APPLICATION AID FOR ORAL THIN FILM

Description

[0001] The invention relates to a composite comprising an oral thin film and an application aid for the oral thin film, a method for its production, and the composite for use as a medicinal product.

[0002] Oral thin films are thin films, usually containing a pharmaceutically active ingredient, that are placed directly in the oral cavity or applied to the oral mucosa, where they dissolve. These are primarily thin, polymer-based films containing the active ingredient, which, when applied to a mucous membrane, especially the oral mucosa, release the active ingredient directly into it. These oral thin films are generally non-sticky. The excellent blood supply of the oral mucosa ensures rapid absorption of the active ingredient into the bloodstream. This delivery system has the advantage that the active ingredient is largely absorbed through the mucosa, thus avoiding the "first-pass metabolism" that occurs with conventional tablet-based medications, which are usually taken with liquid and can be disadvantageous.The active ingredient can be dissolved, emulsified, or dispersed in the film. Suitable active ingredients can also be swallowed after the oral thin film dissolves in the mouth and thus absorbed via the gastrointestinal tract.

[0003] The application of oral thin films can be problematic. Difficulties can arise due to the shape, size, properties, and intended application site of the oral thin film, as well as user impairments, preventing proper application to the desired location. This is particularly important for oral thin films equipped with microneedles to enhance drug delivery to a surface; in such cases, it is crucial that these microneedles are not damaged before application.

[0004] WO 2019 / 101798 A1 concerns a multilayer oral drug film comprising at least two non-adhesive layers, each containing at least one hydrophilic polymer, and at least one water-soluble adhesive layer containing at least one water-soluble polymer and at least one plasticizer.

[0005] WO 2021 / 123289 A1 concerns a multilayer oral thin film comprising a matrix layer containing at least one polymer and at least one pharmaceutical active ingredient, and at least one carrier layer.

[0006] WO 2007 / 116959 A1 relates to a microneedling device comprising a plurality of microneedles on a substrate capable of piercing skin, wherein the surface of the microneedles and / or the substrate is partially or completely coated in a solid state with a coating carrier containing polyvinyl alcohol.

[0007] WO 2020 / 169667 A1 concerns an applicator with a handle and with a pressure body connected to the handle for a microneedle patch, as well as a unit consisting of such an applicator and a microneedle patch with a plurality of microneedles.

[0008] WO 2004 / 009172 A1 concerns microneedle devices having a frustoconical shape, microneedle insertion devices and methods for using microneedle devices.

[0009] WO 02 / 066016 A2 concerns a mucoadhesive medicinal preparation for the administration of active substances in veterinary or human medicine, with at least one active substance, characterized by the fact that the preparation has a mucoadhesive matrix that is disintegrable in aqueous media.

[0010] WO 2019 / 115815 A1 concerns a microneedle array, in particular an applicator system, and its use for the intradermal application of active substances in the form of salts, in particular medicinal products in the form of salts.

[0011] EP 2 389 940 A2 relates to a vaginal applicator comprising at least one first storage unit containing at least one mucopolysaccharide and at least one second storage unit containing at least one acid.

[0012] US 2018 / 177991 A1 concerns a microneedle applicator for inserting microneedles into the skin and delivering a drug into the skin.

[0013] While conventional application aids can provide some improvement, they are usually difficult to remove from the oral thin film and / or have a complicated design. Furthermore, there is a risk that the user may accidentally swallow the application aid.

[0014] The present application therefore addressed the task of providing an application aid for an oral thin film that overcomes the aforementioned disadvantages. The application aid should exhibit high haptic stability to ensure the oral thin film is applied to the desired location. Furthermore, the risk of ingesting the entire application aid should be minimized, as should the risk of the user damaging or destroying the oral thin film prior to application.

[0015] This problem was surprisingly solved with a composite according to claim 1, in particular with a composite comprising an oral thin film and an application aid for the oral thin film, wherein the oral thin film and the application aid are connected to each other in such a way that the user cannot separate the connection without destroying the film, wherein the application aid has a length of 1 cm to 10 cm, a width of 0.5 cm to 5 cm and a thickness of 0.1 mm to 4 mm and the application aid comprises a first region and a second region, wherein the oral thin film is arranged in the first region of the application aid and the second region of the application aid is designed such that a user can touch the application aid in such a way that the oral thin film is not touched.

