after the desiccant has been activated or when a moisture-absorbing polymeric material is used, the other subsequent or all process steps should be carried out with exclusion or with greatly reduced air humidity and / or particularly quickly.

Activation of the oxygen absorber is not provided since it is processed in the active state. However, this means that after the production of the oxygen-absorbing layer ( 2 ), the subsequent process steps should be carried out in the absence of atmospheric oxygen and / or particularly quickly.

Further process steps in the production of a composite laminate according to the invention can be the following: For example: a backing layer ( 5 ), an additional nonwoven layer, a semi-permeable or a microporous membrane, an additional pressure-sensitive adhesive layer, further protective layers on layer ( 1 ) and / or layer ( 2 ).

With regard to the central process steps, the point in time at which these further process steps are carried out depends on the structure which the composite laminate according to the invention should ultimately have. The person skilled in the art knows whether a corresponding method step has to be carried out before, simultaneously or after the central work steps. So z. B. the application of a common additional backing layer ( 5 ) after production of the composite laminate from layer ( 1 ) and layer ( 2 ) may be advantageous, while the application of a membrane on layer ( 1 ) before production of the composite containing layer ( 1 ) and layer ( 2 ) may be more appropriate.

The final process steps are the separation of the composite laminate by cutting or punching and laying on the isolated pattern  (Die-cuts) of the composite laminate (especially single TTS and individual wafers) on sheet-like packaging materials, which then with other sheet-shaped packaging materials covered, sealed and get cut. You get airtight and moistureproof Packaging (especially sealed edge bags or thermoformed blisters), the contain at least one composite laminate according to the invention.

The underlying object is achieved in a surprising and particularly simple manner by the present invention. One advantage is that the moisture and / or oxygen absorbing layer is now contained directly in the composite laminate which also contains the layer sensitive to moisture and / or oxygen. The illustrated embodiments also avoid possible incompatibility problems between the ingredients of layers ( 1 ) and ( 2 ). The airtight and moistureproof packaging ensures a long shelf life of the composite laminate.

The method according to the invention is due to the elimination of separate Manufacturing processes for a desiccant and / or Simplified label containing oxygen absorber.

The following example illustrates the manufacture of a composite laminate explain.

example 1

On a first supply roll ( 7 ) there is a conventionally produced layer ( 9 ) containing 5% by weight CaSO ₄ (anhydrous) and 10% by weight ascorbic acid, which is covered with a protective film ( 10 ) with an adhesive coating , A second supply roll ( 8 ) contains a layer ( 11 ) containing N-0923 as an oxygen-sensitive active ingredient and polyvinyl alcohol as a fastness-sensitive component. This layer ( 11 ) is also pressure-sensitive adhesive and is equipped with a backing layer ( 12 ) and an abhesive intermediate cover ( 13 ).

The laminate on the first supply roll ( 7 ) is unrolled. The intermediate cover ( 13 ) is pulled off the laminate located on the second supply roll ( 8 ) and the side of the layer ( 11 ) which has been provided with a pressure-sensitive adhesive is applied to the back of the protective film ( 10 ) of the laminate rolled off from the first supply roll ( 8 ).

The contours of individual pharmaceutical dosage forms are punched out of the laminate of backing layer ( 12 ) and layer ( 11 ) on a subsequent lifting punch ( 14 ). The protruding edge is trimmed off. On a further punching device, knobs and / or removal aids in the form of cuts are punched onto the protective film ( 10 ).

Finally, the protective film on another punching device ( 15 ), for. B. a punch. The composite laminates separated by such cross cutting are placed on a sheet of a sealable material and sealed in a conventional manner.

Due to the fact that the supply roll ( 7 ) was stored in an oxygen-free and essentially water-free protective gas atmosphere before it was processed in this process, additional gassing of the entire device with an oxygen-free protective gas atmosphere could be dispensed with in the process.

The procedure described in this example is shown schematically in FIG. 11.

