Method for providing an extreme chemical resistant film, a film and laminate obtainable therefrom

Abstract

The present disclosure relates to a method for providing a film. The method may include providing a base layer, wherein the base layer is resistant to one or more of water or oxygen; coextruding a tie layer and a contact layer to provide a coextrusion layer; coating the coextrusion layer to the base layer; allowing the coextrusion layer coated to the base layer to adhere to form the film, wherein the film comprises the tie layer and the contact layer formed as a coextrusion layer coated to the base layer; wherein the tie layer comprises one or more layers, and wherein the tie layer, or the one or more layers of the tie layer, has a loading in the range of 7 to 20 g/m.sup.2; wherein the contact layer comprises a cycloolefin copolymer (COC).

Claims

1. A method for providing an aggressive chemical-resistant film, wherein the film is resistant to a chemical selected from nicotine, fentanyl, rivastigmine, or lidocaine, said method comprising: providing a base layer, wherein the base layer comprises aluminum and is resistant to one or more of water or oxygen; coextruding a tie layer and a contact layer to provide a coextrusion layer, wherein the contact layer consists of a cycloolefin copolymer (COC); coating the coextrusion layer consisting of the tie layer and the COC of the contact layer directly to the base layer comprising the aluminum; and allowing the coextrusion layer coated to the base layer to adhere to form the aggressive chemical-resistant film, wherein the aggressive chemical-resistant film consists of: the base layer comprising the aluminum, and the coextrusion layer consisting of the tie layer, and the contact layer consisting of COC, wherein the tie layer comprises one or more layers, and wherein the tie layer, or the one or more layers of the tie layer, has a loading in the range of 7 to 20 g/m.sup.2.

2. The method according to claim 1, wherein a melting point of the tie layer differs from a melting point of COC by 30° C. or less.

3. The method according to claim 2, wherein the melting point of the tie layer differs from the melting point of COC by a value in the range of 5−15° C.

4. The method according to claim 1, wherein the contact layer has a loading in the range of 4 to 20 g/m2.

5. The method according to claim 1, wherein a loading of an entirety of the tie layer is in the range of 7 to 20 g/m2.

6. A method according to claim 1, wherein a loading of at least a portion of the tie layer is in the range of 7 to 20 g/m2.

7. The method according to claim 1, wherein the one or more layers of the tie layer comprises a plurality of layers, and wherein a loading of the plurality of layers is in the range of 7 to 20 g/m2.

8. The method according to claim 1, wherein the one or more layers of the tie layer consists of two layers.

9. The method according to claim 1, wherein coating the coextrusion layer to the base layer comprises performing a coextrusion coating.

10. The method according to claim 1, wherein at least one of the one or more layers of the tie layer comprises an acrylic acid layer or a polyethylene layer.

11. The method according to claim 1, wherein the one or more layers of the tie layer comprises an acrylic acid layer and a polyethylene layer.

12. The method according to claim 11, wherein the acrylic acid layer comprises ethylene acrylic acid.

13. A method for providing a laminate, wherein the laminate comprises an aggressive chemical-resistant film, said method comprising: providing a base layer, wherein the base layer comprises aluminum and is resistant to one or more of water or oxygen; coextruding a tie layer and a contact layer to provide a coextrusion layer, wherein the contact layer consists of a cycloolefin copolymer (COC); coating the coextrusion layer consisting of the tie layer and the COC of the contact layer directly to the base layer comprising the aluminum; and allowing the coextrusion layer coated to the base layer to adhere to form the aggressive chemical-resistant film, wherein the aggressive chemical-resistant film consists of: the base layer comprising the aluminum, and the coextrusion layer consisting of the tie layer, and the contact layer consisting of COC, wherein the aggressive chemical-resistant film is resistant to a chemical selected from nicotine, fentanyl, rivastigmine, or lidocaine, wherein the tie layer comprises one or more layers, and wherein the tie layer, or the one or more layers of the tie layer, has a loading in the range of 7 to 20 g/m.sup.2.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1 is a cross section of an embodiment of a chemical resistant film according to the disclosure.

(2) FIG. 2 is a cross section of another embodiment of a chemical resistant film according to the disclosure.

(3) FIG. 3 is a cross section of a laminate according to the disclosure.

(4) FIG. 4 shows the results of an absorption study of rivastigmine as API wrapped in laminates according to the disclosure as compared to a commercial available laminate with the commercial available polymer film Barex® after storing for 2, 4, 8 and 12 weeks at 40° C.

