WO2022148848A1 - Films stratifiés destinés à être utilisés dans des récipients pour formes posologiques orales solides, ainsi que leur utilisation et leur préparation - Google Patents

Films stratifiés destinés à être utilisés dans des récipients pour formes posologiques orales solides, ainsi que leur utilisation et leur préparation Download PDF

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Publication number
WO2022148848A1
WO2022148848A1 PCT/EP2022/050288 EP2022050288W WO2022148848A1 WO 2022148848 A1 WO2022148848 A1 WO 2022148848A1 EP 2022050288 W EP2022050288 W EP 2022050288W WO 2022148848 A1 WO2022148848 A1 WO 2022148848A1
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layer
contact layer
container
packaged product
laminate film
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PCT/EP2022/050288
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English (en)
Inventor
Torben FOGTMANN
Peter Johansen
Lars Christian Christensen
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Danapak Flexibles A/S
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Publication of WO2022148848A1 publication Critical patent/WO2022148848A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B7/00—Layered products characterised by the relation between layers; Layered products characterised by the relative orientation of features between layers, or by the relative values of a measurable parameter between layers, i.e. products comprising layers having different physical, chemical or physicochemical properties; Layered products characterised by the interconnection of layers
    • B32B7/04—Interconnection of layers
    • B32B7/12—Interconnection of layers using interposed adhesives or interposed materials with bonding properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B15/00—Layered products comprising a layer of metal
    • B32B15/04—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B32B15/08—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
    • B32B15/085—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin comprising polyolefins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B15/00—Layered products comprising a layer of metal
    • B32B15/20—Layered products comprising a layer of metal comprising aluminium or copper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/30—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers
    • B32B27/304—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers comprising vinyl halide (co)polymers, e.g. PVC, PVDC, PVF, PVDF
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/30—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers
    • B32B27/306—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers comprising vinyl acetate or vinyl alcohol (co)polymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/30—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers
    • B32B27/308—Layered products comprising a layer of synthetic resin comprising vinyl (co)polymers; comprising acrylic (co)polymers comprising acrylic (co)polymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/32—Layered products comprising a layer of synthetic resin comprising polyolefins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/32—Layered products comprising a layer of synthetic resin comprising polyolefins
    • B32B27/325—Layered products comprising a layer of synthetic resin comprising polyolefins comprising polycycloolefins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/34—Layered products comprising a layer of synthetic resin comprising polyamides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00—Layered products comprising a layer of synthetic resin
    • B32B27/36—Layered products comprising a layer of synthetic resin comprising polyesters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/30—Properties of the layers or laminate having particular thermal properties
    • B32B2307/31—Heat sealable
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/50—Properties of the layers or laminate having particular mechanical properties
    • B32B2307/58—Cuttability
    • B32B2307/581—Resistant to cut
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/50—Properties of the layers or laminate having particular mechanical properties
    • B32B2307/582—Tearability
    • B32B2307/5825—Tear resistant
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/70—Other properties
    • B32B2307/718—Weight, e.g. weight per square meter
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/70—Other properties
    • B32B2307/724—Permeability to gases, adsorption
    • B32B2307/7242—Non-permeable
    • B32B2307/7244—Oxygen barrier
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2307/00—Properties of the layers or laminate
    • B32B2307/70—Other properties
    • B32B2307/73—Hydrophobic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2439/00—Containers; Receptacles
    • B32B2439/40—Closed containers
    • B32B2439/46—Bags
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2439/00—Containers; Receptacles
    • B32B2439/80—Medical packaging

Definitions

  • Laminate films for use in containers for solid oral dosage forms as well as their use and preparation
  • the present invention relates to containers sealed with laminate films whereby a coextrusion layer comprising a contact layer and at least one tie layer is adhered to a base layer comprising a metal, using induction welding and containing active ingredients, where the contact layer is COC, PA, EVOH, CBC, PVDF, COP, HDPE, PP, PET or EMAA and the container is made of the same material as the contact layer.
  • the requirements of a packaged product with a film or laminate are typically: mechanically stable laminate that does not separate or deform;
  • a commercially used polymer that fulfils some or all of the require ments of extreme chemical resistance and inert properties is a polyacrylonitrile (PAN) based film, which is sold for example as resins under the trademark Barex®, which is manufactured i.a. by the company Ineos. Barex® is widely used and approved for drugs and food applications and is used because it is a good barrier towards oxygen, nitrogen and carbon dioxide compared to other common polymers, and because it has excellent chemical resistance towards different functional groups such as hydrocarbons, ketones, esters, alcohols, bases and acids and/or pharmaceuticals such as nicotine.