[0016] Such a connection has the advantage that the user does not need to touch the oral thin film itself to apply it. Contact preferably occurs exclusively via the application aid. Furthermore, in a preferred embodiment, the application aid can be designed to dissolve itself in the user's oral cavity. The firm connection with the application aid makes it particularly advantageous to apply very thin oral thin films, especially those with a thickness of less than 400 µm, or oral thin films equipped with microneedles on their surface.

[0017] In the present description, the term "comprise" should also mean "consisting of".

[0018] The term "application aid" can be understood in the broadest possible sense here.

[0019] According to the invention, the application aid comprises a planar structure with a thickness of 0.1 mm to 4 mm, preferably 0.1 mm to 2 mm or 0.5 mm to 2 mm or 100 µm to 500 µm, on the surface of which the oral thin film is firmly attached.

[0020] The application aid can take on all possible shapes. For example, the application aid can be essentially round, oval, or elliptical.

[0021] The application aid can also be triangular or square, possibly with rounded corners. Furthermore, shapes in other possible polygons, possibly with rounded corners, are possible.

[0022] Mixed forms are also possible, wherein the application aid has, for example, a first round, oval or elliptical area and a second area attached to it, which is, for example, strip-shaped, triangular or square (also polygonal), so that the application aid as a whole has a shape similar to that of a tennis racket, with the second area preferably serving as a "handle" and the first area serving to receive the oral thin film.

[0023] In this context, "firmly bonded" means that the application aid and the oral thin film are so closely connected that the user cannot separate the connection without destroying the film. This bond should remain intact even over extended storage periods.

[0024] The composite according to the invention is characterized in that the application aid comprises a first area and a second area.

[0025] According to the invention, the oral thin film is arranged in the first area of ​​the application aid.

[0026] The second area of ​​the application aid is designed according to the invention in such a way that a user can touch the application aid in such a way that the oral thin film is not touched.

[0027] Preferably, the oral thin film is applied to the first third or half of the surface of the application aid. This leaves two-thirds or the second half of the application aid free, which can then serve as a "handle" for applying the oral thin film.

[0028] The compound according to the invention is preferably characterized in that the application aid has an area that is at least twice as large, preferably 2 to 10 times or 2 to 4 times as large, as the area of ​​the oral thin film.

[0029] In possible embodiments, the application aid has an area of ​​1 cm² to 30 cm², preferably 2 cm² to 15 cm² or 2 cm² to 10 cm².

[0030] In possible embodiments, the oral thin film has an area of ​​0.3 cm² to 10 cm², preferably of 0.5 cm² to 7 cm².

[0031] According to the invention, the application aid has a length of 1 cm to 10 cm, preferably 2 cm to 5 cm.

[0032] According to the invention, the application aid has a width of 0.5 cm to 5 cm, preferably 1 cm to 3 cm.

[0033] In possible embodiments, the oral thin film has a length of 0.5 cm to 5 cm, preferably 1 cm to 4 cm.

[0034] In possible embodiments, the oral thin film has a width of 0.5 cm to 4 cm, preferably 1 cm to 4 cm.

[0035] According to the invention, the application aid has a thickness of 0.1 mm to 4 mm, preferably 0.1 mm to 2 mm or 100 µm to 500 µm.

[0036] In possible embodiments, the oral thin film has a thickness of 0.01 mm to 2 mm, preferably 0.05 mm to 1 mm or 100 µm to 400 µm.

[0037] In possible embodiments, the application aid has a basis weight of 20 g / m² to 800 g / m², preferably of 20 g / m² to 500 g / m².

[0038] In possible embodiments, the oral thin film has a basis weight of 10 g / m² to 600 g / m², preferably of 10 g / m² to 400 g / m².

[0039] The application aid can be single-layered or multi-layered.

[0040] The composite according to the invention is preferably characterized in that the application aid comprises at least one water-soluble polymer.