(5) FIG. 5 shows the amount of licodaine remaining in a patch after 7 days at 40° C. for embodiments of the laminate according to the disclosure and in comparison, with a commercial available Barex® laminate.

DETAILED DESCRIPTION

(6) The disclosure will now be described in greater details. Each specific embodiment and variation of features applies equally to each aspect of the disclosure unless specifically stated otherwise.

(7) The film, laminate and packaging according to the present disclosure is intended to be used in packaging highly aggressive substances such as nicotine, rivastigmine, fentanyl or lidocaine, however, the disclosure should not be limited to these specific substances.

(8) The term “film” according to the disclosure contemplates a product comprising a base layer coated with a coextrusion layer comprising a tie layer and a contact layer or a base layer laminated with a tie layer and a contact layer.

(9) Where the contact layer is laminated, for example using an EVOH film, the contact layer and tie layer may be either coextruded, or, the contact film layer may be laminated to the base layer optionally with an intermediate tie layer or the tie and contact layers may be the same material.

(10) The term “laminate” according to the disclosure contemplates the film to which a further layer is laminated, such as a first outer layer.

(11) A “packaging” is in the context of the disclosure intended to mean a film or laminate used to pack a substance. Packaging may be used interchangeably for film or laminate.

(12) The term “highly aggressive substance” should be understood as a substance which is both very reactive with metals, acids, bases or functional groups such as ketones, alcohols, hydro carbons and/or esters, and/or, volatile but also easily migrates through barriers. Similarly, the term “aggressive chemical resistant film” means a film which when in contact with an aggressive substance does not allow more than 1.5% w/w of nominal content to migrate to the packaging material or that 90-110% w/w of the aggressive chemical substance remains in the product when compared to Barex® as index 100.

(13) Therefore, the films, laminates or packagings applicable for packing highly aggressive substances should have both chemical-resistant properties but also limit the migration of the aggressive substance through the film, laminate or packaging. The aggressive substance according to the disclosure is also or alternatively susceptible to degradation when exposed to ambient conditions, such as oxygen and water, it is volatile and able to migrate or a combination. Specifically, the aggressive substance is selected from but not limited to nicotine, oils, such as spearmint and peppermint oil, licodaine, fentanyl or rivastigmine.

(14) The term “oxygen and water resistant” as used in the context of the present disclosure 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 also indicated above. The term WVTR may also be referred to as the moisture vapor transfer rate (MVTR). WVTR and MVTR are equivalent.

(15) The term “mechanically wear resistant layer” as used for the first outer layer in the context of the present disclosure should be a material which is suitable for the manufacture of a flexible packaging. The mechanically wear resistant layer may be chosen from materials such as polyethylene or polyamide based sheets, ortho-phthalaldehyde based sheets, or polyester based sheets or combinations.

(16) Further, the mechanically wear resistant material can be provided as a film that is biaxially oriented to give the film higher seal strength. The term “biaxial oriented” should be understood such that the provided polymer film has been stretched in both a longitudinal and a transverse direction during manufacturing.

(17) The term “exterior side” should be understood in its broadest term. The term exterior environment is used for defining the direction opposite of the side that is facing the highly aggressive substance to be sealed by a laminate or packaging of the present disclosure. This means that the term exterior environment is independent on whether additional layers are coated, laminated or otherwise attached to the film. Thus, the word is used for specifying which direction a side of a layer is facing.

(18) The various embodiments of the disclosure will now be illustrated with references to the figures and examples.

(19) With reference to FIG. 1 a film of the disclosure will now be described in greater detail. The extreme chemical resistant film, 1, is obtained by providing a base layer, 2. A coextrusion layer, 5, comprising a tie layer, 3, and a contact layer. 4, is coated to one side of the base layer, 2, according to the method of the disclosure and is allowed to adhere. The base layer, 2, and the coextrusion layer, 5, define the film according to all the aspects of the disclosure. Consequently, the film is provided with a base layer side. 2, and a coextrusion layer side 5, wherein the base layer side. 2, is intended for facing the exterior environment and the coextrusion layer side, 5, is intended for facing the highly aggressive substance to be sealed.

(20) The coextrusion layer may be coated to the aluminium layer by a coextrusion system generally known in the art to provide the coextrusion layer coated on the first side of the aluminum layer. The coextrusion layer may be applied in an amount of 7-40 g/m3. After coating of the aluminium layer and subsequently cooling, the coextrusion layer is adhered to the side of the tie layer facing away from the aggressive chemical substance.