  • PAN polyacrylonitrile
  • Barex® resin is heat stable and therefore weldable at a temperature around 160 - 220°C, which makes it suitable for use in most applications of flexible packaging.
  • Barex® is sold at a high price due to the difficulties in its production and subsequent extrusion to a film which results in a high loss of material.
  • the water and oxygen resistance of Barex® is not satisfactory for all purposes.
  • WO 2017/114922 discloses a laminate film having a co-extrusion or co-extrusion coated layer comprising a tie layer and a contact layer, said contact layer is the innermost layer facing an aggressive chemical pharmaceutical such as ri- vastigmine, nicotine, fentanyl or lidocaine.
  • the contact layer may comprise polyamide, cyclic olefin copolymer, or an ethylene vinyl alcohol.
  • the tie layer is co-extrusion coated to a base layer so that the tie layer is in contact with the base layer and the contact layer.
  • a further solution is described in WO 2015/123211 disclosing a film having a tie layer and a contact layer comprising COC and PE blends facing a pharmaceutical such as nicotine.
  • the film may be produced by providing a co extrusion layer or by adhesive lamination.
  • the obtained laminate film is heat sealable or weldable, and is induction weldable by virtue of the base layer comprising metal.
  • Induction welding is an unusual method used for polymers, e.g. HDPE, seal layers due to the formation of heat generated from the aluminium, which may deteriorate the polymers and possibly the product, here the active ingre trans, packaged. It is therefore unexpected that strong laminates were ob tained without deteriorating the polymers.
  • a heat sealable laminate film is ca pable of sealing to itself during heat sealing without creating any deformation. Deformation is undesirable in relation to quality assurance, and some produc ers place restrictions on the extent to which films and/or laminates with any deformation are allowed for packing. Therefore, the mechanical properties are very important from a production cost efficiency perspective. Similarly, it is important that the laminates are tight and do not allow scalping.
  • coextrusion coating for sealing containers provides a better pro tection to the base layer, comprising metal, e.g. aluminium, compared to using welding lacquer/sealing lacquer since the risk of pin holes (small holes in the lacquer) is minimized when using coextrusion coated films to a container.
  • the sealing layer (contact layer) according to the invention is of the same material as the container to which it is to be welded, an increased inertness to the contained active ingredient is obtained as compared to con tainers typically sealed with PE or PE-copolymer based sealing layers. Moreo ver, when the sealed layers are made of the same material, a permanent seal ing is obtained between the container and the film or lid in the sense that a higher pressure resistance is obtained between the container, the film and the lid, as compared to traditionally welded films based on PE or PE-copolymer. In these traditional solutions there is a tendency for instability towards overpres sure between the container and the lid. Such overpressure in the container can occur if the container is subjected to external pressure higher than atmospheric but also if subjected to pressure drops, such as in airplanes and when trans porting at higher altitudes.
  • the film is produced by coextrusion coating.
  • coextrusion coating there is no need for adhesives in between the contact/seal layer and the base layer, such as aluminium, which is of benefit for particularly very aggressive active ingredients in order to prevent reaction and migration, but, also and more importantly when manufacturing at high temperatures.
  • the tie layer which ties the contact/seal layer together with the base layer, is a thermoplastic polymer, which becomes soft and sticky when welded (during the heating), but solidifies when cooled and regains the same or better binding than before the welding. PE-copolymers as tie layer will result in particularly improved bonding after welding.
  • the contact layer comprises or is HDPE.
  • HDPE is a material frequently used for containers for active ingredients in solid oral dosage forms. Being able to produce a complete package of the same material that meets the safety requirements and has at least the same strength as prior art solutions poses a significant benefit in terms of simplified chemistry and production.
  • the solid oral dosage form may have the form of a pill, tablet, capsule, gel capsule, lozenge or the like, the dosage form may be coated or uncoated.
  • the laminate is welded directly to the container. This config uration is simple and requires less chemistry and is therefore likely to be more inert and the strength of the sealing more robust.
  • the metal of the base layer is aluminium and more preferred that the base layer is aluminium.
  • the tie layer has: a) one layer and the loading of the one layer is at least 3 g/m 2 , or b) a plurality of layers and the loading of at least one layer of the plurality of layers is at least 3 g/m 2 , or the total loading of the plurality of layers is at least 3 g/m 2 .