[0041] Water-soluble polymers encompass chemically very diverse, natural or synthetic polymers whose common characteristic is their solubility in water or aqueous media. A prerequisite is that these polymers possess a sufficient number of hydrophilic groups to ensure water solubility and are not cross-linked. The hydrophilic groups can be non-ionic, anionic, cationic, and / or zwitterionic.

[0042] Water-soluble is preferably understood to mean a solubility of greater than 100 g / L in water at 25°C.

[0043] The at least one water-soluble polymer is preferably selected from the group consisting of starch and starch derivatives, dextrans, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, ethyl or propylcellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, vinylpyrrolidone / vinyl acetate copolymers, polyvinyl alcohols, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatin, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan and / or natural gums, with polyvinyl alcohols being particularly preferred.

[0044] The composite according to the invention is preferably characterized in that the at least one polymer, preferably the water-soluble polymer, is contained in an amount of 10 to 100 wt.% or 10 to 95 wt.%, preferably 60 to 90 wt.%, particularly preferably 80 to 90 wt.%, based on the total weight of the application aid.

[0045] The compound according to the invention is preferably characterized in that the application aid as a whole is water-soluble. Here, "water-soluble" is preferably understood to mean a solubility of greater than 100 g / L in water at 25°C.

[0046] The compound according to the invention is preferably characterized in that the application aid comprises flavorings, flavor masking agents and / or narcotics or local anesthetics.

[0047] Suitable anesthetics or local anesthetics include, for example, aminoamides such as lidocaine, amino esters such as procaine, fomocaine, quinisocaine or cyclonine.

[0048] These are preferably contained in an amount of 0.1 to 10 wt.% or 0.1 to 5 wt.%, based on the total weight of the application aid.

[0049] The compound according to the invention is preferably characterized in that the application aid further comprises at least one auxiliary substance selected from the group consisting of colorants, sweeteners, plasticizers, emulsifiers, enhancers, pH regulators, humectants, preservatives and / or antioxidants.

[0050] Each of these auxiliary materials is preferably contained in an amount of 0.1 to 40 wt.%, preferably 0.1 to 30 wt.%, particularly preferably 0.1 to 15 wt.%, most preferably 0.1 to 10 wt.% or 0.1 to 5 wt.%, based on the total weight of the application aid.

[0051] The stability of the application aid can be adjusted, in particular, by changing the plasticizer content.

[0052] Suitable plasticizers include glycerin.

[0053] The plasticizer(s) is / are preferably contained in an amount of 0.1 to 15 wt.%, most preferably 0.1 to 10 wt.% or 0.1 to 5 wt.%, in particular about 5 wt.%, based on the total weight of the application aid.

[0054] Preferably, the composite according to the invention is characterized in that the application aid is in the form of a film that is as smooth as possible.

[0055] In another embodiment, the composite according to the invention is characterized in that the application aid is in the form of a solidified foam having cavities.

[0056] The cavities and the associated larger surface area of ​​the application aid particularly facilitate the entry of water, saliva or other bodily fluids into the interior of the application aid, thus accelerating the dissolution of the application aid.

[0057] Secondly, the wall thickness of the aforementioned cavities is preferably small, since these, for example, represent solidified bubbles, so that rapid dissolution or destruction of these cavities takes place.

[0058] Another advantage of this embodiment is that, despite the comparatively high basis weight, faster drying can be achieved by manufacturing it as a foam than with a comparable non-foamed composition.

[0059] Preferably, the composite according to the invention is characterized in that the cavities are isolated from each other and preferably have the form of bubbles, wherein the cavities are filled with air or a gas, preferably with an inert gas, particularly preferably with nitrogen, carbon dioxide, helium or a mixture of at least two of these gases.

[0060] According to another embodiment, the cavities are provided to be interconnected, preferably by forming a continuous channel system penetrating the matrix.

[0061] Preferably, the aforementioned cavities have a volume fraction of 5 to 98%, more preferably 50 to 80%, based on the total volume of the application aid. This favorably influences the solution properties of the application aid.

[0062] Furthermore, application aids for foam formation or surfactants can be added to the foam obtained before or after drying to improve the stability of the foam before or after drying.

