DE202018006230U1 - Improved films and laminates for use in the packaging of reactive compounds - Google Patents

Abstract

A laminate film comprising at least one base layer, which is water and / or oxygen resistant, and a coextrusion layer containing a tie layer and a contact layer, wherein the contact layer is a polymer selected from the group consisting of a cycloolefin copolymer, a polyamide, or an ethylene Vinyl alcohol, wherein the total loading of the tie layer is in the range of 3 to 9 g / m and wherein the loading of the contact layer is loading = x * loading, where x is in the range of 1 to 3, particularly preferably 1.33 to 2.75, wherein the contact layer is the innermost layer and is adapted to face a composition that is packaged in the film.

Description

The present invention relates to improved laminates having a base layer, such as a metal foil, wherein a tie layer and a contact layer are coextruded, and uses of the sheeting and laminates to package APIs (drugs) such as nicotine, fentanyl, lidocaine, and rivastigmine. wherein a particular ratio of bond to contact layer provides good mechanical properties and improved sealing properties.

Background of the invention

In the pharmaceutical industry, substances, including very aggressive substances such as nicotine, fentanyl, rivastigmine and lidocaine, are packaged as tablets in inhalers, patches, etc., resulting in particular packaging, laminate or foil requirements for sealing these substances to ensure that no adverse decomposition or absorption takes place.

• - mechanisch stabiles Laminat, das sich nicht auftrennt oder verformt
• - Sicherstellen, dass die Verpackung kindersicher ist, um die Sicherheit von potenziell gefährlichen Verbindungen zu erhöhen
• - Inerte Eigenschaften, die sicherstellen, dass chemische Verbindungen nicht von der äußeren Umgebung eines Laminats durch das Laminat migrieren und in Kontakt mit der versiegelten Substanz kommen, und
• - dass der eingeschlossene API nicht mit der Oberfläche, mit der er in Kontakt ist, reagiert oder durch sie migriert.

A common example is the problem of packaging nicotine, especially as a nicotine patch, because nicotine is very aggressive towards its environment and highly volatile. These properties are problematic for consumer safety and product shelf life if they are not addressed, because it is important that the amount of nicotine in eg a tablet, a chewing gum or a patch is stable and meets the product specification. It is also important to avoid adverse reactions between the packaging and the pharmaceutical substance. In addition, a long, stable shelf life is very desirable from an entrepreneurial point of view. Thus, chemical requirements for a package, film, or laminate are typically:

• - mechanically stable laminate that does not separate or deform
• - Make sure that the packaging is childproof to increase the safety of potentially dangerous connections
• Inert properties that ensure that chemical compounds do not migrate from the outer environment of a laminate through the laminate and come into contact with the sealed substance, and
• - The included API does not react with or migrate through the interface it is in contact with.

One known polymer meeting the requirements of extreme chemical resistance and inert properties is a polyacrylonitrile (PAN) -based film sold, for example, under the trade name Barex® as resins, which i.a. produced by the company Ineos. Barex® is widely used and approved for drug and food applications and is used 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, and / or drugs such as nicotine.

Furthermore, extruded Barex® resin is heat stable and therefore weldable at temperatures around 160 to 220 ° C, making it suitable for use in flexible packaging. However, Barex® is being sold at a high price because of difficulties in its production and subsequent extrusion into a film that results in high material loss. In addition, Barex®'s water and oxygen resistance is not satisfactory for all purposes.

Another solution is in the WO 00/44559 which discloses a material for packaging nicotine-containing products (eg, patches, tablets, lozenges, nasal spray), the material comprising a polymer based on dimethyl 2,6-naphthalenedicarboxylate and / or 2,6-naphthalene dicarboxylic acid monomers , It is also disclosed that a polymeric film is combined with other barrier materials to form a laminate to further enhance the barrier properties of the laminate. The preferred material for a laminate is aluminum because of its good oxygen and water barrier properties.

Another solution is in the WO 2017/114922 of the present applicant, which discloses a film having a coextrusion layer comprising a tie layer and a contact layer, wherein the contact layer is the innermost layer facing an aggressive chemical drug, such as rivastigmine, nicotine, fentanyl or lidocaine. The contact layer may include polyamide, cycloolefin copolymer or ethylene vinyl alcohol. The connection layer is on a Base layer co-extrusion coated so that the tie layer is in contact with the base layer and the contact layer.

Another solution is in the WO 2015/123211 which discloses a film having a tie layer and a contact layer containing COC and facing a drug such as nicotine. The film may be made by providing a coextrusion layer comprising a tie layer and a contact layer and coating it on aluminum foil.

Therefore, in view of the increased market and demand for packaging, there is an immediate need to find various solutions to produce stable laminates in a cost efficient manner.

Summary of the invention

Against this background, it is an object of the present invention to provide solutions that meet one or more of the requirements described above, that is, i.a. Solutions that impart impermeability and inertness to packaging while still providing a mechanically strong laminate that does not separate or deform, does not puncture, but is sealable and otherwise resistant to mechanical impact.

Accordingly, in a first aspect, this is achieved by providing a laminate film which comprises at least one base layer, which is resistant to water and / or oxygen, and a coextrusion layer, which contains a bonding layer and a contact layer, wherein the contact layer selects a polymer from the group consisting of a cycloolefin copolymer, a polyamide, or an ethylene-vinyl alcohol, and
wherein the total loading of the tie layer is in the range of 3 to 12 g / m ² and wherein the loading of the contact layer loading _contact = x * loading is _compound , where x is in the range of 1 to 3, particularly preferably 1.33 to 2.75, lies,
wherein the contact layer is the innermost layer and is adapted to face a composition packaged in the film.

It has been found that when the tie layer and the contact layer are coextruded according to the invention, the loading of the tie layer is of unimportant importance for good processability of the finished film and laminates or packages made from the film.

The loading of the coextrusion layers according to the invention also surprisingly led to a better adhesion of the various layers after coextrusion, resulting in a homogeneous film in which the individual layers do not separate from one another.

It has also been found that in addition to better fabrication, the chemical resistance of the film is also improved by reducing the loading of the tie layer relative to the contact layer.

While it has previously been assumed that the tie layer does not contribute significantly to the chemical resistance of the film, but only to the stability of the laminate, the present inventors have surprisingly found that by providing a relatively low loading tie layer and a contact layer that is about the same or better higher loading, preferably higher loading than the tie layer, improved reaction inertness and / or API uptake such as nicotine, rivastigmine, fentanyl and lidocaine was obtained. At the same time, laminates with better or at least as good mechanical properties as prior art products have been provided.

Thus, in contrast to what has been previously thought, a smaller bond layer combined with a same or larger contact layer confers better overall properties to the finished laminate or film.

In a preferred embodiment, the tie layer is multi-layered. When the bonding layer is a multi-layer, a first bonding layer is the layer adjacent to the contact layer. The numbering of the layers of the multilayer connecting layer thus increases, depending closer to the base layer. For example, if the multilayer interconnect layer consists of two layers, the film has the following structure:
Base layer / second tie layer / first tie layer / contact layer (the last three being coextruded).

In the present invention, a polymer of interest for use as a tie layer or contact layer may be selected by calculating the RED value, which is generally used, the solubility of a polymer in a particular solvent, or the compatibility of two polymers in a mixture predict. Accordingly, the RED values have been calculated for various polymer / solvent systems wherein the polymer is the polymer that forms the contact layer or is a polymer for use as a tie layer, and the solvent is an aggressive chemical such as nicotine, rivastigmine, Fentanyl and lidocaine etc., is.

The RED value for the polymer and the aggressive chemical is calculated using the Hansen Solubility Parameter (HSP) theory described in CM Hansen: Hansen Solubility Parameters, A User's Handbook, CRC Press, Boca Raton, 1999 is.