  • the contact layer consists of one substance which is a polymer selected from the group consisting of a cyclic olefin copol ymer, a polyamide, an ethylene vinyl alcohol a cyclic block copolymer, a poly- vinylidene fluoride, a cyclic olefin polymer, a high density polyethylene, a pol ypropylene (PP), a polyethylene terephthalate (PET) or an ethylene-meth- acrylic acid copolymer and physical variations of thereof.
  • a polymer selected from the group consisting of a cyclic olefin copol ymer, a polyamide, an ethylene vinyl alcohol a cyclic block copolymer, a poly- vinylidene fluoride, a cyclic olefin polymer, a high density polyethylene, a pol ypropylene (PP), a polyethylene terephthalate (PET) or an ethylene-meth- acrylic acid copo
  • the contact layer may comprise or consist of a polymer selected from the group consisting of a cyclic block copolymer (CBC), a polyvinylidene fluo ride (PVDF), a cyclic olefin polymer (COP), a high density polyethylene (HDPE), a polypropylene (PP), a polyethylene terephthalate (PET) or an ethylene-meth- acrylic acid copolymer (EMAA).
  • CBC cyclic block copolymer
  • PVDF polyvinylidene fluo ride
  • COP cyclic olefin polymer
  • HDPE high density polyethylene
  • PP polypropylene
  • PET polyethylene terephthalate
  • EEMAA ethylene-meth- acrylic acid copolymer
  • the contact layer may have a loading of at 3 g/m 2 ' preferably at least 5 g/m 2 , more preferred at least 10 g/m 2 .
  • the tie layer is made of 1, 2, 3, 4 or 5 layers.
  • all the layers of the tie layer are coextruded with the contact layer.
  • the co-extrusion layer is preferably co-extrusion coated to the base layer.
  • the tie layer is constituted of one layer and the layer is a polyethylene copolymer.
  • the tie layer comprises at least two layers, wherein the first layer comprises a copolymer according to the above and the at least second or more layer(s) comprises a material selected from EEA, PE, EMA, EAA or a combination.
  • the tie layer or at least one layer of a plurality of tie layers may comprise or consist of PMMA.
  • PMMA is Plexiglas® HFI7.
  • Such tie layers may be particularly beneficial when the contact layer comprises or consists of PVDF, especially in extrusion coating.
  • the PMMA is pure.
  • the contact layer is polyamide.
  • the layer for example the polyamide layer, is amorphous.
  • a portion of the layer may be amorphous, for ex ample 10 to 40% (w/w).
  • the invention further comprises the step of laminating at least a first outer layer to the base layer side of the laminate film.
  • the total thickness of the laminate film may be in the range of 30 to 140 pm, such as 40-100 pm.
  • the active ingredient can be any substance suitable as a solid oral dosage form.
  • it could be selected from lidocaine, amphetamine, testosterone, fentanyl, oxymorphone, tetrahydro-cannabiol, rivastigmine, nic otine, diclofenac, dexibuprofen, NSAIDs, like ibuprofene and Dicofenac, para cetamol, aspirin, amino acids, such as leucine, penicillins, such as primcillin, Dl-camphor, dextromethorphan, ondansetron, donepezil, methylphenidate, iso-propyl myristate, i-methol, methyl salicylate, diphenhydramine, tolu- buterol, buprenorphine, clonidine, scopolamine, enzymes, such as bromelaine or vitamins, such as vitamins A, the group of B vitamins, C, D, E, K or combi nations or derivatives thereof
  • a polymer selected from the group consisting of a cyclic olefin copolymer (COC), a polyamide (PA), an ethylene vinyl alcohol (EVOH), a cyclic block copolymer (CBC), a polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), or a high density polyethylene (HDPE), a polypropylene (PP), a polyethylene terephthalate (PET) or an ethylene-meth- acrylic acid copolymer (EMAA) in a contact layer of a film for packaging an active ingredient in solid oral dosage form held in a container comprising the same polymer as the contact layer and where the film is induction welded to an opening of the container as well as methods for making the same.
  • COC cyclic olefin copolymer
  • PA polyamide
  • EVOH ethylene vinyl alcohol
  • CBC cyclic block copolymer
  • PVDF polyvinylidene fluoride
  • a method for preparing the packaged product comprising: a laminate film, a container; and an active ingredient wherein the packaged product is provided, by the steps of: i) providing a base layer, which is water and/or oxygen resistant and comprises a metal; ii) providing a contact layer; iii) coextrusion coating the base layer with a coextrusion layer, said coextrusion layer comprising the contact layer and a tie layer; and iv) allowing the coextrusion layer and the base layer to adhere to pro vide the laminate film; where the contact layer comprises a polymer selected from the group consisting of a cyclic olefin copolymer (COC), a polyamide (PA), an ethylene vinyl alcohol (EVOH), a cyclic block copolymer (CBC), a polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), a high density polyethylene (HDPE), polypropylene (PP), poly
  • Fig. 1A shows a schematic representation of a packaged product accord ing to the present invention
  • Fig. IB shows a schematic representation of a packaged product as shown in Fig. 1A in which the laminate film remains adhered to the container when the lid is removed from the container;
  • Fig. 1C shows a schematic representation of a packaged product as shown in Fig. 1A in which the laminate film is removed with the lid when the lid is removed from the container.