(21) The coextrusion is preferably performed at a temperature of 240-330° C., more preferred 270-300° C. and the speed of the 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 disclosure may be obtained from Bobst.

(22) When using coextrusion, it is possible to obtain a multi layer which is thinner than multilayer layers provided by sequential film application techniques without compromising the extreme chemical resistance properties of the first laminate. Hence, the present disclosure does not only provide an extreme chemical resistance laminate, and packaging comprising the same but at the same time the manufacturing process is more cost effective since less polymer, forming the contact layer, has to be used.

(23) Another embodiment of a film in which the tie layer comprises two layers is illustrated in FIG. 2. The extreme chemical resistant film. 1, is obtained by providing a base layer, 2. The coextrusion layer, 5, comprises a tie layer, 3, comprising a first layer, 3a, and a second layer, 3b, and a contact layer 4. The coextrusion layer is coated onto one side of the base layer, 2, according to the method of the disclosure and is allowed to dry.

(24) In the embodiment illustrated, the tie layer, 3, comprises two layers. These layers may be made of EAA as the first layer, 3a, and polyethylene (PE) as the second layer, 3b, where the first layer of EAA faces the base layer and second layer of the PE faces the contact layer, 4.

(25) The extreme chemical resistant film according to the disclosure is intended for use as a component of a packaging suitable for sealing a highly aggressive substance. The film may constitute the packing itself.

(26) 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 be wrapped around the film to provide a laminate. Hence, in FIG. 3 is illustrated a cross section of an embodiment of a laminate according to the disclosure. 12, comprising a first outer layer. 21, a base layer, 22, and a coextrusion layer, 25. The first outer layer, 21 and the base layer side, 22, may be laminated together before, during or after the coextrusion layer 25 is applied/coated to the base layer.

(27) The first outer layer, 21, is a mechanically wear resistant layer which adds safety properties to the wrapping ensuring that the wrapping is not inadvertently opened. Hence, the outer layer can also be seen as a child proof layer meaning that the layer is made of a material and is sealable in such a way that it is difficult for children to open. Additionally, the outer layer may be provided with a second outer layer, 20.

(28) The second outer layer, 20, is typically a paper layer, wherein the paper layer is facing the exterior environment; the exterior facing side of the second layer may be printed as desired. The second outer layer, such as the paper layer is added to improve the stiffness of the packaging in addition to providing a printing platform.

(29) Furthermore, it is within the inventive concept of the present disclosure that an adhesive agent 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 packaging may then be assembled in such a way that the various layers do not part during handling, printing and/or packaging of the substance to be packed.

(30) After production, the film, laminate or packaging may be stored as rolls ready for use in further lamination or packaging of the aggressive substance to be packed.

(31) In use, the packaging is sealed around the substance to be packed so that the contact layer of the coextrusion layer faces the interior side and the substance, and, the base layer, first outer layer or second outer layer, as applicable, face the exterior side, so as to create a hollow interior for containing the, substance, such as the aggressive substance.

(32) The sealing of the packaging is achieved in such way that the contact layer of the coextrusion layer is facing the aggressive substance so that the remaining part of the package is protected by the contact layer of the coextrusion layer. In this way, the aggressive substance is encompassed by the inner side of packaging and will therefore only have direct contact with the contact layer of the coextrusion layer.

(33) In general, the order in which the different layers of the packaging according to the disclosure are applied to the base layer is flexible. Hence, the first outer layer may be applied before the coextrusion layer and the other way around. The order depends on which production line is suitable in a specific situation.

(34) In more details the packaging according to the present disclosure may in one embodiment be manufactured by obtaining a film comprising a base layer, such as an aluminum layer and a coextrusion layer comprising a biopolymer of ethylene and acrylic acid as a tie layer and EVOH as the contact layer coated to the aluminium as described above. The base layer side of the film may then be provided with an adhesive agent and subsequently laminated to a biaxial orientated PET-film which is the first outer layer, i.e. the mechanically wear resistant layer. The PET-film is further provided with an adhesive agent on the exterior side of the mechanically wear resistant layer and is subsequently laminated to a paper layer for providing the final packaging.

