Lamination method and product

Abstract

The present invention provides a method for manufacturing a mechanically strong laminated film that offers impermeability and inertness to packaging, while remaining unseparable, undeformable, unperforated, sealable, and otherwise resistant to mechanical impact. [Solution] A method for manufacturing a laminated film relating to a new laminated film, wherein the contact layer is bonded and laminated to a base layer such as a metal foil, or a co-extruded layer including the contact layer and at least one tie layer is bonded to a base layer, and the laminated film is used to wrap APIs such as nicotine, fentanyl, lidocaine and rivastigmine, and the contact layer comprises COC, PA, EVOH, CBC, PVDF, COP, HDPE or EMAA.

Description

[Technical Field]

[0001] The present invention relates to a novel laminated film in which a contact layer is bonded and laminated to a base layer such as a metal foil, or thereby a co-extruded layer including a contact layer and at least one tie layer is bonded to a base layer, and to the use of the laminated film for wrapping APIs (active pharmaceutical ingredients) such as nicotine, fentanyl, lidocaine, and rivastigmine. [Background technology]

[0002] In the pharmaceutical industry, highly active substances such as nicotine, fentanyl, rivastigmine, and lidocaine are filled as tablets in inhalers, patches, etc., resulting in special requirements for packaging, lamination, or film used to seal these substances to ensure that harmful decomposition or ingestion does not occur.

[0003] The requirements for packaging, film, or lamination are typically as follows: - Mechanically stable laminates that do not separate or deform - To enhance the safety of potentially hazardous compounds, ensure that packaging is safe for children. - Inert properties ensure that the compound does not move from the external environment of the layer through the layer and come into contact with the sealed material. - The enclosed API does not react with, or move through or into, the surface it is in contact with.

[0004] A commercially used polymer that meets some or all of the requirements for extreme chemical resistance and inertness is polyacrylonitrile (PAN) films, which are sold as resins under the trademark Barex®, manufactured, among other things, by Ineos. Barex® is widely used and approved for pharmaceutical and food applications because it provides a good barrier to oxygen, nitrogen, and carbon dioxide compared to other common polymers, and because it has excellent chemical resistance to various functional groups such as hydrocarbons, ketones, esters, alcohols, bases, and acids, as well as / or drugs such as nicotine.

[0005] Furthermore, the extruded Barex® resin is thermally stable and therefore can be welded at temperatures of approximately 160 to 220°C, making it suitable for use in flexible packaging. However, Barex® is difficult to manufacture and subsequently extrude into film, resulting in high material loss and thus being sold at a high price. In addition, the water and oxygen resistance of Barex® is not satisfactory for all purposes.

[0006] Furthermore, a solution is described in the applicant's WO2017 / 114922, which discloses a laminated film having a co-extruded or co-extruded coating comprising a tie layer and a contact layer, wherein the contact layer is the innermost layer facing a highly active chemical agent such as rivastigmine, nicotine, fentanyl, or lidocaine. The contact layer may contain a polyamide, a cyclic olefin copolymer, or ethylene vinyl alcohol. The tie layer is co-extruded onto the base layer such that the tie layer is in contact with the base layer and the contact layer.

[0007] Further solutions are described in WO2015 / 123211, which discloses a film having a tie layer and a contact layer containing a COC and PE blend that faces a drug such as nicotine. The film can be manufactured by providing a co-extruded layer or by adhesive lamination.

[0008] However, given the expanding market and the demand for flexible packaging, there is an urgent need to find various solutions and methods for manufacturing strong, durable laminates in a cost-effective manner that have the same or improved properties compared to prior art products. [Overview of the project]

[0009] Given this background, an object of the present invention is to provide a solution that satisfies one or more of the above-mentioned needs, namely, a solution that provides impermeability and inertness to packaging, while providing a mechanically strong laminate that does not separate, deform, or perforate, is sealable, and is otherwise resistant to mechanical impact, and further provides an alternative method for manufacturing such products having similar or improved properties.

[0010] One solution involves adhesive lamination. Adhesive lamination allows for high-speed manufacturing, the ability to be used in a wide variety of films, and the creation of thin films. Therefore, adhesive lamination is not as specialized as, for example, extrusion coating, which incurs higher capital costs. In addition, adhesive lamination offers higher lamination strength and provides a good alternative to extrusion coating when providing new laminated films in other ways.

[0011] Therefore, in a first embodiment, this is solved by providing a method for providing a laminated film, the method comprising the following steps: i) A step of providing a base layer that is water-resistant and / or oxygen-resistant. ii) Step of providing a contact layer ii) A step of laminating the base layer onto the contact layer, preferably by adhesive lamination or extrusion lamination. The contact layer comprises a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

[0012] Preferably, the contact layer consists of one substance which is a polymer selected from the group consisting of cyclic olefin copolymer, polyamide, ethylene vinyl alcohol, cyclic block copolymer, polyvinylidene fluoride, cyclic olefin polymer, high density polyethylene, or ethylene-methacrylic acid copolymer and physical variations thereof.

[0013] The contact layer may be one or more layers. Preferably, the contact layer is a single layer. In certain embodiments, the contact layer is a single layer consisting of one substance.

[0014] The adhesive lamination can be carried out either by solventless lamination or solvent-based lamination, and preferably the lamination is solvent-based. Preferably, the solvent is ethyl acetate or methyl ethyl ketone, although other suitable solvents are contemplated and are within that range. The adhesive is preferably a two-component adhesive based on polyurethane and aromatic or aliphatic amines. Such two-component adhesives are well known in the art. Solvent-based adhesive lamination is preferred because it allows for longer chains, which results in a stronger bond of the lamination.

[0015] Preferably, the base layer and the contact layer are directly adhesively laminated, which means that there is no additional layer between the adhesive layers.

[0016] As an alternative to the subsequent lamination, extrusion lamination can be used. The extrusion lamination may use a copolymer made from a material selected from copolymers of ethylene and acrylic acid, copolymers of ethylene and methacrylic acid, and terpolymers containing ethylene, an acrylic ester, and a third polymer. The third polymer is preferably glycidyl methacrylate, more preferably maleic anhydride. Alternatively, the extrusion lamination may use PMMA.

[0017] Extrusion lamination with PMMA may be particularly beneficial when the contact layer contains PVDF or is PVDF. An example of a suitable PMMA is Plexiglas® HFI7. Preferably, the PMMA is pure.

[0018] Preferably, the base layer is laminated to at least a first outer layer, and preferably the first outer layer includes polyethylene terephthalate (PET), polyethylene (PE), paper, or a combination thereof.

[0019] Typically, the thickness of each of the contact layer or the single layer of the contact layer ranges from 20 to 60 μm, but it can also be considered from 15 to 20 μm.

[0020] In one embodiment, the contact layer is polyamide, and the side of the polyamide layer facing away from the base layer contains amorphous polyamide. Preferably, the amorphous polyamide layer and one or more crystalline polyamide layers are co-extruded. In this embodiment, the contact layer is not a single layer.