  • film contem plates at least a base layer to which a tie and a contact layer are co-extrusion coated to. Further outer layers may be added such as PET and paper.
  • a "packaged product” is in the context of the invention intended to mean an active ingredient in a container sealed with the films according to the invention and optionally a lid.
  • oxygen and water resistant contemplates material for which the oxygen transfer rate (OTR) and/or water vapor transfer rate (WVTR) is no more than 1, preferably no more than 0.1 as further detailed below.
  • OTR oxygen transfer rate
  • WVTR water vapor transfer rate
  • MVTR moisture vapor transfer rate
  • the term "mechanically wear resistant layer” as used to describe the outer layer should be understood as a material which is suitable for the man ufacture of a flexible packaging.
  • the mechanically wear resistant layer may be chosen from but are not limited to materials such as polyethylene or polyamide based sheets, ortho-phthalaldehyde based sheets, or polyester based sheets or combinations.
  • the mechanically wear resistant material i.e. the first outer layer, can be provided as a film that is biaxially oriented to give the packaging a higher mechanical strength, such as tear strength.
  • the term "bi axial oriented” should be understood such that the provided polymer film has been stretched in both a longitudinal and a transverse direction during manu facturing.
  • exterior side should be understood in its broadest sense.
  • the term exterior environment is used for defining the direction opposite of the side that is facing the composition or compound to be sealed by the laminate or packaging of the present invention. This means that the term exterior envi ronment is independent on whether additional layers are coated, laminated or otherwise attached to the film. Thus, the word is used for specifying in which direction a side of a layer is facing.
  • the base layer com prises a metal but may otherwise comprise a material selected from but not limited to a metal foil, preferably aluminium foil, a polymer selected from pol yamide, polyvinylidene chloride, silicon or aluminium oxide coated polyesters, and/or fluro polymers, such as commercial Alu foil from e.g. Hydro, or AIOx coated PET films obtainable from e.g. Toray Films Europe, or SiOx coated PET films obtainable from e.g. Celplast under the tradename Ceramis®.
  • a metal foil preferably aluminium foil
  • a polymer selected from pol yamide, polyvinylidene chloride, silicon or aluminium oxide coated polyesters and/or fluro polymers, such as commercial Alu foil from e.g. Hydro, or AIOx coated PET films obtainable from e.g. Toray Films Europe, or SiOx coated PET films obtainable from e.g. Celplast under the tradename Ceramis®.
  • water and/or oxygen resistance suitably encompasses materials having an oxygen transfer rate (OTR) equal to or below 1 cm 3 /rn 2 /24hr/bar according to ASTM standard D3985 at 23°C and 0% RH and/or water (or moisture) vapor transfer rate (WVTR) equal to or below 1 g/m 2 /24hr according to ASTM standard F1249 at 38°C and 90%RH, preferably both the WVTR and the OTR are below 0.01 g/m 2 /24hr or 0.01 cm 3 /m 2 /24hr/bar respectively.
  • OTR oxygen transfer rate
  • WVTR water (or moisture) vapor transfer rate
  • the base layer of the film is selected to provide a number of properties to a laminate film and packaging comprising the laminate film.
  • the base layer may give desired barrier and support prop erties to the final laminate/packaging.
  • the base layer may be a gas and water impermeable base layer, more preferably a water and/or oxygen resistant base layer.
  • the metal of the base layer is responsible for dis tributing the heat to the polymer layers during the induction welding. Aluminium is the most preferred base layer, aluminium is price com petitive, a superior barrier to all gases and moisture. Furthermore, similar to other metal-like materials, aluminium has good dead-fold properties, i.e. it does not unfold once folded, it reflects radiant heat, and gives a decorative appeal to laminates and packages.
  • the thickness of the base layer is 5 - 15 pm, preferably 7 - 12 pm, more preferred 8 - 10 pm, such as 9 pm, particularly when the base layer comprises or consists of aluminium.
  • the thickness may be higher, for example in the range of 1 - 50 pm.