[0063] Another parameter influencing the properties of the application aid according to the invention is the diameter of the cavities or bubbles. The bubbles or cavities are preferably generated using a foaming machine, with which the diameter of the bubbles can be adjusted within a wide range, almost arbitrarily. Thus, the diameter of the bubbles or cavities can range from 0.01 to 350 µm. A diameter in the range of 10 to 200 µm is particularly preferred.

[0064] Preferably, the compound according to the invention is characterized in that the oral thin film comprises an oral thin film in the form of a film, in the form of a foam and / or in the form of a microneedle system.

[0065] The oral thin film in the composite according to the invention preferably comprises a matrix layer.

[0066] A film is preferably characterized by the fact that it is not in the form of a foam and exhibits no significant irregularities upon optical analysis without aids or magnification. A film can be produced, for example, by spreading and drying a polymer-containing solution, emulsion, suspension, or melt.

[0067] In another embodiment, the oral thin film is characterized in that the matrix layer or the oral thin film is in the form of a solidified foam having cavities.

[0068] The cavities and the associated larger surface area of ​​the films facilitate the entry of water, saliva or other bodily fluids into the interior of the dosage form, thus accelerating the dissolution of the dosage form and the release of the active ingredient.

[0069] Furthermore, with a rapidly absorbed drug, the rapid dissolution can improve transmucosal absorption.

[0070] Secondly, the wall thickness of the aforementioned cavities is preferably small, since these, for example, represent solidified bubbles, so that rapid dissolution or destruction of these cavities takes place.

[0071] Another advantage of this embodiment is that, despite the comparatively high basis weight, faster drying can be achieved by manufacturing it as a foam than with a comparable non-foamed composition.

[0072] Preferably, the oral thin film is characterized in that the cavities are isolated from each other and are preferably in the form of bubbles, wherein the cavities are filled with air or a gas, preferably with an inert gas, particularly preferably with nitrogen, carbon dioxide, helium or a mixture of at least two of these gases.

[0073] According to another embodiment, the cavities are provided to be interconnected, preferably by forming a continuous channel system penetrating the matrix.

[0074] Preferably, the aforementioned cavities have a volume fraction of 5 to 98%, more preferably 50 to 80%, based on the total volume of the matrix layer. This favorably influences the desired effect of accelerating the dissolution of the matrix layer.

[0075] Furthermore, surfactants or surface-active substances can be added to the foaming matrix or the resulting foam before or after drying to improve the stability of the foam before or after drying.

[0076] Another parameter influencing the properties of the dosage form according to the invention is the diameter of the cavities or bubbles. The bubbles or cavities are preferably produced using a foaming machine, with which the diameter of the bubbles can be adjusted within a wide range, almost arbitrarily. Thus, the diameter of the bubbles or cavities can range from 0.01 to 350 µm. A diameter in the range of 10 to 200 µm is particularly preferred.

[0077] A microneedle system, also called a microneedle array, preferably comprises a system containing a large number of microneedles on a carrier.

[0078] The carrier preferably comprises an oral thin film based on at least one polymer. The needles, which preferably have a length of 5 µm to 1000 µm, can be made of different materials, such as ceramic, steel, polymers or SiO₂.

[0079] The microneedle system preferably comprises microneedles with a length of 100 µm to 600 µm, preferably from 250 µm to 350 µm, and particularly preferably from about 300 µm.

[0080] The composite according to the invention is preferably characterized in that the microneedle system is a microneedle system based on glass, SiO2, steel, ceramic, starch and starch derivatives, dextrans, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, ethyl or propylcellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, polyvinyl alcohols, poly(lactide-co-glycoid), hyaluronic acid, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatin, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan and natural gums, wherein this group is not exhaustive.

[0081] The microneedles are preferably attached to the oral thin film using an adhesive layer. A suitable adhesive layer would be, for example, one such as that defined for bonding the application aid to the oral thin film.

[0082] Alternatively, the oral thin film with microneedles can also be produced by using a negative mold of the microneedles during the production of the oral thin film, so that the oral thin film and the microneedles are monolithic.

[0083] Alternatively, the microneedles can be attached to the oral thin film using any suitable fixing materials.

[0084] Preferably, the needles comprise a polymer that is also present in the carrier.

[0085] The composite according to the invention is preferably characterized in that, in the presence of a microneedle system, a raised area is present, particularly adjacent to the microneedles, which is preferably attached to the application aid.