[0021] In the embodiment where the contact layer is PA, the contact layer is not corona-treated on the amorphous PA side facing away from the base layer. Preferably, the side of the contact layer facing the base layer is corona-treated before lamination.

[0022] By applying amorphous PA and / or by not corona-treating the side of the contact layer facing away from the base layer, i.e., the sealing side of the contact layer, the polyamide layer becomes weldable / sealable at lower temperatures starting at around 140 to 160°C, in contrast to commercially used PA (e.g., PA6 or PA66 available from BASF) which require much higher temperatures up to 230°C.

[0023] Good sealing / welding is achieved when the amorphous PA layer constitutes approximately 10 to 40% of the contact layer thickness, as this is a balance between being able to seal at lower temperatures and obtaining a contact layer that still facilitates smooth manufacturing.

[0024] In other embodiments, the contact layer is a monolayer containing or consisting of COC. When the monolayer is a blend, the COC content of the blend is at least 40% (w / w) of the monolayer.

[0025] In some embodiments where the contact layer is a COC layer, the side of the layer facing the substrate is corona-treated. Typically, when the contact layer is or contains COC, each of the layers constituting the COC layer or the contact layer has a thickness of 18 to 22 μm, preferably 20 μm.

[0026] In a further embodiment, the contact layer comprises or consists of COC co-extruded with the tie layer.

[0027] The tie layer is appropriately made of low-density polyethylene (LDPE), especially when the contact layer is COC.

[0028] In further embodiments, the contact layer is ethylene vinyl alcohol (EVOH). When the contact layer is EVOH, each of the layers constituting the contact layer typically has a thickness of 20 to 50 μm, more preferably 25 to 35 μm, and most preferably 30 μm.

[0029] In further embodiments, the contact layer comprises or is a cyclic block copolymer, and the layer has a thickness of 20 to 60 μm.

[0030] In further embodiments, the contact layer comprises or is polyvinylidene fluoride, and the layer has a thickness of 15 to 50 μm.

[0031] In further embodiments, the contact layer comprises or is a cyclic olefin polymer, and the layer has a thickness of 20 to 60 μm.

[0032] In further embodiments, the contact layer comprises or is high-density polyethylene, and the layer has a thickness of 15 to 60 μm.

[0033] In further embodiments, the contact layer comprises or is an ethylene-methacrylic acid copolymer, and the layer has a thickness of 15 to 50 μm.

[0034] In further embodiments, the contact layer comprises or is a polyamide, and the layer has a thickness of 15 to 60 μm.

[0035] In further embodiments, the contact layer is a cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylate copolymer (EMAA).

[0036] All embodiments and variations of embodiments are intended to be usable to seal in highly active ingredients, preferably lidocaine, amphetamine, testosterone, fentanyl, oxymorphone, tetrahydrocannabinol, rivastigmine, nicotine, diclofenac, dexidibprofen, ibuprofen, Dl-camphor, dextromethorphan, ondansetron, donepezil, methylphenidate, isopropyl myristate, i-methol, methyl salicylate, diphenhydramine, tolbuterol, buprenorphine, clonidine, scopolamine, etc., with fentanyl, nicotine, lidocaine, or rivastigmine being preferred.

[0037] Therefore, in further variations, the laminated film or final laminated film encapsulates the composition, and the laminated film is sealed / welded into pouches, sachets, or used as a lid film for containers.

[0038] Laminated films are also provided, each comprising at least one base layer that is water-resistant and / or oxygen-resistant, and a contact layer bonded to the base layer, wherein the contact layer comprises or consists of a polymer selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), high-density polyethylene (HDPE), or ethylene-methacrylate copolymers (EMAA). The contact layer may be adhesively bonded to the base layer. It is understood that the method used to bond the contact layer to the base layer may be adhesive lamination or extrusion lamination. Films can be manufactured according to the methods outlined in the first aspect of the present invention.

[0039] Highly active chemical substances can be filled into the laminated film. The highly active chemical substance may be any suitable substance. For example, it can be selected from lidocaine, amphetamine, testosterone, fentanyl, oxymorphone, tetrahydrocannabinol, rivastigmine, nicotine, diclofenac, dexidibprofen, ibuprofen, Dl-camphor, dextromethorphan, ondansetron, donepezil, methylphenidate, isopropyl myristate, i-methol, methyl salicylate, diphenhydramine, tolbuterol, buprenorphine, clonidine, and scopolamine, and is preferably fentanyl, nicotine, lidocaine, or rivastigmine.

[0040] The invention also provides the use of polymers selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), or high-density polyethylene (HDPE) or ethylene-methacrylate copolymers (EMAA) in the contact layer of films for packaging highly reactive chemicals.

[0041] A second solution involves co-extrusion. Thus, a second aspect of the present invention provides a method for providing a laminated film, the method comprising the following steps: i) A step of providing a base layer that is water-resistant and / or oxygen-resistant. ii) Step of providing a contact layer iii) A step of coating the base layer with a co-extruded layer, wherein the co-extruded layer includes the contact layer and the tie layer. iv) A step that enables bonding of the co-extruded layer to the base layer. The contact layer contains a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

[0042] Preferably, the tie layer has the following: a) Each layer must be loaded at least 3g / m³ 2 is, or b) Loading of multiple layers, at least one of the layers, must be at least 3g / m³ 2 The total load of multiple layers is at least 3g / m³ 2 That is the case.

[0043] It has been found that the loading of (individual) tie layers has an effect on the sealing strength, and the results presented in this application clearly show an increase in sealing strength following an increase in the loading of the contact layer portion of the co-extruded material. However, the 3 g / m of the layer 2 In this region, when the tie layer loading becomes too low, there is a sharp decrease in sealing strength, and when two or more tie layers are present, the total loading of multiple tie layers is 3 g / m³. 2 It is also possible to exceed this.

[0044] In some embodiments, the contact layer consists of one substance which is a polymer selected from the group consisting of cyclic olefin copolymers, polyamides, ethylene vinyl alcohol, cyclic block copolymers, polyvinylidene fluoride, cyclic olefin polymers, high-density polyethylene, or ethylene-methacrylic acid copolymers and their physical variations.

[0045] The contact layer comprises, or may comprise, a polymer selected from the group consisting of cyclic block copolymers (CBCs), polyvinylidene fluoride (PVDFs), cyclic olefin polymers (COPs), high-density polyethylene (HDPEs), or ethylene-methacrylic acid copolymers (EMAAs).

[0046] The contact layer must be at least 5 g / m 2 Preferably at least 10 g / m 2 It may have a loading mechanism.

[0047] Ideally, the tie layer is constructed with 1, 2, 3, 4, or 5 layers.

[0048] In some embodiments, all layers of the tie layer are co-extruded with the contact layer. The co-extruded layer may be co-extruded onto the substrate.

[0049] In some embodiments, the tie layer consists of a single layer which is a copolymer made from a material selected from copolymers of ethylene and acrylic acid, copolymers of ethylene and methacrylic acid, and terpolymers comprising ethylene, an acrylic acid ester, and a third polymer, wherein the third polymer is preferably glycidyl methacrylate, more preferably maleic anhydride.