  • the contact layer (or seal layer, the terms are used interchangeably) must be chemically resistant/inert to the active in gredient and excipients, to be packaged. Further, the contact layer must show a low absorption of the substances migrating through the film or laminate. The allowed degree of absorption for a given substance is typically dictated by the manufacturer of the substance but often the accepted values lie in the range of 0 to 1 % (w/w). For some products up to 10 % (w/w) is acceptable, typically for products with a low initial API content. The absorption is calculated as the weight of API in a packaging after storage at the set duration for a particular product relative to the initial weight of the API in the commercial product. A typical shelf life is around 2 years, such as 18 months to 5 years. Further, the contact layer must be sealable to the container.
  • the contact layer suitably comprises a polymer selected from the group consisting of a cyclic olefin copolymer (COC), a polyamide (PA), an eth ylene vinyl alcohol (EVOH), a cyclic block copolymer (CBC), a polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), a high density polyethylene (HDPE), a polypropylene (PP), a polyethylene terephthalate (PET) or an eth- ylene-methacrylic acid copolymer (EMAA).
  • the contact layer may comprise at least 30% (w/w) of the polymer.
  • the contact layer is a blend of one of the polymers as defined hereinabove in combination with a lower grade polymer such as polyethylene (PE), polyethylene blends, or other polymers known to the skilled person.
  • a lower grade polymer such as polyethylene (PE), polyethylene blends, or other polymers known to the skilled person.
  • the contact layer suitably or preferably comprises at least 30% (w/w) of COC, PA, EVOH, CBC, PVDF, COP, HDPE, PP, PET or EMAA.
  • the contact layer suitably or preferably com prises at least 50% (w/w) of COC, PA, EVOH, CBC, PVDF, COP, HDPE, PP, PET or EMAA.
  • the contact layer may be made of a material selected from cyclic olefin copolymer, a polyamide, an ethylene vinyl alcohol, a cyclic block copolymer, a polyvinylidene fluoride, a cyclic olefin polymer, a high density polyethylene, or an ethylene-methacrylic acid copolymer (EMAA) or mixtures thereof, such as the commercial products 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 obtainable from Nippon Gohsei under the tradename Soarnol®, COC films may be provided by Amcor or Plastique Venthenat.
  • EVAL® C109B sold by Kuraray
  • Selar PA 3426 R sold by Dupont® or COC 6013M-07
  • ViviOn 8210 sold by USI corporation (CBC), Kynar® 710 sold by Zeus Industrial Prod ucts (PVDF), ZEONOR® 1420R sold by Zeon Specialty Materials, Inc. (COP), CG9620 or CG8410 sold by Borealis AG (HDPE) and Surlyn® sold by Dupont®
  • Table 1 Examples of commercial products of polymers usable as contact layer according to the invention.
  • the contact layer consists of only one material, i.e. the con tact layer is a cyclic olefin copolymer (COC), a polyamide (PA), an ethylene vinyl alcohol (EVOH), a cyclic block copolymer (CBC), a polyvinylidene fluoride (PVDF), a cyclic olefin polymer (COP), a high density polyethylene (HDPE), a polypropylene (PP), a polyethylene terephthalate (PET) or an ethylene-met- hacrylic acid copolymer (EMAA).
  • the contact layer is a monolayer. Even more preferred the contact layer is a monolayer of one material. Despite the challenges with providing a single component contact layer this may be preferential to avoid scalping since blends including PE may become permeated and thus result in a sieve-like layer over time.
  • the contact layer comprises any of the polymers from the group above, even having a relatively low RED value, a chemical resistant film and laminate may be obtained even though the men tioned polymers chemically represent different polymer types.
  • Tests have shown that the resistance of laminates in which the laminate film comprises the preferred polymers show results similar to or better than those of laminates coated/laminated with e.g. the commercial product Barex®.
  • the RED value or the HSP parameter is a parameter known to the skilled person and more details can be found i.a. in Hansen, C., M., Hansen Solubility Parameters a User's Handbook 2 nd Ed., CRC Press, Boca Raton, 2007.
  • EVOH is normally used in laminates due to the superior oxygen barrier properties of EVOH and tear strength. Despite being known to be very hydro philic and hygroscopic (i.e. has a high WVTR) EVOH is very suitable as a contact layer according to the invention. Also, polyamide (PA) has typically been used in laminates due to the superior mechanical properties like tear strength or as a barrier. As for EVOH, it is noteworthy that PA may be used as a contact layer for providing a chemical resistant laminate film despite the hydrophilic nature of PA. Particularly preferred is a HDPE as contact layer. HDPE is used in many containers for solid oral dosage forms. Having realized the unexpected ad vantage of being able to use HDPE as a contact layer for active ingredients such as those detailed herein and moreover the unexpected ability to obtain good sealing when using induction welding this choice of polymer for use and for the packaged product is particularly preferred.