• - δ_D für Dispersions-Kohäsionsenergie
• - δ_P für dipolare Kohäsionsenergie
• - δ_H für Wasserstoffbrückenbindungs-Kohäsionsenergie

The HSP system between the polymer and the aggressive chemical substance is described by parameters arranged in a three-dimensional coordinate system:

• - δ _D for dispersion cohesive energy
• - δ _P for dipolar cohesive energy
• - δ _H for hydrogen bond cohesion energy

The HSP distance Ra between polymer and aggressive chemical substance is given by: $${\text{<figure-callout id="2" label="Ra" filenames="DE202018006230U1\_0003.png" state="{{state}}">Ra</figure-callout>}}^2=4{\left(\mathrm{\Delta }{\mathrm{\delta }}_{\text{D}}\right)}^2+\mathrm{<figure-callout\; id="2"\; label="\Delta \; \delta \; P"\; filenames="DE202018006230U1\_0003.png"\; state="\{\{state\}\}">\Delta \; </figure-callout>}{\mathrm{\delta }}_{\text{P}}{}_{}{}^2+\mathrm{<figure-callout\; id="2"\; label="\Delta \; \delta \; H"\; filenames="DE202018006230U1\_0003.png"\; state="\{\{state\}\}">\Delta \; </figure-callout>}{\mathrm{\delta }}_{\text{H}}{}_{}{}^2$$

The Δ indicates the difference between the aggressive substance and the polymer for the given parameter.

wobei Ro der Interaktionsradius ist, der den Radius der Sphäre im Hansen-Raum bestimmt, und das Zentrum die drei Hansen-Parameter sind. Alle Werte werden mit empirischen Daten berechnet oder bestimmt und es ist dem Fachmann bekannt, wie die Werte berechnet werden.The relationship between the HSP distance, Ra and RED is given by: $$\text{RED}=\text{Ra / Ro}.$$

where Ro is the radius of interaction that determines the radius of the sphere in Hansen space, and the center is the three Hansen parameters. All values are calculated or determined using empirical data and it is known to those skilled in the art how the values are calculated.

• RED < 1, das Polymer und die aggressive chemische Substanz werden sich lösen,
• RED = 1, das Polymer und die aggressive chemische Substanz werden sich teilweise lösen,
• RED > 1, das Polymer und die aggressive chemische Substanz werden sich nicht lösen

The obtained RED value indicates whether or not the polymer is likely to dissolve in the aggressive chemical substance:

• RED <1, the polymer and the aggressive chemical will dissolve,
• RED = 1, the polymer and the aggressive chemical will partially dissolve,
• RED> 1, the polymer and the aggressive chemical will not dissolve

The resulting RED value is used to give an indication of the probability of solving or not solving.

All values can be calculated using the Hansen Solubility Parameter in Practice (HSPiP) software, which is commercially available at http://hansen-solubility.com.

According to the invention, the bonding layer is selected to provide sufficient adhesion between the base layer and the co-extrusion layer, but also provides chemical resistance. The tie layer can impart melt strength and aid coextrusion coating of both the multilayer tie layer and the contact layer.

It is preferred that the melt profile of the polymers forming the tie layer and the polymer or polymers that form the contact layer are in the same range to provide optimum films that do not separate. Preferably, all layers contain polymers which melt at the operating temperature of the process of the present invention, and even more preferably, the melting profiles (ie, melting points) of the respective polymers should be less than 30 ° C, preferably 0 to 15 ° C such as 5 to 15 ° C, differ.

In one embodiment, the tie layer is a multiple layer made, for example, of 2, 3, 4, or 5 layers. In this way, the properties of the film and the resulting laminates and packages can be improved with regard to the quality of the finished laminate film, but also to adapt the specific chemical and physical properties of the contact layer and / or the base layer. Preferably, the bonding layer consists of two layers.

In one embodiment, at least one layer of a multilayer tie layer is selected from ethylene-methacrylic acid (EMAA), ethylene-acrylic acid (EAA), a terpolymer of ethylene, methacrylic acid and glycidyl methacrylate, terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene, butyl acrylate and maleic anhydride ( t-EBAMA) or a combination thereof.

In the same or another embodiment, another or the second layer of the multilayer tie layer is selected from a terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene-butyl acrylate, maleic anhydride (t-EBAMA), ethylene-methacrylic acid (EMAA), ethylene-methyl acrylate (EMA), ethylene-butyl acrylate (EBA), ethylene-ethyl acrylate (EEA), ethylene-acrylic acid (EAA), preferably an ethylene-acrylic acid having an acrylic acid content of at least 10 wt .-% relative to the total weight of the ethylene-acrylic acid layer ( EEA acid range), or low density polyethylene (LDPE) or a combination thereof.

The RED values of the monomers present in t-EBAMA and EAA were calculated to illustrate the aggressive chemicals nicotine, rivastigmine, lidocaine, and fentanyl. The results are shown in Table 1 below. Table 1: RED values for polymers which are used according to the invention in the tie layer polymer monomer lidocaine rivastigmine nicotine fentanyl t-EBAMA butyl acrylate 0.63 0.71 0.53 1.22 t-EBAMA maleic anhydride 1, 61 1.59 1, 90 4.24 EEA methacrylic acid 1.89 1.41 1.31 3.55 polyethylene 1.65 1, 66 0.55 1.12

Each layer of the film or laminate of the present invention may be determined by a material, such as polymer (s), and its loadings. If necessary, the skilled person will be able to calculate from the loading and the density of the material used also the thickness of each layer. Most polymers that can be used in connection with the present invention have a density of about 1 g / cm ^3, such as 0.90 g / cm ³ to 1.10 g / cm ^3, on.

In Table 2, non-limiting examples of commercially available polymers with their respective densities are listed which can be used as a first or second layer of the multilayer interconnect layer or as a contact layer. Table 2: Examples of commercial polymer products that can be used in the invention. Surname Used abbreviation trade name Density (g / cm ³ ₎ Cycloolefin copolymer COC Topas ^® 8007F-600 1.01 (according to ISO 1183) Cycloolefin copolymer COC Topas ^® 9506F-500 1.01 (according to ISO 1183) Cycloolefin copolymer COC Topas ^® 7010F-600 1.02 (according to ISO 1183) polyamide PA Selar ^® PA 3426R 1.19 (according to ISO 1183) Ethylene-methacrylic acid EMAA Nucrel ^® 0609 0.93 (according to ASTM D792) Terpolymer of ethylene, butyl acrylate, maleic anhydride t-EBAMA Lotader ^® 3410 0.94 (according to ASTM D1505) Terpolymer of ethylene, butyl acrylate, maleic anhydride t-EBAMA Lotader ^® 3210 0.94 (according to ISO 1183) Ethylene-acrylic acid EAA Escor ™ 6000 0.932 (according to ASTM D1505) Ethylene-acrylic acid EAA acid rich Escor ™ 5110 0.939 (according to ASTM D1505)

In another embodiment, the layers, such as the first layer and the second layer of the multilayer interconnect layer, comprise different polymers.

Through various polymers forming the first and second tie layers, the laminate film can be optimized to have both improved mechanical properties of the film.

According to the invention, it has been found that the ratio of the loading (g / m ² ) of the respective bonding layers has an effect on the mechanical properties of the film.

Accordingly, in one embodiment of the invention wherein the tie layer comprises two layers, the ratio of the load (g / m ² ) of the at least two layers is approximately 1: 1.

In a particular embodiment, in which the bonding layer consists of two layers with a loading of 1: 1, the loading of the contact layer is
Loading _contact = x * loading _compound , where x is in the range of 1.33 to 2.75.

The inventors have found that a film having unexpectedly improved mechanical properties is obtained when the loading of the two layers of the multilayer interconnect layers is approximately equal. At the same time, the total load could be reduced, such as 4 to 8 or 4 to 6 g / m ² , thereby saving material and reducing production costs.

In another embodiment, all layers of the multilayer tie layer are coextruded with the contact layer to facilitate processing and to ensure homogeneity of the layers.

The base layer, which is water and / or oxygen resistant, is selected from the group consisting of a metal foil, preferably aluminum foil, a polymer, such as a polymer made from polyamide, polyvinylidene chloride, silicon or alumina coated polyesters, and / or fluoropolymers.