[0050] In some embodiments, the tie layer comprises at least two layers, the first layer comprising the copolymer described above, and at least the second or more layers comprising a material selected from EEA, PE, EMA, EAA, or a combination thereof.

[0051] In some embodiments, the tie layer or at least one of a group of tie layers may contain or consist of PMMA. A suitable example of PMMA is Plexiglas® HFI7. Such tie layers may be particularly beneficial, especially in extruded coatings, when the contact layer contains or consists of PVDF. Preferably, the PMMA is pure.

[0052] In some embodiments, the contact layer is a polyamide, and the side of the polyamide layer facing away from the base layer contains an amorphous polyamide.

[0053] Preferably, the layer, such as the polyamide layer, is amorphous. In an alternative embodiment, a portion of the layer may be amorphous, for example, 10 to 40% (w / w).

[0054] The laminated film may enclose the composition, and may be sealed in a pouch or sachet, or used as a lid film on a container.

[0055] Preferably, the method further includes the step of laminating at least a first outer layer on the base layer side of the laminated film.

[0056] The overall thickness of the laminated film may be in the range of 70 to 140 μm.

[0057] Laminated films are also provided, each comprising at least one base layer that is water-resistant and / or oxygen-resistant, and a co-extruded layer, the co-extruded layer comprising a tie layer and a contact layer, the contact layer comprising or comprising a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylate copolymer (EMAA). The films can be obtained by the method outlined in a second embodiment of the present invention.

[0058] Highly active chemicals can be filled into the laminated film. The highly active chemical may be any suitable substance. For example, it can be selected from lidocaine, amphetamine, testosterone, fentanyl, oxymorphone, tetrahydrocannabinol, rivastigmine, nicotine, diclofenac, dexidibprofen, ibuprofen, Dl-camphor, dextromethorphan, ondansetron, donepezil, methylphenidate, isopropyl myristate, i-methol, methyl salicylate, diphenhydramine, tolbuterol, buprenorphine, clonidine, and scopolamine, preferably fentanyl, nicotine, lidocaine, or rivastigmine.

[0059] The invention also provides the use of polymers selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), or high-density polyethylene (HDPE) or ethylene-methacrylate copolymers (EMAA) in the contact layer of films for packaging highly reactive chemicals.

[0060] The present invention, including embodiments and variations, will be described in more detail below. [Modes for carrying out the invention]

[0061] The terms "film" or "laminated film" in this invention refer to a product that includes a base layer laminated by, for example, adhesive lamination or extrusion lamination, with the contact layer being co-extruded or co-extruded coated. Further outer layers, such as PET and paper, may be added.

[0062] In the context of this invention, "packaging" is intended to mean a final laminated film used to fill a composition or compound, or a container otherwise sealed with the film according to the present invention.

[0063] The term "highly reactive compound or composition" should be understood as a compound / composition that is reactive with metals, acids, bases, or functional groups such as ketones, alcohols, hydrocarbons and / or esters, and / or volatile, but readily moves through barriers.

[0064] As used in the context of this invention, the terms “oxygen-resistant and water-resistant” refer to materials having an oxygen transport rate (OTR) and / or water vapor transport rate (WVTR) of only 1, preferably only 0.1, as will be further detailed below. The term WVTR may also be called water vapor transmission rate (MVTR). WVTR and MVTR are equivalent.

[0065] The term "mechanically abrasion-resistant layer," used to describe the outer layer, should be understood as a material suitable for the manufacture of flexible packaging. The mechanically abrasion-resistant layer can be selected from, but is not limited to, materials such as polyethylene or polyamide sheets, ortho-phthalaldehyde sheets, or polyester sheets or combinations. Furthermore, the mechanically abrasion-resistant material, i.e., the first outer layer, can be provided as a biaxially oriented film to impart higher mechanical strength, such as tear strength, to the packaging. The term "biaxially oriented" should be understood as the polymer film being stretched in both the longitudinal and transverse directions during manufacturing.

[0066] The term "outside" should be understood in its broadest sense. The term "external environment" is used to define the direction opposite to the side facing the composition or compound sealed by the lamination or packaging of the present invention. This means that the term "external environment" does not depend on whether the additional layer is coated, laminated, or otherwise attached to the film. Therefore, the term is used to specify the direction in which the side of the layer faces.

[0067] According to all embodiments of the present invention, the base layer may be selected from polymers such as commercially available Al foils from Hydro, or AlOx-coated PET films obtained from, for example, Toray Films Europe, or SiOx-coated PET films obtained from Celplast under the trade name Ceramis®, preferably metal foils, such as aluminum foils, polyamides, polyvinylidene chlorides, polyesters coated with silicon or aluminum oxide, and / or fluoropolymers, but are not limited thereto.

[0068] According to the present invention, the water resistance and / or oxygen resistance preferably have an oxygen transmission rate (OTR) of 1 cm 3 / m 2 / 24 hr / bar or less at 23 °C and 0% RH in accordance with ASTM standard D3985, and / or a water (or moisture) vapor transmission rate (WVTR) of 1 g / m 2 / 24 hr or less at 38 °C and 90% RH in accordance with ASTM standard F1249, preferably both WVTR and OTR are each 0.01 g / m 2 / 24 hr or 0.01 cm 3 / m 2 / 24 hr / bar or less.

[0069] According to the present invention, the base layer of the film is selected to provide a number of properties to the laminated film and the packaging containing the laminated film. The base layer can impart the desired barrier and support properties to the final laminate / package. Further, the base layer may be a gas and water impermeable layer, more preferably a water resistant and / or oxygen resistant layer.

[0070] In embodiments where the contact layer is hygroscopic, the base layer is preferably made from a metal foil such as aluminum. Aluminum is price competitive and an excellent barrier against all gases and moisture. Further, like other metal-like materials, aluminum has good crease properties, i.e., it does not spread once folded, reflects radiant heat, and imparts a decorative appeal to the laminate and packaging.

[0071] Typically, especially when the base layer contains or is made of aluminum, the thickness of the base layer is 8 to 10 μm, such as 5 to 15 μm, preferably 7 to 12 μm, and more preferably 9 μm. When the base layer contains or is made of a polymer, such as PET, the thickness may be greater, for example, in the range of 1 to 50 μm.

[0072] According to the present invention, the contact layer, if present, must be chemically resistant / inert to APIs, such as so-called highly active substances and excipients that are ultimately packaged. Furthermore, the contact layer must exhibit low absorption of substances moving through the film or lamination. The acceptable level of absorption for a given substance is typically determined by the substance's manufacturer, but often the acceptable value is in the range of 0 to 1% (w / w). For some products, up to 10% (w / w) is acceptable for products that typically have a low initial API content. Absorption is calculated as the weight of API in the packaging after a set storage period for a particular product, relative to the initial weight of API in the marketed product. Typical shelf life is about 2 years, e.g., 18 months to 5 years.