(35) An aggressive substance, such as but not limited to lidocaine, is placed on the contact layer side of the laminate which is welded around the substance, such as to form a pouch with an inner side and an outer side. Accordingly, the interior of the pouch consists of the coextrusion layer, where the contact layer of EVOH facing the aggressive substance thereby protects the rest of the provided packaging and the exterior side is the paper layer.

(36) In general, the lamination procedure for laminating the mechanically wear resistant or paper layer to each other or to the base layer is routine procedure for the person skilled in the art.

(37) According to all aspects of the disclosure 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, silicium or aluminium oxide coated polyesters, and/or fluro polymers, such as commercial Alu foil from e.g. Hydro, or AlOx coated PET films obtainable from e.g. Toray Films Europe, or SiOx coated PET films obtainable from e.g. Celplast under the tradename Ceramis.

(38) According to all aspects of the disclosure the tie layer may be made of a material selected from but not limited to a copolymer made of a material selected from a copolymer of ethylene and acrylic acid, ethylene and methacrylic acid and a terpolymer comprising ethylene, acrylic ester and a third polymer, which third polymer is preferably a glycidyl methacrylate, and more preferably a maleic anhydride, such as the commercial product Lotader® 3410 sold by Arkema or Nucrel® 0609HSA sold by Dupont®.

(39) According to all aspects of the disclosure the contact layer may be made of a material selected from cyclic olefin copolymer, a polyamide, or, an ethylene vinyl alcohol 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, or 9506F500 sold by Topas® or EVOH obtainable from Nippon Gohsei under the tradename Soarnel.

(40) According to all aspects of the disclosure 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 the commercial product F-PAP sold by Flexpet.

(41) The disclosure will now be illustrated in more details with reference to the following non limiting examples.

(42) RED Calculation

(43) Determination of the HSP values and interaction radius for nicotine, rivastigmine, fentanyl and lidocaine requires 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 deter-mining HSP values, interaction radius and RED values are described in C. M. Hansen: “Hansen Solubility Parameters, A User's Handbook”, CRC Press, 2007, Second Edition and exemplified in EP 2 895 531.

(44) Typical solvents used to determine the HSP may be but is not limited to the solvents present in table 2.

(45) TABLE-US-00002 TABLE 2 Typical solvents used to determine the HSP of a polymer or substance of interest. Typical solvents used in Determining of HSP of rivagstigmine, lidocaine, fentanyl and nicotine Chemical name Trade Designation or Alternate Name Acetonitrile Acetonitrile Ethylene glycol n-Butyl Ether Butyl CELLOSOLVE ™ Glycol Ether Dibutyl Ether Dibutyl Ether Dimethyl Formamide Dimethyl Formamide 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 l-Propanol n-Propyl Alcohol o-Dichlorobenzene 1,2-Dichlorobenzene Tetrahydrofuran Tetrahydrofuran Toluene Methylbenzene Propylene Carbonate Propylene Carbonate Water Water

(46) For assessing the solubility of Rivastigmine, Lidocaine, fentanyl and nicotine in the solvents an experimental measurement is performed. The solubility is assesed based on the visual observation of 0.5 g of the chemical substance in a vial with 5 cm3 solvent at room temperature. The vial is capped with a polyethylene-lined lid and labeled with the solvent loaded. The vials are placed in a vial shaker at low speed at room temperature. After 24 hours, the samples are removed from the vial shaker, and allowed to sit for 30 min before they are visually rated. The rating is performed by giving each solvent a score being 0 for insoluble and 1 for soluble. The numerical ratings are then entered into the HSPiP software program to obtain the HSP (Hansen solubility parameters). R (radius) values for the compound of relevance, e.g. nicotine, rivastigmine, fentanyl and/or lidocaine is inserted, 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.

Example 1—Performance of a Laminate According to the Disclosure Compared to a Commercially Used Laminate

(47) A study was conducted to evaluate the performance of four laminates according to the present disclosure as compared to a commercially available laminate product comprising Barex® as the contact layer.

(48) The wrappings according to the disclosure were compared to the performance of a Barex® laminate currently used in the field.

(49) The test is a resistance test, wherein the migration of rivastigmine to the laminates is evaluated.