According to the invention, water and / or oxygen resistance preferably comprises materials having an oxygen transfer rate (OTR) equal to or below 1 cm ³ / m ² / 24h / bar according to ASTM D3985 at 23 ° C and 0% RH and / or a water (or water) Moisture vapor transfer rate (WVTR) equal to or less than 1 g / m ² / 24h according to ASTM Standard F1249 at 38 ° C and 90% RH, preferably both WVTR and OTR are below 0.01 g / m ² / 24h or 0.01 cm ³ / m ² / 24h / bar.

According to the invention, the base layer of the film is selected to impart a number of properties to a laminate film and a package comprising the laminate film. The base layer can impart desired barrier and carrier properties to the final laminate or finished package. In addition, in one embodiment, the base layer may be a gas and water impermeable base layer, more preferably a water and / or oxygen resistant base layer.

In embodiments in which the contact layer is hygroscopic, the base layer is preferably made of a metal foil such as an aluminum foil.

Aluminum is competitively priced, an exceptional barrier to all gases and moisture. In addition, aluminum, like other metal-like materials, has good dead-fold properties, i. it does not unfold once folded, it reflects radiant heat and gives laminates and packaging a decorative effect.

According to the invention, the contact layer must be chemically resistant / inert to the final API to be packed, such as a so-called aggressive chemical substance, and, if present, an adjuvant.

In addition, the contact layer must show little absorption of the substances that migrate through the film or laminate. The permissible degree of absorption for a particular substance is typically dictated by the manufacturer of the substance, but often the accepted values are in the range of 0 to 1% by weight. For some products, up to 10% by weight is acceptable, typically for products with a low starting API content. Absorbance is calculated as the weight of the API in the package based on the initial weight of the API in the commercial product.

According to the invention, it has been found that, in contrast to previous assumptions, the contact layer should have the same or a greater charge than the connection layer. This provides a laminate that exhibits low absorption but at the same time has improved mechanical properties and is more cost effective to produce because of lower overall loading.

Without wishing to be bound by theory, it is believed that unlike previous theories, the contact layer will always take up a certain amount of substance to reach equilibrium. It has surprisingly been found that through a contact layer having a higher general loading and having a loading equal to or higher than the loading of the tie layer, the API, which is a very aggressive compound, only in the contact layer and not absorbs the bonding layer.

It is believed that if the tie layer has a higher loading and the contact layer has less loading within certain areas, as previously applied with the intention of ensuring proper lamination and sealing, the tie layer will act like a sponge, which absorbs the compound through the contact layer and therefore the receiving balance with the contact layer is never reached and therefore the API is continuously absorbed by the contact layer in the bonding layer. The present invention solves this problem.

The contact layer contains a polymer selected from the group consisting of a cycloolefin copolymer (COC), a polyamide (PA) or an ethylene-vinyl alcohol (EVOH).

In another embodiment, a layer of the multilayer tie layer and contact layer includes a polymer selected from the same group of a cycloolefin copolymer (COC), a polyamide (PA), or an ethylene vinyl alcohol (EVOH). The layers may be the same or different material selected from the above.

The HSP and RED values calculated as mentioned above using http://hansen-solubility.com gave the following values for the preferred polymers of the invention using lidocaine / rivastigmine as a solvent (API): Table 3: HSP and RED values for preferred polymers according to the invention polymer D P H RED-value lidocaine 18.1 8.2 6, 1 - PA 66 16 11 24 1.72 COC 18 3 2 1.32 EVOH 20.5 10.5 12.3 1.12

It has been found that when the contact layer contains a polymer of the above relatively low RED group (i.e., between 1 and 2), a chemically resistant film and a laminate can be obtained although the polymers mentioned are chemically different types of polymer. Tests have shown that the durability of laminates in which the film is coated with the preferred polymers shows results which are surprisingly similar to those of laminates e.g. coated / laminated with the commercial product Barex® are superior.

EVOH is normally used because of the extraordinary oxygen barrier properties of EVOH in laminates. Although EVOH is known to be very hydrophilic and hygroscopic (i.e., high in WVTR), it is very useful in the present invention.

In addition, polyamide (PA) has typically been used because of exceptional mechanical properties such as tear strength or as a barrier in laminates. As for EVOH, it is noteworthy that, despite the hydrophilic nature of PA, PA can be used as a contact layer and / or coextrusion layer (i.e., bonding and contact layer) to provide a chemically resistant laminate film.

In a preferred embodiment, in which the contact layer is a polyamide, the loading of the contact layer is 3 to 27 g / m ² , preferably 6 to 10 g / m ² , particularly preferably 8 g / m ² . As a result, the bonding layer or the plurality of bonding layers may be 3 to 9 g / m ² and in the more preferred embodiment 3 to 8 g / m ² .

In a preferred embodiment, because of the hydrophilic nature of PA and EVOH, the laminate film obtained according to the present invention may be tightly packaged in a moisture barrier, especially when stored. The laminate film of the present invention may be packaged immediately after production and should remain until further use, e.g. stored in a packaging line, safely packed.

COC has not previously been found to be very suitable for coextrusion coatings and for the production of heat sealable laminates. Without wishing to be bound by theory, it is believed that this is due to the stress experienced by the polymer in an extrusion process. The stress causes irregular heating and melting within the COC, resulting in the finished film or laminate being unacceptable from an optical point of view in various packaging industries. Therefore, it was surprising that the inventors succeeded in providing a coextrusion layer comprising COC as a contact layer for sealing aggressive substances.

In another variation, the polymer or polymers of the tie layer have a melting point that differs from COC by 30 ° C or less, preferably 0 to 15 ° C, such as 5 to 15 ° C.

In a preferred embodiment, in which the contact layer is COC, the loading of the contact layer is 3 to 27 g / m ² , preferably 12 to 24 g / m ² , particularly preferably 17 to 24 g / m ² . Accordingly, the bonding layer or the plurality of bonding layers may be 3 to 9 g / m ² and in the more preferred embodiment 3 to 8 g / m ² .

As a result of having been able to process a chemically resistant laminate having a coextruded layer laminated to a base layer, thin laminates can be obtained and, generally, improved processability is achieved during the manufacture of the laminates or packages.

Accordingly, in one embodiment, the multilayer tie layer has a total loading in the range of 3 to 9 g / m ² and / or the contact layer has a loading in the range of 3 to 27 g / m ² and the loading of the laminate is not more than 40 g / m ² , more preferably at most 35 g / m ² .

In the context of the present invention, "loading" means the weight of the polymer used per m ² . The exact total weight of the finished laminate may vary slightly due to the loading of the various individual layers.

In a specific embodiment, the contact layer of the coextrusion layer is made of a mixture of at least two polymers. The use of mixtures may be a means to reduce costs and to adjust the physical and chemical properties of the coextrusion process, such as reducing or increasing the melting temperature to match the profile of layers of the tie layer, and the polarity of the mixture In order to improve the adhesion properties of the layers and thus the resistance of the finished product.

In a preferred embodiment, the contact layer is of a polymer type.

In one embodiment, at least one or all of the polymer or polymers that form the contact layer of the coextrusion layer is a cycloolefin copolymer, a polyamide or an ethylene-vinyl alcohol. Each of the polymers is commercially available, for example, 35 mole% ethylene-vinyl alcohol copolymer sold under the tradenames EVAL® C109B by Kuraray, an amorphous nylon (polyamide) resin sold under the trade name Selar PA 3426 R by Dupont Cycloolefin copolymer, Topas® 6013M07 marketed by Topas®. Other variations of the same functionalities are within the scope of the invention.

In a variation, the cycloolefin copolymer, a polyamide or an ethylene-vinyl alcohol constitutes at least 50% by weight of the mixture of the contact layer, preferably at least 60%, more preferably at least 80%, most preferably at least 95% % By weight of the contact layer.

According to the invention, a film according to the invention has various applications. In one embodiment of the invention, the film is used to package a composition containing a compound selected from nicotine, fentanyl, lidocaine and rivastigmine, which compound is preferably formulated as a patch, such as a transdermal patch.

When the composition is a plaster, according to the invention, the amount of the compound remaining at 40 ° C after storage for at least 7 days is at most ± 10% by weight compared to the same compound as index 100 in a similar one Barex® patch is sealed.