  • the container is made of LDPE.
  • the laminate film for use according to the invention may be tightly packed in a moisture barrier, in particular if it has to be stored.
  • the laminate film for use according to the invention may be packed immediately after man ufacture and should be kept safely packed until used in the inventive product.
  • the contact layer is made from a blend of at least two polymers.
  • blends can be a means for reducing the costs and for adapting the physical and chemical properties of the lamination process, such as reducing or increasing the melting temperature to comply with the profile of layers of a tie layer if present and the polarity of the blend to improve the adhesion properties of the layers and hence the robustness of the final product.
  • the cyclic olefin copolymer makes up at least 30% w/w of the blend of the contact layer, preferably at least 50% w/w, more preferably at least 60% w/w, more prefer ably at least 80% w/w, most preferably at least 95% w/w of the contact layer or each layer of the contact layer.
  • the contact layer is either a monolayer or comprised of two or more layers.
  • the tie layer may be selected from: ethylene methacrylic acid (EMAA), ethylene acrylic acid (EAA) preferably an ethylene acrylic acid having an acrylic acid content of minimum 10 % (W/W) based on the total weight of the ethylene acrylic acid layer (EEA-high acid), a terpolymer of ethylene, methacrylic acid and glycidyl methacrylate, terpolymer of ethylene, acrylic ester and maleic an hydride, preferably ethylene, butyl acrylate, and maleic anhydride (t-EBAMA), acrylic 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 poly ethylene (LDPE), a me tallocene compound, a polyethylene-copolymer or, a combination thereof.
  • EAA ethylene methacrylic
  • the laminates according to the invention further comprise a first outer layer, suitably made from a material selected from but not limited to paper, polyethylene or polyamide based sheets, ortho-phthalaldehyde based sheets, or polyester based sheets, or combinations, such as the commercial product F-PAP sold by Flexpet. It is preferred that the first outer layer is a combination of materials when polyester based sheets are used.
  • the laminate film further comprises a second outer layer fac ing the exterior side of the first outer layer.
  • the second outer layer is a paper layer.
  • the paper layer is typically printed with the name, color and/or logo of the product and manufacturer of the product. It is also or alternatively contemplated that the first outer layer can be printed.
  • the laminate film further comprises a second outer layer.
  • an adhesive and/or polymer agent may be ap plied between the base layer and the first and second outer layers.
  • the agent applied between these layers may be selected from the two-component adhe sive, extrusion laminated using a polymer selected from the group of materials used as tie layer according to the invention or a water based glue, the latter in particular when using a paper layer
  • suitable adhesives are adhesives approved for use in packag ing products for human use and are well known to the skilled person.
  • a suitable adhesive may be selected from but is not limited to polyurethane based adhe sives, epoxy based adhesives, or acryl based adhesives, well known to the skilled person.
  • the laminate film for use according to the present invention must be inert and impermeable to the compound which the laminate is in con tact with. Hence, in an embodiment of the invention a maximum of 10% (w/w), preferably a maximum of 5% (w/w), even more preferably a maximum of 1.5% (w/w), most preferably a maximum 0.5% (w/w) of the compound has migrated into the laminate film after 12 weeks of storage at 40 °C.
  • the container for use according to the invention typically has a lid and the laminate film is welded in between the opening of the container and the lid.
  • Such containers are well known.
  • the container is made of the same mate rial as the contact layer, and most often HDPE. It is however also contemplated that the container is made of a different material to which the contact layer can provide an airtight seal, when using induction welding.
  • air tight seal is to be understood as detailed below.
  • the container may be made of LDPE in the case of the contact layer being HDPE, LDPE and HDPE can without any further components upon induction welding provide an air tight seal.
  • Another variation is glass in such a situation the surface of the con tainer opening may be coated with an ethylene acrylic acid copolymer (EAA), such as EscorTM 5110 from ExxonMobil to which HDPE can provide an airtight seal.
  • EAA ethylene acrylic acid copolymer
  • an airtight seal means airtight at vac uum at 0.2 bar for at least 2 seconds.
  • One way of testing this is by sealing a laminate film to a container and allowing the sealed container to cool.
  • the container is placed in a desiccator tray with the bottom facing upwards where after the tray is closed. Vacuum is applied and if no bubbles are seen after a few seconds the sealing is considered to be airtight according to the invention.