[0086] The raised area is preferably designed in such a way that it protects the microneedles, in particular by making the raised area higher than the microneedles so that the raised area is touched in front of the microneedles.

[0087] The elevation is further preferably characterized in that the enclosed area comprises at least the same area as the microneedle system, particularly preferably the area of ​​the oral thin film, and the height of the elevation corresponds at least to the height of the microneedles.

[0088] This ensures that the microneedles are protected from all sides by the raised area.

[0089] Preferably, said elevation is formed in the form of a continuous molded body and frames a square, rectangular, elliptical or circular base, which is particularly adapted to the arrangement of the microneedle system.

[0090] In another embodiment, the raised area is not a continuous molded body, but partially frames the microneedle system.

[0091] The enhancement is preferably characterized by the fact that the enhancement comprises a water-soluble polymer (as defined above).

[0092] Preferably, the riser comprises the same material as the application aid.

[0093] Regardless of the form of the oral thin film, the oral thin film is preferably characterized in that the oral thin film comprises at least one water-soluble polymer (as defined above).

[0094] The at least one water-soluble polymer is preferably selected from the group consisting of starch and starch derivatives, dextrans, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, ethyl or propylcellulose, polyacrylic acids, polyacrylates, polyvinylpyrrolidones, vinylpyrrolidone / vinyl acetate copolymers, polyvinyl alcohols, polyethylene oxide polymers, polyacrylamides, polyethylene glycols, gelatin, collagen, alginates, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan and / or natural gums, with polyvinyl alcohols being particularly preferred.

[0095] The oral thin film is preferably characterized in that the at least one polymer, preferably the water-soluble polymer, is present in the matrix layer in an amount of 10 to 100 wt.% or 10 to 99 wt.% or 30 to 95 wt.%, preferably 60 to 90 wt.%, particularly preferably 70 to 90 wt.%.

[0096] The compound according to the invention is preferably characterized in that the oral thin film as a whole is water-soluble. Here, "water-soluble" is preferably understood to mean a solubility of greater than 100 g / L in water at 25°C.

[0097] The compound according to the invention is preferably characterized in that the oral thin film comprises at least one pharmaceutically active ingredient.

[0098] The at least one pharmaceutically active ingredient in the oral thin film is preferably selected from the group consisting of hypnotics, sedatives, antieleptics, stimulants, psychoneurotropics, neuroleptics, neuromuscular blockers, antispasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antitussives, expectorants, analgesics, thyroid hormones, sex hormones, glucocorticoid hormones, antidiabetics, antitumor agents, antibiotics, chemotherapeutics, narcotics, anti-Parkinson agents, anti-Alzheimer's agents and / or triptans, this group being non-exhaustive.

[0099] Specific examples include acetaminophen, adrenaline, alprazolam, amlodipine, anastrozole, apomorphine, aripiprazole, atorvastatin, baclofen, benzocaine, benzocaine / menthol, benzydamine, buprenorphine, buprenorphine / naloxone, buprenorphine / naloxone / cetirizine, cetirizine, chlorpheniramine, clomipramine, dexamethasone, dextromethorphan, dextromethorphan / phenylephrine, diclofenac, diphenhydramine, diphenhydramine / phenylephrine, donepezil, dronabinol, epinephrine, escitalopram, famotidine, fentanyl, glimepiride, GLP-1 peptides, granisetron, insulin, insulin nanoparticles, insulin / GLP-1 nanoparticles, ketamine, ketoprofen, ketotifen, and caffeine. Levocetirizine, loperamide, loratadine, meclizine, methylphenidate, midazolam, mirodenafil, montelukast, Multimeric-001, naloxone, nicotine, nitroglycerin, olanzapine, olopatadine, ondansetron, oxybutynin, pectin, pectin / menthol, pectin / ascorbic acid, PediaSUNAT (artesunate and amodiaquine), piroxicam, phenylephrine, prednisolone, pseudoephedrine, risperidone, rivastigmine, rizatriptan,Selegiline, senna glycosides, sildenafil citrate, simethicone, sumatriptan, tadalafil, testosterone, triamcinolone acetonide, triptan, tropicamide, voglibose, zolmitriptan, zolpidem, or pharmaceutically acceptable salts of these compounds.