In another embodiment, the laminate film is heat sealable. A heat-sealable laminate film can be sealed during heat sealing without producing deformation of films or laminates. Deformation is undesirable in terms of quality assurance, where any deformation must be noted and explained, which is very labor intensive. In addition, legislation is very strict in many countries. Therefore, films and / or laminates with a deformation for the packaging of active ingredients are not allowed. Therefore, the mechanical properties are very important from a production cost efficiency point of view. It is also important that the laminates are firmly connected.

• i) eine Basisschicht, die wasser- und sauerstoffbeständig ist, bereitgestellt wird,
• ii) eine Schicht, die eine Verbindungsschicht und eine Kontaktschicht umfasst, coextrudiert wird, um eine Coextrusionsschicht bereitzustellen,
• iii) die Coextrusionsschicht auf die Basisschicht beschichtet wird,
• iv) die Coextrusionsschicht, die auf die Basisschicht beschichtet ist, härten kann, um die Laminatfolie bereitzustellen, die die mehrschichtige Verbindungsschicht und die Kontaktschicht umfasst, welche als eine auf die Basisschicht beschichtete Coextrusionsschicht gebildet sind,

wobei die Kontaktschicht ein Polymer ausgewählt aus der Gruppe bestehend aus einem Cycloolefin-Copolymer, einem Polyamid oder einem Ethylen-Vinylalkohol umfasst, und
wobei die Gesamtbeladung der Verbindungsschicht im Bereich von 3 bis 9 g/m² liegt und wobei die Beladung der Kontaktschicht Beladung_Kontakt = x*Beladung_Verbindung beträgt,
wobei x im Bereich von 1 bis 3, besonders bevorzugt 1,33 bis 2,75, liegt.A process is also a process for providing a laminate film according to the invention, in which

• i) a base layer which is water and oxygen resistant is provided,
• ii) a layer comprising a tie layer and a contact layer is coextruded to provide a coextrusion layer,
• iii) the coextrusion layer is coated on the base layer,
• iv) curing the coextrusion layer coated on the base layer to provide the laminate film comprising the multilayer interconnect layer and the contact layer formed as a coextrusion layer coated on the base layer,

wherein the contact layer comprises a polymer selected from the group consisting of a cycloolefin copolymer, a polyamide or an ethylene-vinyl alcohol, and
wherein the total loading of the tie layer is in the range of 3 to 9 g / m ² and wherein the loading of the contact layer loading _contact = x * loading is _compound ,
where x is in the range of 1 to 3, particularly preferably 1.33 to 2.75.

In other variations, the tie layer is a multiple layer, preferably comprising at least two layers, and all tie layers are coextruded with the contact layer.

In yet another embodiment, a first layer of a multilayer tie layer is at most 5 g / m ² .

It has been found that the loading of the first tie layer facing the contact layer is of particular importance for the properties of the finished laminate in terms of both adhesion, deformation and durability.

In one embodiment of the method, the contact layer has a loading in the range of 3 to 27 g / m ² , preferably 8 to 22 g / m ² .

In a further embodiment, the total loading of the bonding layer and the contact layer is not more than 40 g / m ² , preferably between 6 and 40 g / m ² , particularly preferably not more than 35 g / m ² .

In one embodiment, the curing of step iv) is instantaneous, for example, by cooling the coextrudate in cooling cylinders during the lamination process.

In one embodiment, the base layer, which is water and / or oxygen resistant, is selected from the group consisting of metal foil, preferably aluminum foil, polymers, polyamide, polyvinylidene chloride, silica coated polyesters, and / or fluoropolymers.

The contact layer is a polymer selected from the group consisting of a cycloolefin copolymer, a polyamide or an ethylene-vinyl alcohol.

In yet another embodiment, the multilayer tie layer has two layers and the two layers are the same polymer.

• - eine erste Außenschicht, die aus einem verschleißfesten Material hergestellt ist,
• - eine erfindungsgemäße Laminatfolie, wobei die Seite der Basisschicht der Laminatfolie der ersten Außenschicht zugewandt ist, umfasst.

In addition, a package is provided for packaging a composition containing a compound, wherein the laminate is at least

• a first outer layer made of a wear-resistant material,
• a laminate film according to the invention, wherein the side of the base layer of the laminate film faces the first outer layer.

In one embodiment, the first outer layer may be made of a material selected from, but not limited to, paper, polyethylene or polyamide-based sheets, ortho-phthalaldehyde-based sheets, or polyester-based sheets or combinations. It is preferred that the first outer layer is a combination of materials when using polyester-based layers.

In one embodiment, the first outer layer and the laminate film are laminated to provide the package. Lamination of the first outer layer to the laminate provides a strong laminate when examined for various properties, the package is easy to wrap, and it is ensured that the individual parts of the laminates forming the package do not fall apart.

In a further embodiment, the packaging further comprises a second outer layer, which faces the outer side of the first outer layer. Preferably, 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 the manufacturer of the product. It is also or alternatively contemplated that the first outer layer may be printed.

It is also contemplated that an adhesive may be applied between the second and first outer layers. The adhesive layer may be made of the same or different material as that of one of the tie layers.

Other suitable adhesives are adhesives approved for use in human packaging products and known to those skilled in the art. A suitable adhesive may be selected from, but not limited to, polyurethane based adhesives, epoxy based adhesives, or acrylic based adhesives.

The laminate of the present invention must be inert and impermeable to the compound that encloses the laminate. Therefore, in one embodiment of the invention, at most 10 wt%, preferably at most 5 wt%, even more preferably at most 1.5 wt%, most preferably 0.5 wt% of the compound is stored after 12 weeks of storage 40 ° C migrated into the laminate film.

In another embodiment, the laminate film encloses a compound selected from the group consisting of nicotine, rivastigmine, fentanyl, and lidocaine. These compounds are known as harsh chemicals / compounds and require special packaging.

1. a) gegebenenfalls eine Außenschicht bereitgestellt wird,
2. b) eine erfindungsgemäße Laminatfolie bereitgestellt wird,
3. c) eine Zusammensetzung, die eine Verbindung umfasst, auf die Seite der Kontaktschicht der Laminatfolie platziert wird, und
4. d) die Außenschicht und/oder die Laminatfolie auf eine solche Weise versiegelt werden, vorzugsweise durch Heißsiegeln, dass ein hohler Innenraum zum Versiegeln der Zusammensetzung entsteht, wobei der hohle Innenraum eine Innenseite und eine Außenseite aufweist, wobei die Innenseite der Folie die Kontaktschicht der Coextrusionsschicht ist und die Außenseite der Folie die Basisschicht und/oder die erste und zweite Außenschicht ist.

The invention also relates to a method of packaging a composition comprising a compound, the method comprising the steps of

1. a) optionally an outer layer is provided,
2. b) a laminate film according to the invention is provided,
3. c) a composition comprising a compound is placed on the side of the contact layer of the laminate film, and
4. d) the outer layer and / or the laminate film are sealed in such a manner, preferably by heat sealing, to form a hollow interior for sealing the composition, the hollow interior having an inside and an outside, the inside of the film being the contact layer of the coextrusion layer and the outside of the film is the base layer and / or the first and second outer layers.

It is contemplated that a first and / or second outer layer is laminated to the laminate film prior to steps c) and d), for example, in a combined coextrusion and lamination step.

In a preferred embodiment, the compound of the composition is selected from the group consisting of nicotine, lidocaine, rivastigmine and fentanyl. The composition containing the compound may be a patch, preferably a transdermal patch.

Packaging should preferably comply with international standards such as 16 CFR §1700.20 (for the USA) and ISO 8317 (2003), which the DIN EN ISO 8317 (2004) (for Europe). A "package" in the context of the invention is intended to mean an entire film or laminate used to package a chemical compound.