[0073] It will be understood that the parameter reflecting the thickness of the contact layer depends on the method by which the laminate is formed, as is customary in the art. Therefore, for laminates formed by adhesive lamination or extrusion lamination, the parameter used to reflect the thickness of the contact layer is μm. For laminates in which at least one tie layer and a contact layer are co-extruded, the parameter used to define the contact layer and the tie layer is g / m 2 This is the amount of material to be loaded. A person skilled in the art can determine the thickness of each layer from the loading and density of the material used, as needed.

[0074] The contact layer preferably contains a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

[0075] The contact layer may also be a blend of one of the polymers defined above, combined with a lower polymer such as polyethylene (PE), a polyethylene blend, or other polymers known to those skilled in the art. In the case of a blend, the contact layer preferably or more preferably contains at least 50% (w / w) of COC, PA, EVOH, CBC, PVDF, COP, HDPE, or EMAA.

[0076] When films are bonded and laminated, the contact layer may also consist of two or more layers, including one or more tie layers. In such embodiments, the side of the contact layer facing away from the substrate may be indicated as the sealing layer, and the side of the contact layer facing the substrate may be indicated as the tie layer. When the contact layer and / or tie layer consist of two or more layers, these layers can be made by a suitable method such as co-extrusion.

[0077] According to all embodiments of the present invention, the contact layer may be made from a material selected from cyclic olefin copolymers, polyamides, ethylene vinyl alcohol, cyclic block copolymers, polyvinylidene fluoride, cyclic olefin polymers, high-density polyethylene, or ethylene-methacrylate copolymer (EMAA), or mixtures thereof, for example, the commercially available product EVAL® C109B sold by Kuraray, Selar PA 3426 R sold by Dupont®, or COC 6013M-07, COC 8007F-600, 7010F-600 or 9506F500 sold by Topas®, or EVOH available from Nippon Gohsei under the trademark name Soarnol®, and the COC film may be supplied by Amcor or Plastique Venthenat. Other examples include ViviOn 8210 (CBC) sold by USI Corporation, Kynar® 710 (PVDF) sold by Zeus Industrial Products, ZEONOR® 1420R (COP) sold by Zeon Specialty Materials, Inc., CG9620 or CG8410 (HDPE) sold by Borealis AG, and Surlyn® (EMAA) sold by Dupont®. Other variations of the same function are within the scope of the present invention.

[0078] Table 1 lists non-exclusive examples of commercially available polymers that can be used as contact layers according to the present invention. [Table 1]

[0079] Preferably, the contact layer consists of only one material, namely, a cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). Preferably, the contact layer is a single layer. More preferably, it is a single layer of one material. Despite the challenges associated with providing a single-component contact layer, this may be preferred to avoid scalping, as a PE-containing blend may permeate and thus result in a sieve-like layer over time.

[0080] It has been found that when the contact layer contains any of the polymers from the above group, chemical-resistant films and laminates can be obtained even with relatively low RED values, and even when the above polymers chemically represent different polymer types. Tests have shown that the resistance of laminates containing the preferred polymer is similar to or better than that of laminates coated / laminated with, for example, the commercially available product Barex®. RED values ​​or HSP parameters are parameters known to those skilled in the art, and further details can be found, in particular, in Hansen, C., M., Hansen Solubility Parameters a User's Handbook 2nd Ed., CRC Press, Boca Raton, 2007.

[0081] EVOH is typically used in lamination due to its excellent oxygen barrier properties and tear strength. Despite being known to be highly hydrophilic and hygroscopic (i.e., having a high WVTR), EVOH is very suitable as a contact layer according to the present invention.

[0082] Furthermore, polyamide (PA) has typically been used in lamination due to its excellent mechanical properties, such as tear strength, or as a barrier. Regarding EVOH, it is noteworthy that PA can be used as a contact layer to provide chemically resistant laminated films, despite its hydrophilicity.

[0083] Due to the hydrophilicity of PA and EVOH, in a preferred embodiment, the laminated film obtained according to the present invention may be tightly packed in a moisture barrier, especially if it must be stored. The laminated film according to the present invention may be packed immediately after manufacture and should remain safely packed, for example, on a filling line, until further use.

[0084] In some embodiments, the contact layer is made from a blend of at least two polymers. Using a blend can be a means of reducing costs and adapting the physical and chemical properties of the lamination process, for example, by lowering or raising the melting temperature to match the layer profile and the polarity of the blend, if present, to improve the adhesion properties of the layer and therefore the robustness of the final product.

[0085] In one variation, cyclic olefin copolymers, polyamides, ethylene vinyl alcohol, cyclic block copolymers, polyvinylidene fluoride, cyclic olefin polymers, high-density polyethylene, or ethylene-methacrylic acid copolymers (EMAA) constitute at least 50% w / w of the contact layer blend, preferably at least 60% w / w of the contact layer or each layer of the contact layer, more preferably at least 80% w / w, and most preferably at least 95% w / w. In this variation, the contact layer is a single layer or consists of two or more layers.

[0086] The tie layer may be selected from ethylene methacrylic acid (EMAA), ethylene acrylic acid (EAA), preferably ethylene acrylic acid (EEA-high acid) having a minimum acrylic acid content of 10% (W / W) based on the total weight of the ethylene acrylic acid layer, a terpolymer of ethylene, methacrylic acid and glycidyl methacrylate, a terpolymer of ethylene, acrylic acid ester and maleic anhydride, preferably ethylene, butyl acrylate and maleic anhydride (t-EBAMA), acrylic acid ester and maleic anhydride, preferably ethylene butyl acrylate, maleic anhydride (t-EBAMA), ethylene methyl acrylate (EMA), ethylene butyl acrylate (EBA), ethylene ethyl acrylate (EEA), low-density polyethylene (LDPE), metallocene compounds, or combinations thereof.

[0087] Preferably, the lamination according to the present invention further comprises a first outer layer preferably made from a material selected from, but not limited to, paper, polyethylene or polyamide sheets, or ortho-phthalaldehyde sheets, or polyester sheets, or combinations thereof, such as the commercially available F-PAP sold by Flexpet. When polyester sheets are used, the first outer layer is preferably a combination of materials.

[0088] Preferably, the first outer layer and the laminated film are laminated to provide packaging. Laminating the first outer layer onto the laminated film provides a strong lamination when tested with several parameters, and the packaging can be easily wrapped and sealed / welded.

[0089] Preferably, the laminated film further includes a second outer layer facing the outside of the first outer layer. Preferably, the second outer layer is a paper layer. The paper layer is typically printed with the product name, color and / or logo, as well as the manufacturer of the product. It is also or alternatively intended that the first outer layer may be printed. In some embodiments where the first outer layer is polyethylene, the laminated film further includes a second outer layer.

[0090] Adhesives and / or polymers may be applied between various layers. The adhesive and / or polymer used between the first outer layer and the base layer or the second outer layer may be made from the same or different materials as the adhesive used for the adhesive lamination of the base layer and the contact layer. Furthermore, the agent applied between these layers may be selected from a two-component adhesive extruded and laminated using a polymer or water-based adhesive selected from the group of materials used as tie layers according to the present invention, the latter being particularly useful when a paper layer is used.