  • a packaging should preferably comply with International standards such as 16 CFR ⁇ 1700.20 (for USA) and ISO 8317 (2003) corresponding to DIN EN ISO 8317 (2004) (for Europe).
  • a "packaging" is in the context of the invention intended to mean the packaged product.
  • the sealing of the packaged product is achieved in such a way that the contact layer of the laminate film is facing the opening of the container and the container is sealed using induction welding.
  • the active ingreistant held within the interior of the container will therefore in addition to the container itself only have direct contact with the contact layer of the laminate film.
  • Induction welding is a technology well known in the art.
  • FIG. 1A A schematic representation of a packaged product according to the present invention is shown in Fig. 1A.
  • the packaged product (2) comprises a container (4) inside of which there is active ingredient (6).
  • the active ingredient (6) is in the form of tablets.
  • a lid (10) At the top of the container (4) there is a lid (10).
  • the lid (10) is arranged to screw onto the container (4), although other known means of attachment can be used.
  • Fig. IB shows one form of the packaged product (2) of Fig. 1A when the lid (10) is opened.
  • the laminate film (8) re mains adhered to the container (4).
  • removal of the lid (10) does not break the seal between laminate film (8) and the container (4).
  • the laminate film (8) may be provided with a lip, protrusion or the like (not shown) to aid removal of the laminate film from the container.
  • Fig. 1C shows an alternative form of the packaged product (2) of Fig. 1A when the lid (10) is opened.
  • the laminate film (8) is removed inside of the lid when the lid (10) is removed from the container (4).
  • removal of the lid (10) breaks the seal between laminate film (8) and the container (4), with the laminate film (8) being re moved with the lid (10).
  • Tests were conducted to determine the RED and CHI values for PVDF, HDPE and EMAA samples for a range of chemical species.
  • HSP values and interaction radius require that the solubility of the drug is evaluated against at least 16 solvents having a range of polar and hydrogen bonding properties.
  • the methodology of determining HSP values, interaction radius and RED values is described in C.M. Hansen: "Hansen Solubility Parameters, A User's Handbook", CRC Press, 2007, Second Edition and exemplified in EP 2 895 531.
  • test tubes were then placed on a rolling bench for 24 hours and visually checked to see whether or not the samples had dissolved/swollen.
  • Table 2 5D, dR, dH, R, Fit values for PVDF, HD PE and EMAA samples
  • Table 3 RED and CHI values for HDPE, PVDF and EMAA
  • RED values reflect an experimental determi nation of R
  • CHI represents a theoretical determination based on the volume of the API.
  • APIs for which both the RED and CHI are around and above 1 are be- lieved to be very suitable for being packaged in a film faced by the contact layer APIs where one of the RED and CHI (typically the CHI value) are below 1 are believed to be less suitable. APIs where both the RED and CHI are below 1 are believed to be even less suitable for being packaged in films having the subject contact layer.
  • the contact layers tested have a broad applicability as contact layer for APIs (values under 1 are in italics).
  • Example 2 Strength of Coextrusion examples using HDPE as an example of contact layer:
  • Tie layer 2 Nucrel® 0609HSA (an ethylene methacrylic acid)
  • Tie layer 1 PE MI15 (a PE, e.g. Borealis® CA9150)
  • Contact layer Borealis® CG9620 (an HDPE)
  • Puncture resistance - according to ASTM F1306 with the following modifica tions: sample diameter 48mm instead of 34.9mm and puncture tool tip diam eter 3.0 mm instead of 3.2 mm).
  • the sealing strength test was made under the following conditions: 160°C, 500N pressure, 0.5 seconds.
  • the exploration strength test was made as follows: a four-sided sealed bag was sealed with parameters 160°C, 0.5 seconds and 500 N pressure, with a size of 80mmx90mm including a 5mm wide sealing area. The bag was held and penetrated with a syringe connected to a pressure de vice. The bag was then inflated to a pressure of 0.2 bar in one test (Exploration test 1) and 0.25 bar in another test (Exploration test 2). The success criteria for a given laminate is to withhold the pressure for 30 seconds without burst ing.
  • 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 layers or total thickness of the coextrusion layer.
  • samples 1 to 9 show puncture re sistance from 36.7N to 46.4N (front side). This is only an increase of approxi mately 22 percent even though the coating weight increases as much as 4 times from the lowest loading to the highest. This indicates that the main in fluence on puncture resistances is the base material.
  • Sample 1 has a contact layer loading of 7.4 g/m 2 which is almost the same as sample 2, but sample 2 has a significantly higher seal strength.