Certain laminate films of the present invention include, but are not limited to, the following specific examples of base layer / tie layers / contact layer (the last three being coextruded): Al / t-EBAMA / EMAA / COC, Al / EMA / EMAA / COC, Al / EBA / EMAA / COC, Al / EEA / EMAA / COC, Al / LDPE / EMAA / COC, AL / t-EBAMA / EAA / COC, AL / LDPE / EAA / COC, AL / EMA / EAA / COC, Al / EMA / t-EBAMA / COC, Al / EBA / t-EBAMA / COC, Al / EEA / t-EBAMA / COC, Al / EAA / EMAA / PA, Al / t-EBAMA / EMAA / PA, Al / EMAA / EMAA / PA, Al / EAA / t-EBAMA / PA, Al / EMAA / t-EBAMA / PA.

In one embodiment of the invention in which the tie layer contains ethylene-acrylic acid, the ethylene-acrylic acid preferably has an acrylic acid content of more than 8% by weight, preferably over 10% by weight, based on the weight of the ethylene-acrylic acid layer ,

Certain nicotine-resistant films of the invention include, but are not limited to, the following specific examples of base layer / tie layers / contact layer (the latter three being coextruded): Al / t-EBAMA / EMAA / COC, Al / EMA / EMAA / COC, Al / EBA / EMAA / COC, Al / EEA / EMAA / COC, Al / LDPE / EMAA / COC, AL / t-EBAMA / EAA / COC, AL / LDPE / EAA / COC, AL / EMA / EAA / COC, Al / EMA / t-EBAMA / COC, Al / EBA / t-EBAMA / COC, Al / EEA / t-EBAMA / COC, Al / EAA / EMAA / PA, Al / t-EBAMA / EMAA / PA, Al / EMAA / EMAA / PA, Al / EAA / t-EBAMA / PA, Al / EMAA / t-EBAMA / PA.

In one embodiment of the invention where the film is nicotine resistant and the contact layer is a COC and the base layer is aluminum, the tie layer is a multiple layer of a terpolymer of ethylene, acrylic ester, and maleic anhydride and an ethylene-methacrylic acid copolymer.

In one embodiment of the invention wherein the contact layer is a COC and the base layer is aluminum, the tie layer is a multiple layer of a terpolymer of ethylene, acrylic ester and maleic anhydride and an ethylene-methacrylic acid copolymer, the loading of acrylic ester and maleic anhydride is at most 8 g / m ² , preferably 4 g / m ² , the loading of ethylene-methacrylic acid is at most 8 g / m ² , preferably at most 6 g / m ² , more preferably at most 4 g / m ² , and the entirety of the bonding layer is at most 9 g / m ² .

In another embodiment of the invention wherein the film is nicotine resistant and the contact layer is a PA and the base layer is aluminum, the tie layer is a multi-layer of an ethylene-methacrylic acid copolymer wherein the loading of ethylene and methacrylic acid is at most 6 grams / m ² , preferably 3 g / m ² , and an ethylene-acrylic acid copolymer, wherein the loading of the ethylene-acrylic acid is preferably at most 9 g / m ² , preferably 3 g / m ² , and wherein the entirety of Compound layer is at most 9 g / m ² .

In yet another embodiment of the invention wherein the film is resistant to nicotine and the contact layer is an EVOH and the base layer is aluminum, the tie layer is a multiple layer of EVOH and / or a terpolymer of ethylene, acrylic ester and maleic anhydride.

Certain rivastigmine-resistant films of the present invention include, but are not limited to, the following specific examples of base layer / tie layers / contact layer (the latter three being coextruded): Al / t-EBAMA / EMAA / COC, Al / EMA / EMAA / COC, Al / EBA / EMAA / COC, Al / EEA / EMAA / COC, Al / LDPE / EMAA / COC, Al / t-EBAMA / EAA / COC, Al / LDPE / EAA / COC, Al / EMA / EAA / COC, Al / EMA / t-EBAMA / COC, Al / EBA / t-EBAMA / COC, Al / EEA / t-EBAMA / COC, Al / EAA / EMAA / PA, Al / t-EBAMA / EMAA / PA, Al / EMAA / EMAA / PA, Al / EAA / t-EBAMA / PA, Al / EMAA / t-EBAMA / PA.

In one embodiment of the invention wherein the film is resistant to rivastigmine and the contact layer is a COC and the base layer is aluminum, the tie layer is preferably a multiple layer of a terpolymer of ethylene, acrylic ester and maleic anhydride and an ethylene-methacrylic acid copolymer.

In another embodiment of the invention wherein the film is resistant to rivastigmine and the contact layer is a PA and the base layer is aluminum, the tie layer is preferably a copolymer of ethylene and acrylic acid or an ethylene-methacrylic acid copolymer.

Certain lidocaine-resistant films of the present invention include, but are not limited to, the following specific examples of base layer / tie layers / contact layer (the latter three being coextruded): Al / t-EBAMA / EMAA / COC, Al / EMA / EMAA / COC, Al / EBA / EMAA / COC, Al / EEA / EMAA / COC, Al / LDPE / EMAA / COC, Al / t-EBAMA / EAA / COC, Al / LDPE / EAA / COC, Al / EMA / EAA / COC, Al / EMA / t-EBAMA / COC, Al / EBA / t-EBAMA / COC, Al / EEA / t-EBAMA / COC, Al / EAA / EMAA / PA, Al / t-EBAMA / EMAA / PA, Al / EMAA / EMAA / PA, Al / EAA / t-EBAMA / PA, Al / EMAA / t-EBAMA / PA.

In one embodiment of the invention wherein the film is resistant to lidocaine and the contact layer is a COC and the base layer is aluminum, the tie layer is preferably a multiple layer of a terpolymer of ethylene, acrylic ester and maleic anhydride and an ethylene-methacrylic acid copolymer.

In another embodiment of the invention where the film is resistant to lidocaine and the contact layer is PA and the base layer is aluminum, the tie layer is a multiple layer of an ethylene-methacrylic acid copolymer and an ethylene-acrylic acid copolymer.

Certain fentanyl resistant films of the present invention include the following specific examples of base layer / tie layers / contact layer (the last three but not limited to Al / t-EBAMA / EMAA / COC, Al / EMA / EMAA / COC, Al / EBA / EMAA / COC, Al / EEA / EMAA / COC, Al / LDPE / EMAA / COC, Al / t-EBAMA / EAA / COC, Al / LDPE / EAA / COC, Al / EMA / EAA / COC, Al / EMA / t-EBAMA / COC, Al / EBA / t-EBAMA / COC, Al / EEA / t-EBAMA / COC, Al / EAA / EMAA / PA, Al / t-EBAMA / EMAA / PA, Al / EMAA / EMAA / PA, Al / EAA / t-EBAMA / PA, Al / EMAA / t -EBAMA / PA.

In one embodiment of the invention wherein the film is resistant to fentanyl and the contact layer is a COC and the base layer is aluminum, the tie layer is preferably a multiple layer of a terpolymer of ethylene, acrylic ester and maleic anhydride and an ethylene-methacrylic acid copolymer.

In another embodiment of the invention where the film is resistant to fentanyl and the contact layer is PA and the base layer is aluminum, the tie layer is preferably a multiple layer of a copolymer of ethylene and methacrylic acid and an ethylene-acrylic acid copolymer.

The invention should not be limited to the above combinations. Other combinations are within the scope of the invention.

Conveniently, the polymers useful in the present invention are commercially available and therefore readily available from a variety of suppliers, thereby providing cost efficient production.

list of figures

• 1 is a cross section of an embodiment of a chemically resistant film according to the invention.
• 2 is a cross section of another embodiment of a chemically resistant film according to the invention.
• 3 is a cross section of a laminate according to the invention.

Detailed description

The laminate film and packaging according to the present invention is intended for use in the packaging of very aggressive substances such as nicotine, rivastigmine, fentanyl or lidocaine, but the invention is not intended to be limited to these specific substances.

The term "film" or "laminate film" according to the invention contemplates a product comprising a base layer coated with a coextrusion layer comprising one or more tie layers and a contact layer or comprising a base layer comprising one or more Bonding layers and a contact layer is laminated.

A "package" in the context of the invention is intended to mean a finished laminate used to package a substance.