[0091] Further preferred adhesives are those approved for use in packaging products for human use and are well known to those skilled in the art. Suitable adhesives may be selected from, but are not limited to, polyurethane adhesives, epoxy adhesives, or acrylic adhesives, all of which are well known to those skilled in the art.

[0092] According to all aspects and embodiments of the present invention utilizing adhesive lamination, the adhesive used for adhesive lamination is a two-component adhesive commonly known in the art. Thus, it is based on polyurethane and epoxy, for example, polyurethane and an aromatic or aliphatic amine. Exemplary commercially available polyurethane adhesives usable according to the present invention are LOCTITE LIOFOL LA 3644-21 MHS / LA 6055, available from Loctite®, or Adcote® 811A EA / MOR-FREE® 200C coreactate, available from Dow.

[0093] When the adhesive lamination is solvent-based, the solvent is appropriately selected from ethyl acetate, acetone, and methyl ethyl ketone, or other solvents well known to those skilled in the art.

[0094] When using, mix the solvent and the two-component adhesive in the specific ratio specified by the manufacturer in the usual manner. The substrate and curing agent are mixed in the ratio recommended by the adhesive supplier—typically 8:1 to 15:1 calculated based on solids content, but other ratios are also intended.

[0095] The solvent is added to yield a viscosity in the range of 15 to 22 seconds, for example, about 17 to 18 seconds, as measured by DIN CUP 4, a method well known to those skilled in the art under the DIN 53211 standard.

[0096] Conveniently, most of the polymers, adhesives, and other components usable in this method are conventional and therefore readily available from various suppliers, thereby providing cost-effective production.

[0097] This method further involves the following steps. a) optionally providing a first and / or second outer layer. b) Step of providing a laminated film according to the present invention c) A step of placing a composition containing the compound on the contact layer side of the laminated film. d) A step of sealing the outer layer and / or laminated film, preferably by heat fusion, to provide a hollow internal space for sealing the composition, wherein the hollow space has an inner and an outer side, the inner side of the film being the contact layer of the adhesive lamination and the outer side of the film being the base layer and / or the first and second outer layers. The first and / or second outer layers are intended to be laminated onto the laminated film in, for example, one combined lamination step prior to steps c) and d).

[0098] In general, the order in which the different layers of the packaging according to the present invention are applied to the base layer is flexible. Therefore, the first outer layer may be applied before adhesive lamination, or vice versa. The order depends on which production line is appropriate in the particular situation.

[0099] Furthermore, according to the present invention, laminated films and packaging produced according to this method can be obtained.

[0100] According to the present invention, the laminated film according to the present invention has various applications. In one embodiment of the present invention, the laminated film is used to enclose a composition comprising a compound selected from nicotine, fentanyl, lidocaine, and rivastigmine, preferably the compound being formulated as a patch such as a transdermal patch.

[0101] According to the present invention, when the composition is a patch, the amount of active ingredient remaining after storage at 40°C for at least 7 days is at most + / - 10% (w / w) compared to the same active ingredient sealed in a similar Barex® patch as index 100.

[0102] According to the present invention, the resulting laminated film is heat-sealable or weldable. A heat-sealable laminated film can seal itself during heat sealing without deformation. Deformation is undesirable in terms of quality assurance and must be carefully described, which is very labor-intensive. Furthermore, laws in many countries are very strict. Therefore, films and / or laminates that have deformation cannot be filled with active ingredients. Thus, mechanical properties are very important from the viewpoint of manufacturing cost efficiency. Similarly, it is important that the laminate is tightly packed.

[0103] The laminated film obtained in the present invention must be inert and impermeable to the compound encapsulated in the laminate. Accordingly, in one embodiment of the present invention, after storage at 40°C for 12 weeks, up to 10% (w / w), preferably up to 5% (w / w), more preferably up to 1.5% (w / w), and most preferably up to 0.5% (w / w) of the compound migrated into the laminated film.

[0104] The laminated film of the present invention can appropriately encapsulate compositions or compounds containing active ingredients selected from the group consisting of nicotine, rivastigmine, fentanyl, and lidocaine. These active ingredients are known as highly active chemicals / compounds and require special packaging.

[0105] The packaging should preferably conform to international standards such as ISO 8317 (2003), which corresponds to 16 CFR §1700.20 (for the United States) and DIN EN ISO 8317 (2004) (for Europe). In the context of the present invention, “packaging” is intended to mean a complete laminated film, optionally including a first and / or second outer layer used for filling the compound.

[0106] The sealing of the packaging is achieved in such a manner that the contact layer of the laminated film faces the compound or composition, so that the rest of the packaging is protected by the contact layer. In this way, the compound or composition is held inside the packaging and is therefore only in direct contact with the contact layer of the laminated film layer.

[0107] The following are specific, non-limiting embodiments of the present invention that demonstrate favorable characteristics.

[0108] Adhesive lamination example: A specific laminated film having COC as a contact layer: 1) Paper / Adhesive / Aluminum / Adhesive / COC 2) PET / adhesive / aluminum / adhesive / COC 3) Paper / Adhesive / Aluminum / Adhesive / OPA / Adhesive / COC 4) Paper / 3g adhesive / PET 23μm / 3g adhesive / Aluminum / Adhesive / COC

[0109] More specifically: 1) Paper 50gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / COC 20μm 2) PET 36μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / COC 20μm 3) Paper 40gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / oPA 15μm / Adhesive 3g / COC 20μm 4) Paper 40gsm / Adhesive 3g / PET 23μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / COC 20μm

[0110] A specific laminated film having PA as a contact layer: 1) Paper / Adhesive / Aluminum / Adhesive / PA 2) PET / adhesive / aluminum / adhesive / PA 3) Paper / Adhesive / Aluminum / Adhesive / OPA / Adhesive / PA 4) Paper / adhesive / PET / adhesive / aluminum / adhesive / PA.

[0111] More specifically: 1) Paper 50gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / PA 40μm 2) PET 23μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / PA 40μm 3) Paper 40gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / PA 15μm / Adhesive 3g / PA 40μm 4) Paper 40gsm / Adhesive 3g / PET 23μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / PA 40μm

[0112] A specific laminated film having EVOH as a contact layer: 1) PET / PE / Aluminum / Adhesive / EVOH 2) Paper / Adhesive / Aluminum / Adhesive / EVOH 3) PET / adhesive / aluminum / adhesive / EVOH 4) Paper / Adhesive / Aluminum / Adhesive / OPA / Adhesive / EVOH 5) Paper / Adhesive / PET / Adhesive / Aluminum / Adhesive / EVOH

[0113] More specifically: 1) PET 50μm / PE 14g / Aluminum 9μm / Adhesive 3g / EVOH 30μm 2) Paper 50 gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / EVOH 30μm 3) PET 36μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / EVOH 30μm 4) Paper 40 gsm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / oPA 15μm / Adhesive 3g / EVOH 30μm 5) Paper 40gsm / Adhesive 3g / PET 23μm / Adhesive 3g / Aluminum 9μm / Adhesive 3g / EVOH 30μm

[0114] Example 1: Example of adhesive lamination strength The present invention will be described in more detail with reference to the following non-limiting examples that test the sealing strength of laminated films that exemplify the present invention. In all embodiments, the sealing strength was measured using the DIN 55529 standard.