[0100] The pharmaceutical active ingredient can also be a mixture of different active ingredients.

[0101] The amount of active ingredient in the oral thin film depends on its type and is usually 0.01 to 70 wt.%, preferably 0.1 to 50 wt.%, particularly preferably 1 to 40 wt.%, based on the total weight of the oral thin film.

[0102] It may be advantageous for the oral thin film to also contain at least one excipient selected from the group comprising colourants, flavourings, sweeteners, flavour masking agents, surfactants, enhancers, pH regulators, preservatives, antioxidants and / or plasticizers.

[0103] These excipients are preferably each present in an amount of 0.001 to 20% by weight in the oral thin film.

[0104] The oral thin film is, in principle, not limited in the number of layers it contains.

[0105] Thus, embodiments are conceivable in which the oral thin film comprises further layers. The above definitions apply analogously to these further layers.

[0106] The composite according to the invention is preferably characterized in that the application aid and the oral thin film are connected to each other by means of an adhesive layer, preferably a water-soluble adhesive layer, by means of a seal, preferably a heat seal and / or by means of superimposition.

[0107] An adhesive layer is understood to be a layer that can act as an adhesive, as defined in DIN EN 923:2016-03.

[0108] Water-soluble adhesive layers, such as those described in DE 10 2014 127 452 A1, are particularly suitable as adhesive layers, the content of which is hereby fully incorporated.

[0109] Suitable adhesive layers comprise at least one water-soluble polymer and at least one plasticizer, wherein the at least one water-soluble polymer in the at least one water-soluble adhesive layer comprises shellac, a vinylpyrrolidone / vinyl acetate copolymer, a polyvinylcaprolactam / polyvinyl acetate / polyethylene glycol copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose, and / or polyvinylpyrrolidone, and wherein the at least one plasticizer in the at least one water-soluble adhesive layer comprises glycerin, polyethylene glycol, in particular polyethylene glycol 200, and / or tributyl citrate. The weight ratio of the at least one water-soluble polymer to the at least one plasticizer in the at least one adhesive layer is preferably about 85 to 50 to about 15 to 50.

[0110] Such an adhesive layer, containing at least one water-soluble polymer and at least one plasticizer, can act as an intermediate water-soluble adhesive layer, firmly bonding two further layers that are not sticky in themselves, thus enabling the construction of multilayer composites.

[0111] Sealing refers to any method by which the application aid and the oral thin film can be bonded together. This includes, but is not limited to, bonding by embossing and / or heat sealing.

[0112] Heat sealing refers to the bonding of the application aid and the oral thin film by localized heating and pressure. The localized heating melts the at least one polymer present in the application aid and the oral thin film, respectively, resulting in a solid bond after subsequent cooling. Preferably, the localized heating is performed at a temperature above the melting point or glass transition temperature of the respective polymer.

[0113] Typical temperatures for heat sealing range from about 50°C to 200°C.

[0114] The heat sealing is preferably carried out for about 5 seconds, preferably about 3 seconds and particularly preferably about 2 seconds or less at a temperature of about 50°C to 200°C.

[0115] Overcoating preferably refers to the direct application of a second layer onto an already existing first layer.

[0116] For example, the application aid can be presented, and the composition of the oral thin film in a processable form, such as a solution, emulsion, or suspension, is applied (coated) onto the application aid. After drying, a solid bond is formed. Alternatively, the oral thin film can be presented and coated with the application aid.

[0117] The compound according to the invention is further preferably characterized in that the application aid dissolves in the oral cavity of a patient within 20 s to 5 min, preferably within 30 s to 3 min.

[0118] The compound according to the invention is further preferably characterized in that the application aid and the oral thin film dissolve in the oral cavity of a patient within 20 s to 5 min, preferably within 30 s to 2 min.

[0119] The present invention also relates to a method for producing the composite, preferably as defined above, comprising the steps: Providing an application aid having a length of 1 cm to 10 cm, a width of 0.5 to 5 cm and a thickness of 0.1 mm to 4 mm; providing an oral thin film; and firmly connecting the application aid to the oral thin film, wherein the oral thin film is arranged in the first area of ​​the application aid and the second area of ​​the application aid is designed such that a user can touch the application aid without touching the oral thin film.