The term "very aggressive compound" is to be understood as a compound which is both very reactive with metals, acids, bases and functional groups such as ketones, alcohols, hydrocarbons and / or esters, and / or is volatile, as well easily migrated through barriers. Similarly, the term "aggressive chemical resistant film" means a film which, when in contact with an aggressive substance, does not migrate more than 1.5% by weight of the nominal content into the packaging material, or the US Pat 90 to 110% by weight of the aggressive chemical substance remains in the product compared to Barex® as Index 100.

The term "oxygen and water resistant" as used in the context of the present invention contemplates a material whose oxygen transfer rate (OTR) and / or water vapor transfer rate (WVTR) is not more than 1, preferably not more than 0.1 , is, as stated above. The term WVTR may also be referred to as Moisture Vapor Transfer Rate (MVTR). WVTR and MVTR are equivalent.

The term "mechanically wear-resistant material" as used to describe the first outer layer is to be understood as a material suitable for the manufacture of flexible packaging. The mechanically wear-resistant material may be selected from materials such as For example, but not limited to, polyethylene, polyamide based, ortho phthalaldehyde based, or polyester based, or combinations.

Furthermore, the mechanically wear resistant material, i. the first outer layer may be provided as a film which is biaxially oriented to impart a higher seal strength to the package. The term "biaxially oriented" should be understood to mean that the polymer film provided was stretched both longitudinally and transversely during manufacture.

The term "outside" is to be understood in its broadest sense. The term external environment is used to define the direction that faces the side facing the composition or compound to be sealed by the laminate or package of the present invention. This means that the term external environment is independent of whether additional layers are coated, laminated or otherwise bonded to the film. Thus, the word is used to specify which direction a side of a layer faces.

The various embodiments of the invention will now be illustrated with reference to the figures and examples.

With reference to 1 Now, a film of the invention will be described in more detail. The foil, 1 , is obtained by having a base layer, 2 a coextrusion layer, 5 containing a tie layer, 3 , and a contact layer, 4 , can be provided, wherein the coextrusion layer on one side of the base layer, 2 is coated and cured / adhered by the process of the invention. The base layer, 2 , and the coextrusion layer, 5 , define the laminate film according to the invention. As a result, the laminate film comprises a base layer, 2 , and a coextrusion layer, 5 where the base layer, 2 , intended to face the external environment, and the coextrusion layer, 5 , is intended to be facing the composition / compound to be sealed.

The coextrusion layer may be coated on the base layer of, for example, aluminum by a coextrusion system well known in the art to provide the coextrusion layer coated on the first side of the aluminum base layer. The coextrusion layer may be applied in an amount of at most 40 g / m ² , preferably at most 30 to 40 g / m ² .

The coextrusion is preferably carried out at a temperature of 240 to 330 ° C, particularly preferably 270 to 300 ° C. The speed of application / coating is in the range of 150 to 600 m / min. The equipment suitable for extruding and laminating films and laminates according to the invention can be obtained from Bobst.

In another embodiment, the tie layer comprises two layers, as in FIG 2 is shown. The laminate film, 1 , is obtained by having a base layer, 2 , then a coextrusion layer thereon, 5 , which is a two-layer bonding layer, 3 that a first layer, 3a , and a second layer, 3b , contains, and a contact layer, 4 , includes. The coextrusion layer is on one side of the base layer, 2 , coated according to the method of the invention and can harden / harden.

In the illustrated embodiment, the connection layer comprises 3 , two layers according to the invention. These layers can be made from EMAA as the first bonding layer, 3a , with a loading of 4 g / m ² and EAA as the second bonding layer, 3b , be prepared with a maximum load of 5 g / m ² so that the total loading of the tie layers does not exceed 9 g / m ² . The first layer of EMAA is the contact layer, 4 which is made, for example, of polyamide and has a loading of 9 to 27 g / m ² , facing, the second layer made of EAA is the base layer, 2 , facing.

The laminate film of the invention is intended for use as part of a package suitable for sealing a very aggressive substance. The foil can represent the packaging itself.

To further improve the mechanical wear resistance of the film, a first outer layer may be laminated to the base layer side of the film or simply wrapped around the film to provide a laminate. Consequently, in 3 a cross section of an embodiment of a laminate according to the invention, 12 , illustrates that a first outer layer, 21 , a base layer, 22 , and a coextrusion layer, 25 , includes. The first outer layer, 21 , and the base layer side, 22 , can be laminated together before, during or after the coextrusion layer, 25 , is applied to the base layer / coated.

The first outer layer, 21 , is a mechanically wear-resistant layer that adds safety features to the packaging, ensuring that the packaging is not accidentally opened. Therefore, the first outer layer may also be considered a parental control layer, which means that the first outer layer is made of a material and sealable in a way that is difficult for children to open. In addition, the outer layer may be provided with a second outer layer, 20 , to be provided.

The second outer layer, 20 is typically a paper layer with the paper layer facing the outside environment; the outward-facing side can be printed as desired. The second outer layer, such as a paper layer, is added to provide a printable platform for improving the rigidity of the package.

Moreover, it is within the inventive idea of the present invention that an adhesive is applied between the first outer layer and the base layer and / or between the first outer layer and the second outer layer. The obtained package can then be assembled in such a way that the various layers do not separate during handling, printing and / or packaging of the substance to be packaged.

After manufacture, the film, laminate or package may be stored in the form of rolls ready for further lamination or packaging of a composition to be packaged.

In use, the package is sealed around the composition to be packaged so that the contact layer of the coextrusion layer faces the inside and the composition, and the base layer, first outer layer or second outer layer, if applicable, faces the outer side, so that a hollow interior to the Recording the composition is created.

The sealing of the package is achieved in such a way that the contact layer of the coextrusion layer faces the composition so that the remaining part of the package is protected by the contact layer of the coextrusion layer. In this way, the composition is held inside the package and therefore has direct contact only with the contact layer of the coextrusion layer.

In general, the order in which the various layers of the package according to the invention are applied to the base layer is flexible. Therefore, the first outer layer may be applied before the coextrusion layer is added, and vice versa. The order depends on which production line is suitable in a particular situation.

In all aspects of the invention, the base layer may be selected from, but not limited to, a metal foil, preferably aluminum foil, a polymer such as a polymer made from polyamide, polyvinylidene chloride, silicon or alumina coated polyesters, and / or fluoropolymers, such as commercially available aluminum foil, for example of hydro or AlOx coated PET films, available e.g. from Toray Films Europe or SiOx coated PET films, available e.g. from Celplast under the trade name Ceramis.

In any aspect of the invention, each of the tie layers of the optional multilayer tie layer may be selected from a material selected from ethylene-methacrylic acid (EMAA), ethylene-acrylic acid (EAA), preferably an ethylene-acrylic acid having an acrylic acid content of at least 10 wt Total weight of the ethylene-acrylic acid (EAA), terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene, butyl acrylate and maleic anhydride (t-EBAMA), a terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene, butyl acrylate, maleic anhydride (t-EBAMA ) Terpolymer of ethylene, methacrylic acid and glycidyl methacrylate, ethylene-methyl acrylate (EMA), ethylene-butyl acrylate (EBA), ethylene-ethyl acrylate (EEA) or low-density polyethylene (LDPE).

Such polymers described above are available as commercial Lotader® 3410 products supplied by Arkema or Nucrel® 0609HSA sold by Dupont® or Escor ™ 6000 sold by ExxonMobil.

In all aspects of the invention, the contact layer may be made of a material selected from cycloolefin copolymer, a polyamide or an ethylene-vinyl alcohol, or mixtures thereof, such as the commercial products EVAL® C109B marketed by Kuraray, Selar PA 3426R distributed by Dupont® or COC 6013M-07, COC 8007F-600, 7010F-600 or 9506F500 sold by Topas® or EVOH available from Nippon Gohsei under the trade name Soarnel®.

In all aspects of the invention, the first outer layer may be made of a material selected from paper, polyethylene or polyamide based sheets, ortho-phthalaldehyde based sheets or polyester based sheets, or combinations such as from the commercial product F-PAP sold by Flexpet.

The invention will now be illustrated in more detail with reference to the following non-limiting examples.