[0115] A laminated film having 100% COC as a single-contact layer is This product, fabricated by adhesive lamination using a two-component solvent urethane adhesive, contains PET 23μm / adhesive / al 9μm / adhesive / COC 20μm.

[0116] Laminated film 0.5 N / mm 2 The seal was then sealed for 0.5 seconds. The seal strength obtained in the temperature range of 120 to 190°C was 10 to 15 N / 15 mm. This strength is equivalent to a similar Barex® laminate with a 20 to 25 micron Barex® layer instead of COC.

[0117] A film having 100% cast PA as a single contact layer, This product contains PET 23μm / adhesive / al 9μm / adhesive / CPA 40μm, fabricated by adhesive lamination using a two-component solvent urethane adhesive.

[0118] Laminated film 0.5 N / mm 2 The film was sealed for 0.5 seconds. The sealing strength obtained in the temperature range of 150 to 200°C was 25 to 40 N / 15 mm. This strength is equivalent to that of a similar Barex® laminate with a 50 micron Barex® layer, which means that a laminate with PA as the contact / seal layer provides a higher sealing strength than Barex®, even with a lower film thickness of the contact / seal layer.

[0119] A film having 100% EVOH as a single contact layer, This product is manufactured by adhesive lamination using a two-component solvent urethane adhesive and contains PET 50μm / PE 12gsm / al 9μm / adhesive / EVOH 30μm.

[0120] Laminated film 0.5 N / mm 2 The film was sealed for 0.5 seconds. The sealing strength obtained in the temperature range of 150 to 200°C was 25 to 40 N / 15 mm. This strength is equivalent to that of a similar Barex® laminate with a 50 micron Barex® layer. Therefore, the EVOH film provides the same sealing strength despite having a thinner sealing layer, which also means that a higher sealing strength than Barex® can be obtained if desired.

[0121] Example 2: RED&CHI values

[0122] Tests were conducted to determine the RED and CHI values ​​of PVDF, HDPE, and EMAA samples for a certain range of chemical species.

[0123] RED calculation

[0124] Determining the HSP value and interaction radius requires that the solubility of the drug be evaluated in at least 16 solvents having a certain range of polarity and hydrogen bonding properties. The methodology for determining the HSP value, interaction radius, and RED value is described in CMHansen: "Hansen Solubility Parameters, A User's Handbook", CRC Press, 2007, Second Edition, and is illustrated in EP2895531.

[0125] To evaluate solubility, each sample was first weighed in a standard test tube, and an aliquot of the screening solvent was added. The test tubes were then placed on a rotating stand for 24 hours, and the presence or absence of dissolution / swelling of the sample was visually confirmed.

[0126] A score of 1 is given if the sample is soluble; a score of 2 is given if the sample swells; and a score of 3 is given if the sample is not soluble.

[0127] When solubility is plotted in Hansen space (3-dimensional: δD = dispersion parameter / δP = polarity parameter / δH = hydrogen bonding parameter), where 1 = soluble, 2 = swelling, and 3 = insoluble, the solubility domain can be calculated using a fitting algorithm. The relevant parameters for PVDF, HDPE, and EMAA are summarized in Table 2, and the test results are shown in Table 3. [Table 2]

[0128] Table 3 shows the RED and CHI values ​​for samples relating to the range of chemical species. [Table 3]

[0129] It will be understood that the RED value reflects the experimental determination of R, while CHI represents a theoretical determination based on the volume of API.

[0130] APIs with both RED and CHI values ​​greater than 1 are considered very suitable for packaging in films facing a contact layer, while APIs with one of RED or CHI (typically the CHI value) less than 1 are considered less suitable. APIs with both RED and CHI less than 1 are considered even less suitable for packaging in films having the contact layer in question.

[0131] As can be seen from both experiments and theoretical calculations, the tested contact layer has broad applicability as a contact layer for APIs (values ​​less than 1 are in italics).

[0132] Example 3: Strength of the co-extrusion example:

[0133] Mechanical properties were tested. Different laminated films, including both the outer and base layers, were fabricated to mimic commercially available products. The laminated films were manufactured using different applications of the co-extruded material, as shown in Table 4.

[0134] All laminated films were fabricated with PET23 / AL9 having co-extruded HDPE as follows: Tie layer 2: Nucrel(registered trademark) 0609HSA (ethylene methacrylic acid) Thai layer 1: PE MI15 (PE, e.g., Borealis® CA9150) Contact layer: Borealis® CG9620 (HDPE) [Table 4] As can be seen, there was a discrepancy between the target load and the actual load. In reality, the discrepancy is thought to be due to the Thai layer's load being lower than the target value.

[0135] method: The mechanical properties of the laminated films shown in Table 4 were tested. In particular, the following characteristics were tested: -Tear strength -Puncture resistance (front side) -Sealing strength - Lamination strength - Exploration test

[0136] All tests are conducted in accordance with industry standards, with some modifications as detailed below: Tear strength - No change, in accordance with ASTM D1938-14.

[0137] Puncture resistance - In accordance with ASTM F1306, the following modifications are made: the sample diameter is 48 mm instead of 34.9 mm, and the lancet tip diameter is 3.0 mm instead of 3.2 mm.

[0138] Sealing strength remains unchanged, in accordance with DIN55529. The sealing strength test was performed under the following conditions: 160°C, 500N pressure, 0.5 seconds.

[0139] The lamination strength was adjusted according to ASTM D903-98 (2010), with the following modifications: the sample width was 15 mm instead of 25 mm, and the samples were not adjusted to 23°C ± 1°C and 50% RH ± 2%. Instead, all samples were kept in the same location and therefore continuously maintained under identical conditions. The tensile speed was set to 100 mm / min instead of 305 mm / min. The measured angle was 90°, not 180°.

[0140] The exploration strength test was performed as follows: A four-sided sealed bag was sealed to a size of 80 mm × 90 mm, including a 5 mm wide sealing area, under the parameters of 160°C, 0.5 seconds, and a pressure of 500 N.

[0141] The bag was held and punctured with a syringe connected to a pressure device. Then, in one test (Exploratory Test 1), the bag was inflated to a pressure of 0.2 bar, and in another test (Exploratory Test 2), it was inflated to a pressure of 0.25 bar. The success criterion for the predetermined stacking was to suppress the pressure for 30 seconds without rupture.

[0142] The results of all the tests conducted are shown in Table 5. [Table 5]

[0143] Consider The tear strength levels range from 1.5 to 6.1 N. The results indicate that the main influence on tear strength is the thickness of the contact layer, rather than the thickness of the tie layer or the total thickness of the co-extruded layer.