[0120] All embodiments defined above for the composite, the oral thin film and the application aid apply analogously to the method according to the invention.

[0121] It is irrelevant whether the application aid or the oral thin film is provided in the first step.

[0122] Preferably, the application aid and / or the oral thin film is provided by a process that involves preparing a solution, emulsion, melt or suspension comprising all the ingredients of the application aid or the oral thin film, followed by spreading and drying the solution, emulsion, melt or suspension.

[0123] All suitable shapes can be cut or stamped from these dried solutions, emulsions, melts or suspensions.

[0124] If microneedles are to be used, they are preferably attached to the oral thin film with an adhesive layer. A suitable adhesive layer here would be, for example, the type defined above for bonding the application aid to the oral thin film.

[0125] Alternatively, the oral thin film with microneedles can also be produced by using a negative mold of the microneedles during the production of the oral thin film, so that the oral thin film and the microneedles are monolithic.

[0126] Alternatively, the microneedles can be attached to the oral thin film using any suitable fixing materials.

[0127] If the application aid and / or the oral thin film is in the form of a foam, the procedure also includes the step of foaming the solution, emulsion, melt or suspension by introducing a gas or gas mixture, by chemical gas generation or by releasing a dissolved gas.

[0128] The firm bonding is preferably achieved by means of a water-soluble adhesive layer, by means of a seal, preferably a heat seal and / or by means of superimposition, as defined above.

[0129] Furthermore, a composite material is described that can be obtained using the procedure described above.

[0130] All embodiments defined above for the composite, the oral thin film and the application aid apply analogously to a composite obtainable by the method described above.

[0131] Furthermore, the present invention relates to a compound, as described above, as a pharmaceutical.

[0132] All embodiments defined above for the composite, the oral thin film and the application aid apply analogously to the medical use according to the invention.

[0133] Description of the characters: Figure 1:

[0134] The Figure 1Figure 1 shows a possible embodiment of the composite, comprising an oral thin film and an application aid for the oral thin film. The composite has a first area of ​​the application aid on which the oral thin film is arranged, and a second area of ​​the application aid which is designed so that a user can touch the application aid without touching the oral thin film.

[0135] An adhesive layer (2) is applied to an application aid (1), onto which the oral thin film (3) is applied in a first area. To prevent the user from having to touch the adhesive layer, a second piece of the application aid (1a) can optionally be applied to the adhesive layer in a second area.

[0136] The oral thin film can optionally be equipped with microneedles (5). These microneedles (5) can either be applied to the oral thin film with a further adhesive layer (4) or attached there by means of alternative fixation methods. Figure 2:

[0137] The Figure 2 Figure 1 shows a further possible embodiment of the system, comprising an oral thin film and an application aid for the oral thin film. The system has a first area of ​​the application aid on which the oral thin film is arranged, and a second area of ​​the application aid which is designed so that a user can touch the application aid without touching the oral thin film. The user is represented here by the stylized hand (9).

[0138] An oral thin film (7) is applied to an application aid (6) in an area that differs from the area the user touches with their hand (9). The oral thin film (7) can optionally be equipped with microneedles (8). Figure 3:

[0139] The Figure 3 Figure 1 shows a cross-section of a possible configuration of the composite, comprising an oral thin film and an application aid for the oral thin film. The composite features a first area of ​​the application aid on which the oral thin film, the microneedles, and a raised area framing the microneedles are arranged to ensure that the microneedles are not damaged.

[0140] An adhesive layer (2) is applied to an application aid (1), onto which the oral thin film (3) is applied in a first area. To prevent the user from having to touch the adhesive layer, a second piece of the application aid (1a) can optionally be applied to the adhesive layer in a second area.

[0141] The oral thin film is equipped with microneedles (5), and a raised area (6) is attached to the application aid (1) that frames the microneedles (5). The microneedles (5) and the raised area (6) can either be applied to the oral thin film with a further adhesive layer (4) or fixed there by means of alternative fixation methods. Figure 4:

[0142] The Figure 4Figure 1 shows a further possible embodiment of the assembly, comprising an oral thin film and an application aid for the oral thin film. The assembly has a first area of ​​the application aid on which the oral thin film, the microneedles, and a raised area framing the microneedles are arranged to ensure that the microneedles are not damaged. The second area of ​​the application aid is designed so that a user can touch the application aid without touching the oral thin film. The user is represented by the stylized hand (9).