RED calculation

The determination of HSP values and interaction radius for nicotine, rivastigmine, fentanyl and lidocaine requires that the solubility of the drug be tested against at least 16 solvents having a range of polar and hydrogen bonding properties. The methodology for determining HSP values, interaction radius and RED values are in CM Hansen: "Hansen Solubility Parameters, A User's Handbook", CRC Press, 2007 , Second Edition and described in the EP 2 895 531 illustrated.

Typical solvents used to determine HSP may include, but are not limited to, those contained in Table 4. Table 4: Typical solvents used to determine the HSP of a polymer or substance of interest Typical solvents used to determine the HSP of rivastigmine, lidocaine, fentanyl and nicotine Chemical name Trade name or alternative name acetonitrile acetonitrile Ethylene glycol n-butyl ether Butyl CELLOSOLVE ™ glycol ether dibutyl dibutyl dimethylformamide dimethylformamide dimethyl sulfoxide dimethyl sulfoxide methanol methyl alcohol 2-butanone methyl ethyl ketone 4-methyl-2-pentanone methyl isobutyl ketone n-butyl acetate n-butyl acetate n-heptane n-heptane 1-propanol n-propyl o-dichlorobenzene 1,2-dichlorobenzene tetrahydrofuran tetrahydrofuran toluene methylbenzene propylene carbonate propylene carbonate water water

To evaluate the solubility of rivastigmine, lidocaine, fentanyl and nicotine in the solvents, an experimental measurement can be made. The solubility is based on the visual observation of 0.5 g of the chemical substance in a sample vial with 5 cm ^{3 of} solvent rated at room temperature. The sample vessel is closed with a polyethylene-lined lid and labeled with the solvent contained. The sample vials are placed in a low speed vial shaker at room temperature. After 24 hours, the sample vials are removed from the sample vial shaker and allowed to rest for 30 minutes before being visually evaluated. The evaluation is performed by giving each solvent a score where 0 is insoluble and 1 is soluble. The numerical scores are then entered into the HSPiP software program to obtain the HSP (Hansen solubility parameter). R (radius) values for the relevant compound, eg nicotine, rivastigmine, fentanyl and / or lidocaine are entered and a report is generated.

The report lists the final parameters and R-values calculated for nicotine, rivastigmine, fentanyl and / or lidocaine. The report also lists the solvents used in the evaluation, their HSP values (taken from a database), the rating of the visual observations, and their RED values with a specific polymer of interest. Similarly, RED values can be calculated for other connections.

Examples

Examples 1 and 2 are embodiments of a film according to the invention. The film comprises a base layer joined to a tie layer comprising two layers (a first tie layer and a second tie coat), wherein the first tie layer layer is bonded to the contact layer. The film according to the invention has an ordered structure of:

Base layer / tie layer 2 / tie layer 1 / contact layer wherein the last three layers are coextruded by the process of the present invention to form a coextrusion layer.

In both examples, the coextrusion layer is co-extrusion coated onto the base layer such that the contact layer has a surface intended to be in contact with a composition containing a compound selected from nicotine, rivastigmine, fentanyl or lidocaine and wherein the composition is in the form of a transdermal patch may be present.

example 1

Example 1 is a film comprising COC (commercial product Topas® 8007F-600) as a contact layer with a loading of 22 g / m ² . The first layer of the multilayer tie layer is an ethylene-methacrylic acid copolymer (Nucrel® 0609HSA) with a loading of 4 g / m ² . The second layer of the multilayer tie layer is a terpolymer of ethylene, butyl acrylate and maleic anhydride (Lotader® 3410) with a loading of 4 g / m ² . The base layer is aluminum foil. The total loading of the multilayer bonding layer and the contact layer is 30 g / m ² .

The film had good mechanical properties, cf. below, and was easy to make.

Example 2

Example 2 is a film comprising PA (Selar® PA 3426R) as the contact layer with a loading of 8 g / m ² . The first layer of the tie layer is an ethylene-methacrylic acid copolymer (Nucrel® 0609HSA) with a loading of 4 g / m ² . The second layer of the tie layer is an ethylene-acrylic acid copolymer (Escor ™ 5110) with a loading of 4 g / m ² . The base layer is aluminum foil. The total loading of the multilayer bonding layer and the contact layer is 16 g / m ² .

The film had good mechanical properties, cf. below, and was easy to make.

Example 3

Example 3 is a film comprising COC (ethylene-1-norbornene copolymer, commercial product, Topas® 8007F-600) as a contact layer with different loadings of 22, 22 and 12, respectively, as shown below.

In a first film, the first layer of the tie layer was an ethylene-methacrylic acid copolymer (Nucrel® 0609HSA) with a loading of 4 g / m ² . The second layer of the tie layer was an ethylene-acrylic acid copolymer (Lotader® 3410) with a loading of 4 g / m ² . The base layer was aluminum foil. In a second and third laminate film, only one layer of the tie layer was contained.

When tested with nicotine as an API, the following was noted regarding the performance of the laminates. Table 5 Laminate # Connection 2 Connection 1 Contact Result, API recording 1 4 4 22 OK 2 8th 22 OK 3 18 12 Not OK* * Recording was higher than the specified upper limits.

Alternative commercial COC products include, but are not limited to, Topas® 9506F-500, Topas® 7010F-600 (API API, but requires higher welding temperatures than the other two).

Example 4

Similar to above, various laminate films were prepared, all of which included outer layers and a base layer to mimic a commercial product. The laminate films were produced with different applications of coextrudates according to the invention (comp.) And comparative extrudates, which are not part of the invention (cf.), as shown in Table 6.

• Verbindungsschicht 2: Nucrel® 0609HSA (eine Ethylen-Methacrylsäure)
• Verbindungsschicht 1: Escor® 5110 (eine Ethylen-Acrylsäure) Kontaktschicht: Selar® PA 3426R (ein Polyamid)

Tabelle 6 Folie #/ Auftrag g/m² Verbindungsschicht 2 Verbindungsschicht 1 Gesamt Verbindung Kontakt taktschicht Gesamt Auftrag 1 1 1 2 8 10 vergl. 2 3 3 6 8 14 erf. 3 4 4 8 8 16 erf. 4 7 7 14 12 26 vergl. 5 4 4 8 18 22 erf. 6 4 4 8 22 30 erf. 7 4 4 8 24 32 erf. 8 8 8 16 40 56 vergl. All laminate films were thus produced from PETW36 / PE14 / AL9 as outer layers and base layer. The coextruded layers were composed of

• Bonding Layer 2: Nucrel® 0609HSA (an ethylene-methacrylic acid)
• Bonding Layer 1: Escor® 5110 (an ethylene acrylic acid) Contact Layer: Selar® PA 3426R (a polyamide)

Table 6 Foil # / order g / m ² Connecting layer 2 Connecting layer 1 Total connection Contact contact layer Total order 1 1 1 2 8th 10 comp. 2 3 3 6 8th 14 erf. 3 4 4 8th 8th 16 erf. 4 7 7 14 12 26 comp. 5 4 4 8th 18 22 erf. 6 4 4 8th 22 30 erf. 7 4 4 8th 24 32 erf. 8th 8th 8th 16 40 56 comp.

Thus, films # 1, 4, and 8 were not in accordance with the invention because either 1) the contact layer was too thick (four times the tie layer), 4) the entire tie layer was too thick, and the bond / contact ratio was out of range ie the contact layer was too thin; and 8) the entire tie layer was too thick and the total load was too high, even though the bond / contact ratio was within the range.

method

• - Reißfestigkeit
• - Durchstoßfestigkeit auf beiden Seiten
• - Siegelfestigkeit
• - Laminierfestigkeit
• - Explorationstest

The mechanical properties of the laminate films of Table 6 were tested. The following properties have been tested:

• - tear strength
• - puncture resistance on both sides
• - Seal strength
• - Lamination strength
• - exploration test

• Reißfestigkeit - gemäß ASTM D1937-14 ohne Modifikationen.

All tests were conducted according to industry standards and with some modifications as follows:

• Tear resistance - according to ASTM D1937-14 without modifications.

Puncture resistance - according to ASTM F1306 with the following modifications: Sample diameter 48 mm instead of 34.9 and tip diameter of the penetration tool 3.0 mm instead of 3.2 mm. The resistance should be at least 50 N.