[0144] When considering puncture resistance, samples 1 through 9 exhibited puncture resistance ranging from 36.7N to 46.4N (front side). This represents only an increase of approximately 22%, even when the coating weight increased fourfold from the minimum to the maximum load. This indicates that the substrate is the primary factor influencing puncture resistance.

[0145] When attempting to separate the co-extruded material, all samples tore, making it impossible to measure the lamination strength. This indicates that, under all circumstances, the adhesion level of the co-extruded material is greater than the tear strength of the co-extruded material.

[0146] Regarding sealing strength, the results clearly show an increase in sealing strength following an increase in the loading of the contact layer portion of the co-extruded material. However, when the loading of the tie layer becomes too low, 3 g / m² per layer. 2 It can also be seen that the sealing strength decreases sharply in this region. This is observed in sample 1, which has a sealing strength of 7.3 N / 15 mm, and sample 5, which has a sealing strength of 12.9 N / 15 mm.

[0147] Sample 1 is 7.4 g / m 2 It has a contact layer loading, which is almost the same as sample 2, but sample 2 has significantly higher sealing strength. Sample 5 has 14 g / m 2 It has a contact layer loading of 12g / m 2 It has lower sealing strength than sample 4, which has a contact layer loading. The target layer distribution is 20 g / m². 2 Even so, the measured total load of sample 5 was 17 g / m³. 2 Please note that this was the case. This means that the loading of the Thai layer was actually 3g / m³. 2 This indicates that it is less than , which explains the difference.

[0148] This was also confirmed in exploration tests where samples 1 and 5 could not withstand the internal pressure, at 3 g / m³. 2 This indicates that a tie-layer loading exceeding a certain value is important in at least some situations to achieve the desired characteristics.

[0149] item

[0150] Item "A" relates to adhesive lamination. A1 A method for providing a laminated film, i) A step of providing a base layer that is water-resistant and / or oxygen-resistant, ii) The step of providing a contact layer, iii) preferably a step of laminating the base layer onto the contact layer by adhesive lamination or extrusion lamination, The method wherein the contact layer comprises a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). A2 The method according to item A1, wherein the contact layer is a polymer selected from the group consisting of cyclic olefin copolymer, polyamide, ethylene vinyl alcohol, cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). A3 The method according to item A1 or A2, wherein the contact layer is a single layer. A4 The method according to any one of items A1 to A3, wherein the lamination is an adhesive lamination, and in particular a solvent-based adhesive lamination. A5 The adhesive used for adhesive lamination is a two-component adhesive based on polyurethane and an aromatic or aliphatic amine, preferably with ethyl acetate as the solvent, as described in item A4. A6 The lamination is an extrusion lamination, according to any one of items A1 to A3. A7 The method according to item A6, wherein the extruded laminate uses a copolymer made of a material selected from a copolymer of ethylene and acrylic acid, a copolymer of ethylene and methacrylic acid, and a terpolymer comprising ethylene, an acrylic acid ester and a third polymer, wherein the third polymer is preferably glycidyl methacrylate, more preferably maleic anhydride, or alternatively the extruded laminate uses PMMA. A8 The method according to any one of items A1 to A7, wherein the base layer is laminated to at least a first outer layer, preferably the first outer layer comprising polyethylene terephthalate (PET), polyethylene (PE), paper, or a combination thereof. A9 The method according to any one of items A1 to A8, wherein the contact layer is a polyamide, and the side of the polyamide layer facing away from the base layer contains an amorphous polyamide. A10 The method according to item A9, wherein an amorphous polyamide layer and a polyamide layer are co-extruded. A11 The side of the contact layer facing the base layer is corona treated, as described in item A8 or A9. A12 The amorphous PA layer constitutes 10 to 40% of the thickness of the contact layer, according to any one of items A9 to A11. A13 The method according to any one of items A1 to A8, wherein the contact layer contains or consists of COC. A14 The method according to item A13, wherein the contact layer contains COC, with a COC content of at least 40% (w / w), or the contact layer is a co-extruded product of COC and a tie layer. A15 The COC layer is corona-treated according to the method described in item A13 or A14. A16 The COC layer has a thickness of 18 to 22 μm, preferably 20 μm, according to any one of items A13 to A15. A17 The method according to any one of items A1 to A8, wherein the contact layer is ethylene vinyl alcohol, and the EVOH layer has a thickness of 25 to 35 μm, preferably 30 μm. A18 The method according to any one of items A1 to A8, wherein the contact layer comprises or is a cyclic block copolymer, and the layer has a thickness of 20 to 60 μm. A19 The method according to any one of items A1 to A8, wherein the contact layer contains or is polyvinylidene fluoride, and the layer has a thickness of 15 to 50 μm. A20 The method according to any one of items A1 to A8, wherein the contact layer comprises or is a cyclic olefin polymer, and the layer has a thickness of 20 to 60 μm. A21 The method according to any one of items A1 to A8, wherein the contact layer contains or is made of high-density polyethylene, and the layer has a thickness of 15 to 60 μm. A22 The method according to any one of items A1 to A8, wherein the contact layer comprises or is an ethylene-methacrylic acid copolymer, and the layer has a thickness of 15 to 50 μm. A23 The method according to any one of items A1 to A8, wherein the contact layer comprises or is a polyamide, and the layer has a thickness of 15 to 60 μm. A24 The method according to any one of items A1 to A23, wherein the laminated film encloses the composition, and the laminated film is sealed in a pouch, sachet, or used as a lid film on a container. A25 The method according to any one of items A1 to A24, further comprising the step of laminating at least a first outer layer on the base layer side of the laminated film. A26 The method according to any one of items A1 to A25, wherein the thickness of the laminated film is in the range of 70 to 140 μm. A27 A laminated film comprising at least one base layer which is water-resistant and / or oxygen-resistant, and a contact layer bonded to the base layer, wherein the contact layer contains or is composed of a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). A28 The contact layer is bonded to the base layer, and the laminated film is as described in item A27. A29 A laminated film according to item A27, obtained by any one of the methods described in items A1 to A26. A30 A highly active chemical substance filled into a laminated film, wherein the laminated film is one of the items A27, A28, or A29. A31 The highly active chemical substance is selected from the group consisting of nicotine, fentanyl, lidocaine, and rivastigmine, and is filled into the laminated film described in item A30. A32 Use of polymers selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), or high-density polyethylene (HDPE) or ethylene-methacrylate copolymers (EMAA) in the contact layer of films for packaging highly reactive chemicals.