Claims (16)

1. A device comprising an airtight and moisture-proof packaging and a composite laminate consisting of at least two layers, characterized in that a first layer of the composite laminate is a layer ( 1 ) sensitive to moisture and / or oxygen and a second layer of the Composite laminate is a moisture and / or oxygen absorbing layer ( 2 ). 2. Device according to claim 1, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate contains a moisture-sensitive polymeric material. 3. Apparatus according to claim 1 or 2, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate contains a moisture-sensitive pharmaceutical active ingredient. 4. Device according to one of claims 1 to 3, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate contains an oxygen-sensitive polymeric material. 5. Device according to one of claims 1 to 4, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate contains an oxygen-sensitive pharmaceutical active ingredient. 6. Device according to one of claims 1 to 5, characterized in that the moisture and / or oxygen-absorbing layer ( 2 ) of the composite laminate contains at least one drying agent and / or at least one oxygen absorber. 7. Device according to one of claims 1 to 6, characterized in that the composite laminate contains a horizontal separating layer ( 3 ) or a vertical separating layer ( 4 ), the spatial separation of the moisture and / or oxygen sensitive layer ( 1 ) from the Moisture and / or oxygen absorbing layer ( 2 ) causes. 8. Device according to one of claims 1 to 7, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate is a moisture-sensitive polymeric material from the group polyvinyl acetate, polyvinyl alcohol, polyvinylpyrrolidone, polyanhydride, cellulose, cellulose derivatives or a copolymer is, which contains at least one of the monomers as a basic building block, from which polyvinyl acetate, polyvinyl alcohol, polyvinyl pyrrolidone, polyanhydride, cellulose, cellulose derivatives are constructed. 9. Device according to one of claims 1 to 8, characterized in that the moisture and / or oxygen sensitive layer ( 1 ) of the composite laminate is pressure-sensitive adhesive or mucoadhesive. 10. Device according to one of claims 1 to 9, characterized in that the moisture and / or oxygen-absorbing layer ( 2 ) of the composite laminate is pressure-sensitive adhesive or mucoadhesive. 11. Device according to one of claims 1 to 10, characterized in that the moisture and / or oxygen-absorbing layer ( 2 ) of the composite laminate is a drying agent from the group silica gel, molecular sieve, Na ₂ SO ₄ , Na ₂ CO ₃ , CaSO ₄ , Al ₂ O ₃ , CaO, K ₂ CO ₃ or a combination thereof. 12. Device according to one of claims 1 to 11, characterized in that the moisture and / or oxygen absorbing layer ( 2 ) of the composite laminate contains an oxygen absorber from the group Irganox, Irgafox, ascorbic acid, butylated hydroxyanisole, butylated hydroxytoluene, pyrogallol or a combination thereof. 13. The device according to one of claims 1 to 12, characterized characterized that the air and moisture proof packaging Sealed edge bag or a blister pack. 14. A method for producing a device comprising an air- and moisture-tight packaging and a composite laminate contained therein, consisting of at least two layers, characterized in that

• a) a first layer ( 1 ) sensitive to moisture and / or oxygen is produced, at least one polymeric material sensitive to moisture and / or oxygen or one pharmaceutical active substance sensitive to moisture and / or oxygen being used,
• b) a moisture and / or oxygen-absorbing layer ( 2 ) is produced, at least one desiccant and / or one oxygen absorber being used,
• c) the layer ( 1 ) sensitive to moisture and / or oxygen and the layer ( 2 ) absorbing moisture and / or oxygen are applied to a carrier layer,
• d) the composite laminate, which contains the moisture and / or oxygen sensitive layer ( 1 ), the moisture and / or oxygen absorbing layer ( 2 ) and the carrier layer, is divided into individual sections,
• e) the individual sections of the composite laminate are transferred to a sealable packaging material web, covered with a further sealable packaging material web and sealed,
• f) the sealed areas of the stacked packaging material webs are severed, resulting in individual air and moisture-tight sealing bags or blister packs.

15. A method for producing a device according to claim 14, characterized in that layer ( 1 ) and layer ( 2 ) of the composite laminate are applied on opposite sides or on the same side of the carrier layer. 16. A method for producing a device according to one of the Claims 14 to 15, characterized in that at least one of the steps a, b), c), and d) to the exclusion of Humidity and / or atmospheric oxygen takes place.