• Versuch 1: 150°C, 5 bar Druck, 0,5 Sekunden
• Versuch 2: 180°C, 5 bar Druck, 0,5 Sekunden
• Versuch 3: 150°C, 5 bar Druck, 0,1 Sekunde

Seal strength according to DIN 55529 without modifications.
The seal strength test consisted of three tests:

• Experiment 1: 150 ° C, 5 bar pressure, 0.5 seconds
• Experiment 2: 180 ° C, 5 bar pressure, 0.5 seconds
• Trial 3: 150 ° C, 5 bar pressure, 0.1 second

Lamination strength according to ASTM D903-98 (2010) with the following modifications: Sample width was 15 mm instead of 25 mm, samples were not conditioned at 23 ° C ± 1 ° C, 50% RH ± 2%. Instead, all samples were stored in the same location and thus kept under identical conditions.

The pulling speed was set to 100 mm / min instead of 305 mm / min. The measuring angle was 90 ° and not 180 °.

The exploration strength test was conducted as follows: A four-side sealed pocket measuring 80mm x 90mm including a 5mm wide seal area was sealed with settings of 150 ° C, 0.3 seconds and 3 bar pressure.

The bag was held between two pieces of iron with a gap of 5 mm and was penetrated with a syringe connected to a printing device. The bag was then inflated to a pressure of 0.4 bar.

The success criterion for a particular laminate is to withstand the pressure for 40 seconds without bursting.

The results of all tests performed are given in Table 7. Table 7 No. Coating loading (g / m ² ) Tensile strength (machine direction) (N) Tear strength (transverse direction) (N) Puncture resistance front side (N) Puncture resistance sealing side (N) Laminating resistance (N / 15 mm) Seal strength # 1 (N / 15 mm) Seal strength # 2 (N / 15 mm) Seal strength # 3 (N / 15 mm) exploration test 1 10 0.7 0.4 65.8 58.9 1.5 8.0 7.6 7.6 OK 2 14 0.9 0.5 70.4 62.0 5.1 8.7 9.2 9.3 OK 3 16 0.7 0.5 68.8 65.7 > 5 10.8 10.3 9.9 OK 4 26 0.8 0.6 71.1 72.3 4.5 16.4 15.4 12.0 OK 5 22 0.7 0.4 71.6 70.4 2.2 15.7 13.9 14 OK 6 30 1.2 0.5 67.6 67.9 3.7 16.6 16.9 11.9 OK 7 32 0.8 0.5 76.1 73.2 2.4 19.9 17.5 9.5 OK 8th 56 1.1 0.9 84.2 88.3 1.7 26.5 23.7 No seal error

discussion

Tear strengths of 0.7 to 1.2 indicate that the major factor influencing this property is the substrate to which the coating is applied, i. the base layer and outer layers since there is no significant increase after the coating weight increase.

When considering the puncture resistance, Samples 1 to 7 showed a puncture strength of 65.8N to 76.1N (front side) and 58.9N to 73.2N (sealing side), whereas Sample 8 with the very thick coating showed an increase 84.2 and 88.3, respectively. It was surprising to find that even with such a thin loading of only 10 g / m ² (Sample 1) mechanical properties were achieved at the same level as with larger loadings. However, increasing the total loading of the tie layer to 16 g / m ² and the total load to 56 increased the puncture resistance, although the impact on tear strength was significantly lower. As a result, in this test, the upper limits had an effect on the properties.

Sample 1 exhibited a lamination strength of 1.5 N / 15 mm. Since there only 1 g / m ² of each tie layer was loaded, the lowest lamination strength that is too low to be acceptable, with about 2 being the least acceptable for the purpose. Example 2 also had a low loading of the tie layers which is generally lower than that described in the prior art, but surprisingly, these samples exhibited laminating strengths of the same order of magnitude as samples 3 to 7 above the acceptable threshold of about 2 It is expected that Sample 8 with the highest total loading will have the highest lamination strength, which surprisingly did not prove to be the case. Without wishing to be bound by theory, it is believed that in order to apply such high loadings, the melt is allowed to cool in the air gap, thereby reducing the lamination strength.

With respect to seal strength, the results show, to some extent, an increase in seal strength with an increase in the contact layer portion of the coextrudate. As the layer becomes too thick, more energy is needed to seal, and as a result, sample 8 does not seal properly under all ordinary conditions. Sample No. 8 therefore has a narrow processing window, which limits machine settings in production.

This observation was also confirmed by the exploration test, in which Sample No. 8 failed as the only sample. Sample 7 worked well in the seal test despite the high load and as well as samples 1 to 6.

In summary, from the combined results of the mechanical tests, it could be seen that Samples 1 and 8 did not meet all the requirements because the respective lamination strengths were too low. Therefore, it seems that there is a limit to the relationship between bonding layers and contact layers as claimed. It can also be seen from the tests that there is an upper limit for the total layers.

It is a requirement of the invention that the tie layer (s) are not thicker than the contact layer, as the experiments have shown that the laminate used in such cases takes up too much API, cf. Example 3. Thus, even if Sample 4 has satisfactory mechanical properties, the uptake will be too high and the laminate sample can not be used as intended.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 0044559 [0006]
• WO 2017/114922 [0007]
• WO 2015/123211 [0008]
• EP 2895531 [0142]

Cited non-patent literature

• ISO 8317 [0094]
• DIN EN ISO 8317 [0094]
• C.M. Hansen: "Hansen Solubility Parameters, A User's Handbook", CRC Press, 2007 [0142]

Claims (11)

A laminate film comprising at least one base layer, which is water and / or oxygen resistant, and a coextrusion layer containing a tie layer and a contact layer, wherein the contact layer is a polymer selected from the group consisting of a cycloolefin copolymer, a polyamide, or an ethylene Vinyl alcohol, wherein the total loading of the tie layer is in the range of 3 to 9 g / m ² and wherein the loading of the contact layer loading _contact = x * loading is _compound , where x is in the range of 1 to 3, particularly preferably 1.33 to 2.75, wherein the contact layer is the innermost layer and is capable of facing a composition which is packaged in the film. Laminate film after Claim 1 in which the tie layer is a multilayer tie layer comprising at least two layers. Laminate film after Claim 1 and 2 in which at least one layer of the multilayer tie layer is made of a material selected from ethylene-methacrylic acid, ethylene-acrylic acid, terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene, butyl acrylate and maleic anhydride, or a combination thereof. Laminate film after Claim 2 or 3 in which a second layer of the multilayer tie layer is a material selected from the group consisting of ethylene-methacrylic acid, low density polyethylene, ethylene-methyl acrylate, ethylene-butyl acrylate, ethylene-ethyl acrylate, a terpolymer of ethylene, acrylic ester and maleic anhydride, preferably ethylene, butyl acrylate and maleic anhydride, ethylene-acrylic acid, preferably an ethylene-acrylic acid having an acrylic acid content of more than 10% by weight with respect to the total weight of the ethylene-acrylic acid layer, or a combination thereof. Laminate film according to one of the preceding claims, in which the bonding layer consists of two layers, a first bonding layer and a second bonding layer. Laminate film after Claim 5 in which the loading of the first and second tie layers is about 1: 1 (weight / weight). Laminate film after Claim 5 or 6 in which the loading is _contact = x * loading _compound , where x is in the range of 1.33 to 2.75. Laminate film after one of Claims 1 to 7 in which the base layer is selected from the group consisting of a metal foil, preferably aluminum foil, polymers, such as polyamide, polyvinylidene chloride, silicon or aluminum oxide-coated polyesters, and / or fluoropolymers. Packaging for packaging a composition comprising at least: - a first outer layer made of a mechanically wear-resistant material, - a laminate film according to any one of Claims 1 to 8th in which the side of the base layer of the film faces the first outer layer. Packaging after Claim 9 in which the laminate encloses a composition containing a compound selected from nicotine, rivastigmine, fentanyl and lidocaine. Packaging after Claim 9 or 10 in which the composition is a patch, preferably a transdermal patch.

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