[0151] Item "B" relates to co-extrusion. B1 A method for providing a laminated film, i) A step of providing a base layer that is water-resistant and / or oxygen-resistant, ii) The step of providing a contact layer, iii) A step of coating the base layer with a co-extruded layer, wherein the co-extruded layer includes the contact layer and the tie layer, iv) a step that enables bonding the co-extruded layer and the base layer, A method comprising a contact layer containing a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). B2 The Thai layer has the following: b) Each layer must be loaded at least 3g / m³ 2 is, or, b) Loading of multiple layers, at least one of the layers, must be at least 3g / m³ 2 The total load of multiple layers is at least 3g / m³ 2 The method described in item B1. B3 The method according to item B1 or B2, wherein the contact layer is a polymer selected from the group consisting of cyclic olefin copolymer, polyamide, ethylene vinyl alcohol, cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). B4 The method according to any one of items B1 to B3, wherein the contact layer is a cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylate copolymer (EMAA). B5 The contact layer has a minimum of 5 g / m² 2Preferably at least 10 g / m 2 A method according to any one of items B1 to B4, having a load. B6 The aforementioned tie layer is made up of 1, 2, 3, 4, or 5 layers, according to any one of the methods described in items B1 to B4. B7 The method according to item B6, wherein all layers of the tie layer are co-extruded with the contact layer. B8 The method according to any one of items B1 to B7, wherein the co-extruded layer is co-extruded onto the substrate layer. B9 The method according to any one of items B1 to B8, wherein the tie layer consists of one layer, the layer being a copolymer made of a material selected from an ethylene-acrylic acid copolymer, an ethylene-methacrylic acid copolymer, and a terpolymer comprising ethylene, an acrylic acid ester, and a third polymer, the third polymer being preferably glycidyl methacrylate, more preferably maleic anhydride. B10 The method according to any one of items B1 to B8, wherein the tie layer comprises at least two layers, the first layer comprising the copolymer described in item B8, and at least the second or more layers comprising a material selected from EEA, PE, EMA, EAA, or a combination thereof. B11 The method according to any one of items B1 to B10, wherein the contact layer is a polyamide, and the side of the polyamide layer facing away from the base layer contains an amorphous polyamide. B12 The method according to any one of items B1 to B11, wherein the laminated film encloses the composition, and the laminated film is sealed in a pouch or sachet, or used as a lid film on a container. B13 The method according to any one of items B1 to B12, further comprising the step of laminating at least a first outer layer on the base layer side of the laminated film. B14 The method according to any one of items B1 to B13, wherein the total thickness of the laminated film is in the range of 70 to 140 μm. B15 A laminated film comprising at least one base layer which is water-resistant and / or oxygen-resistant, and a co-extruded layer, wherein the co-extruded layer comprises a tie layer and a contact layer, and the contact layer comprises or comprises a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA). B16 A laminated film according to item B15, obtained by the method of any one of items B1 to B14. B17 The laminated film is a highly reactive chemical substance filled into the laminated film, as described in either item B15 or B16. B18 The highly active chemical substance is selected from the group consisting of nicotine, fentanyl, lidocaine, and rivastigmine, and is a highly active chemical substance filled into the laminated film described in item B17. B19 Use of polymers selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), or high-density polyethylene (HDPE) or ethylene-methacrylate copolymers (EMAA) in the contact layer of films for packaging highly reactive chemicals. B20 The use described in item B19, comprising a base layer, a tie layer, and a contact layer, wherein the contact layer and the tie layer are co-extruded coatings on the base layer.

Claims

1. A method for providing a laminated film, i) A step of providing a base layer that is water-resistant and / or oxygen-resistant, ii) The step of providing a contact layer, iii) A step of coating the base layer with a co-extruded layer, wherein the co-extruded layer includes the contact layer and the tie layer, iv) a step that enables bonding the co-extruded layer and the base layer, The method wherein the contact layer comprises a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

2. The Thai population a) One layer, the loading of the one layer is at least 3 g / m ２ is, or, b) Multiple layers, with at least one of the layers being loaded at least 3 g / m² ２ The total load of the multiple layers is at least 3 g / m ２ The method according to claim 1, wherein the method is having the following characteristics.

3. The method according to claim 1 or 2, wherein the contact layer is a polymer selected from the group consisting of cyclic olefin copolymer, polyamide, ethylene vinyl alcohol, cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

4. The method according to any one of claims 1 to 3, wherein the contact layer is a cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

5. The contact layer has a density of at least 5 g / m². ２ Preferably at least 10 g / m ２ The method according to any one of claims 1 to 4, comprising loading of a

6. The method according to any one of claims 1 to 4, wherein the tie layer is made of 1, 2, 3, 4, or 5 layers.

7. The method according to claim 6, wherein all layers of the tie layer are co-extruded with the contact layer.

8. The method according to any one of claims 1 to 7, wherein the co-extruded layer is co-extruded onto the base layer.

9. The method according to any one of claims 1 to 8, wherein the tie layer is composed of one layer, the layer being a copolymer made of a material selected from an ethylene-acrylic acid copolymer, an ethylene-methacrylic acid copolymer, and a terpolymer comprising ethylene, an acrylic acid ester, and a third polymer, the third polymer being preferably glycidyl methacrylate, more preferably maleic anhydride.

10. The method according to any one of claims 1 to 8, wherein the tie layer comprises at least two layers, the first layer comprising the copolymer described in claim 8, and at least the second or more layers comprising a material selected from EEA, PE, EMA, EAA, or a combination thereof.

11. The method according to any one of claims 1 to 10, wherein the contact layer is a polyamide, and the side of the polyamide layer facing away from the base layer contains an amorphous polyamide.

12. The method according to any one of claims 1 to 11, wherein the laminated film encloses a composition, and the laminated film is sealed in a pouch or sachet, or used as a lid film on a container.

13. The method according to any one of claims 1 to 12, further comprising the step of laminating at least a first outer layer on the base layer side of the laminated film.

14. The method according to any one of claims 1 to 13, wherein the total thickness of the laminated film is in the range of 70 to 140 μm.

15. A laminated film comprising at least one base layer which is water-resistant and / or oxygen-resistant, and a co-extruded layer, wherein the co-extruded layer comprises a tie layer and a contact layer, and the contact layer comprises or comprises a polymer selected from the group consisting of cyclic olefin copolymer (COC), polyamide (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymer (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymer (COP), high-density polyethylene (HDPE), or ethylene-methacrylic acid copolymer (EMAA).

16. A laminated film according to claim 15, obtained by the method described in any one of claims 1 to 14.

17. The laminated film is a highly active chemical substance filled into the laminated film as described in any one of claims 15 or 16.

18. The highly active chemical substance is selected from the group consisting of nicotine, fentanyl, lidocaine, and rivastigmine, and is a highly active chemical substance filled into the laminated film according to claim 17.

19. Use of polymers selected from the group consisting of cyclic olefin copolymers (COC), polyamides (PA), ethylene vinyl alcohol (EVOH), cyclic block copolymers (CBC), polyvinylidene fluoride (PVDF), cyclic olefin polymers (COP), or high-density polyethylene (HDPE) or ethylene-methacrylic acid copolymers (EMAA) in the contact layer of films for packaging highly reactive chemicals.

20. The use according to claim 19, comprising a base layer, a tie layer, and a contact layer, wherein the contact layer and the tie layer are co-extruded coated onto the base layer.

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