(50) TABLE-US-00003 TABLE 3 The composition of the 6 wrappings was a follows, laminates 1 to 5 are laminates according to the disclosure First Second Adhesive/Polymer layer Base outer Outer Coextrusion layer layer layer layer Commercially Adhesive/Barex ® film Al PET Paper used Barex ® laminate (prior art) Laminate 1 Tie layer: Bipolymer of Al PET ethylene and acrylic acid (Nucrel 0609 HAS) Contact layer: PA (Selar PA 3426R) Laminate 2 Tie layer: Terpolymer of Al PET ethylene, acrylic ester and maleic anhydride (Lotader 3410) Contact layer: EVOH 60% (EVAL C109B) and PE 40% Laminate 3 Tie and contact layer: Al PET EvOH film (EVAL C109B) Laminate 4 Tie layer: Terpolymer of Al PE PET ethylene, acrylic ester and maleic anhydride (Lotader 3410) Contact layer: EVOH 100% (EVAL C109B) Laminate 5 Tie layer: Terpolymer of Al PE PET ethylene, acrylic ester and maleic anhydride (Lotader 3410) Contact layer: COC *Between the paper/PET, PET/Al, and Al/EVOH film layers an adhesive was applied.

(51) Laminates 1 to 5 were obtained according to the method of the disclosure. For laminates 1, 2, 4 and 5 a coextrusion layer was coated to the base layer and in laminate 3 the combined tie and contact layer was laminated to the base layer. For the co-extrusion layers, the loading of the tie layers was between 4-18 g/m2 and the loading of the contact layer was 8-12 g/m2.

(52) The resulting laminates were wrapped around a patch containing rivastigmine as API and the migration of the API to the packaging material/wrapping was measured after 2, 4, 8 and 12 weeks at 40° C. The API in the wrapping was measured by extracting the packaging and analysing the amount of API therein using Mass spectrometry.

(53) The Rivastigmine patches tested were commercially available patches originally containing 9.5 mg API/patch.

(54) The results are shown in FIG. 4 illustrating the resulting migration of rivastigmine (weight API extracted from the laminate) to the laminate in percentage of the content of the original patches of 9.5 mg.

(55) The columns are denoted 1, 2, 3 and 4 respectively to the order they are shown from left to right in FIG. 4. Hence column 1 (furthest to the left) for each contact layer polymer used shows the results for the 6 laminates after two weeks. Column 2 shows the results for the 6 laminates after four weeks. Column 3 shows the results for the 6 laminates after 8 weeks, and column 4 shows the results for the 6 laminates after 12 weeks.

(56) The Barex® laminate is a reference known for applicability in the art and comparison were made for evaluating the properties of the laminates according to present disclosure.

(57) From the figure it is clear that the results for laminates according to the disclosure obtained by coextrusion of either of EVOH, PA, or COC as well as laminating EVOH provides for an improved chemical resistant laminate compared to the commercially used Barex® laminate, meaning that less migration occurs.

(58) Also, a contact layer, illustrated as laminate 2, of a blend of EVOH and PE was prepared and tested. Though the properties of this blend with rivastigmine as API resulted in a higher migration of the API than Barex®, the rate is still below the limit demanded in the industry and hence, it illustrates that blends as provided in laminate 2 are usable alternatives to Barex®, as well. Surprisingly though the tie/contact layer made of 100% EVOH was markedly superior to the blend.

(59) Also, a contact layer, illustrated as laminate 3, a film of EVOH laminated to aluminum was prepared and tested. Surprisingly, it was shown that the use of EVOH in the form of a film laminated to aluminum provided a chemical resistant laminate.

Example 2—Stability Test of a Chemical Substance Wrapped in Laminates According to the Disclosure and Wrapped in a Prior Art Product Using Barex®

(60) Similar to the test described in example 1, laminates according to the disclosure were prepared as outlined in table 4 below. A lidocaine patch containing 40 mg lidocaine was wrapped in the pouch, packaged and stored at 40° C. for seven days.

(61) TABLE-US-00004 TABLE 4 Packagings for lidocaine stability test. Barex Commercially used COC coex same as Coex EVOH same as Barex ® laminate laminate 5 of laminate 4 of (prior art) example 1 example 1

(62) Stability of the API is important to ensure that the dose indicated on the packaging is correct. A value of 90%-110% of the original dose after one week when stored at 40° C. using Barex® as index 100 is considered acceptable. FIG. 5 illustrates the results of the test where the y-axis indicates the weight decrease of the two laminates according to the disclosure using Barex as index 100.

(63) As can be seen from FIG. 5, both inventive laminates have a lower value than the index 100 Barex®, comparative product, however with a value within the acceptable limits. The lower % value of the laminates according to the disclosure indicates that more lidocaine has disappeared from the patch.