  • Sam ple 5 has a contact layer loading of 14 g/m 2 but has a sealing strength lower than sample 4 which has a contact layer loading of 12 g/m 2 . It is noted that the measured total loading of sample 5 was 17 g/m 2 , even though the target of the layer distribution was 20 g/m 2 , which indicates that the loading of the tie layers is, in reality, lower than 3 g/m 2 which may explain the difference.
  • Example 3 Induction welding tests with HDPE, PP and COC contact layers
  • Lak/AL29/ CoexHDPE35 (Primacor 4608 5g / PE MI15 CA9150 5g / HDPE CG9620 25g)
  • the product used for the contact layer, WG341C, contains 30% PE and 70% PP.
  • PET36/AL9/CoexCOC30 Litader 3410 17, 5g / COC 8007F-600 12, 5g
  • the samples all use aluminium base layers.
  • Lak refers to a lacquer on the outer part of the film. This is intended to protect the aluminium layer from corrosion and is understood not to have any impact on sealing performance.
  • the lacquer used was Flint Group PreCoat FMET Overprint Varnish - WP5200CF.
  • the film-container combinations were subjected to induction welding. Some of the tests were conducted with a relatively low current provided during the induction welding; these results are represented under the "low” portion of Table 8. The tests were repeated with a relatively high current provided during the induction welding; these results are represented under the "high” portion of Table 8.
  • the low current is representative of the lower end of the spec trum of current used commercially and the high current is representative of the higher end of the spectrum of current used commercially in induction weld ing applications similar to that of the present invention.
  • the films with HDPE contact layer give an acceptable seal with the HDPE container, under both the “high” and “low” current regimes.
  • the films with the PP contact layer also give an acceptable seal with the PP container under both the “high” and “low” current regimes.

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Abstract

La présente invention concerne des récipients scellés avec des films stratifiés, dans lesquels une couche de coextrusion comprend une couche de contact et au moins une couche de liaison collée à une couche de base, par soudage par induction et contenant des ingrédients actifs, la couche de contact étant à base de COC, PA, EVOH, CBC, PVDF, COP, HDPE ou EMAA et le récipient étant constitué du même matériau.
PCT/EP2022/050288 2021-01-08 2022-01-07 Films stratifiés destinés à être utilisés dans des récipients pour formes posologiques orales solides, ainsi que leur utilisation et leur préparation WO2022148848A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012093036A1 (fr) * 2011-01-05 2012-07-12 Tetra Laval Holdings & Finance S.A. Matériau d'emballage stratifié sans feuil d'aluminium, procédé de fabrication du matériau d'emballage stratifié et récipient d'emballage produit avec ce matériau
EP2895531A1 (fr) 2012-09-14 2015-07-22 Dow Global Technologies LLC Composition contenant un copolymère éthylène/alpha-oléfine à faible viscosité ou un copolymère éthylène/alpha-oléfine fonctionnalisé à faible viscosité
WO2015123211A1 (fr) 2014-02-11 2015-08-20 Bemis Company, Inc. Film d'emballage pharmaceutique anti-revente
WO2017100182A1 (fr) * 2015-12-07 2017-06-15 Bemis Company, Inc. Films piégeant l'oxygène, emballages et procédés associés
WO2017114922A1 (fr) 2015-12-29 2017-07-06 Danapak Flexibles A/S Procédé permettant d'obtenir un film résistant aux produits chimiques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012093036A1 (fr) * 2011-01-05 2012-07-12 Tetra Laval Holdings & Finance S.A. Matériau d'emballage stratifié sans feuil d'aluminium, procédé de fabrication du matériau d'emballage stratifié et récipient d'emballage produit avec ce matériau
EP2895531A1 (fr) 2012-09-14 2015-07-22 Dow Global Technologies LLC Composition contenant un copolymère éthylène/alpha-oléfine à faible viscosité ou un copolymère éthylène/alpha-oléfine fonctionnalisé à faible viscosité
WO2015123211A1 (fr) 2014-02-11 2015-08-20 Bemis Company, Inc. Film d'emballage pharmaceutique anti-revente
WO2017100182A1 (fr) * 2015-12-07 2017-06-15 Bemis Company, Inc. Films piégeant l'oxygène, emballages et procédés associés
WO2017114922A1 (fr) 2015-12-29 2017-07-06 Danapak Flexibles A/S Procédé permettant d'obtenir un film résistant aux produits chimiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HANSEN, C.M., HANSEN: "Hansen Solubility Parameters, A User's Handbook", 2007, CRC PRESS

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