[0143] An oral thin film (7) is applied to an application aid (6) in an area that differs from the area touched by the user's hand (9). The oral thin film (7) is equipped with microneedles (8), and a raised area (10) is provided on the application aid (6) that frames the microneedles (8).

[0144] The invention is explained in more detail below using non-limiting examples. Examples

[0145] An oral thin film, in this case a multilayer system with microneedles, was provided with a polyvinyl alcohol foam as an application aid.

[0146] The oral thin film was applied to the application aid using an adhesive layer.

[0147] The application aid has the following formula. material Percentage (dry) Description Polyvinyl alcohol 4-88 84,8 polymer FD&C Red No. 40 0,2 dye Saccharin Na 1,0 sweetener Sucralose 2,0 sweetener Glycerin 5,0 Plasticizers Cherry Aroma 6,0 Flavoring menthol 1,0 Flavoring

[0148] A stable bond is achieved. The very thin oral thin film, which tends to wrinkle, could be applied. Proper application is essential, particularly due to the presence of the microneedles, as improper application can lead to their breakage.

Claims

1. A composite comprising an oral thin film and an application aid for the oral thin film, characterized in that the oral thin film and the application aid are firmly joined to each other, wherein the application aid and the oral thin film are joined to each other in such a way that the user cannot separate the joint without destroying the film, wherein the application aid has a length of 1 cm to 10 cm, a width of 0.5 cm to 5 cm, and a thickness of 0.1 mm to 4 mm, and the application aid comprises a first area and a second area, wherein the oral thin film is disposed in the first area of the application aid, and the second area of the application aid is designed in such a way that a user can touch the application aid in such a way that the oral thin film is not touched.

2. The composite according to any one of the preceding claims, characterized in that the application aid has a surface area which is at least twice as large, preferably 2 to 10 times as large, as the surface area of the oral thin film.

3. The composite according to any one of the preceding claims, characterized in that the application aid has a surface area of 1 cm2 to 30 cm2.

4. The composite according to any one of the preceding claims, characterized in that the application aid comprises at least one water-soluble polymer.

5. The composite according to any one of the preceding claims, characterized in that the application aid as a whole is water-soluble.

6. The composite according to any one of the preceding claims, characterized in that the application aid comprises flavors, flavor masking agents and / or anesthetics.

7. The composite according to any one of the preceding claims, characterized in that the oral thin film comprises an oral thin film in the form of a film, in the form of a foam, and / or in the form of a microneedle system.

8. The composite according to any one of the preceding claims, characterized in that the oral thin film comprises at least one water-soluble polymer.

9. The composite according to any one of the preceding claims, characterized in that the oral thin film comprises at least one active pharmaceutical ingredient.

10. The composite according to any one of the preceding claims, characterized in that the application aid and the oral thin film are joined to each other by means of an adhesive layer, preferably a water-soluble adhesive layer, by means of a seal, preferably a heat seal, and / or are joined to each other by means of coating one on top of the other.

11. The composite according to any one of the preceding claims, characterized in that the application aid dissolves in the oral cavity of a patient within 20 s to 5 min.

12. A method for preparing a composite according to any one of the claims 1 to 11, comprising the steps of: - providing an application aid, having a length of 1 cm to 10 cm, a width of 0.5 cm to 5 cm, and a thickness of 0.1 mm to 4 mm, - providing an oral thin film, and - firmly joining the application aid to the oral thin film, wherein the oral thin film is disposed in the first area of the application aid and the second area of the application aid is designed in such a way that a user can touch the application aid in such a way that the oral thin film is not touched.

13. The method according to claim 12, characterized in that the firm joining is carried out by means of an adhesive layer, preferably a water-soluble adhesive layer, by means of a seal, preferably a heat seal, and / or by means of coating one on top of the other.

14. A composite according to any one of the claims 1 to 11 for use as a medicinal product.