Application aids for oral thin films

Abstract

The present invention relates to a composite comprising a first oral film and an application aid for the oral film, wherein the oral film and the application aid are firmly attached to each other, a method for its preparation, and for use as a medicament.

Description

[Technical field]

[0001] The present invention relates to an oral thin film and a complex comprising an application aid for said oral thin film, a method for its preparation and the complex for use as a medicament. [Background technology]

[0002] Oral thin films are usually thin films containing active pharmaceutical ingredients, which are placed directly in the oral cavity or applied to the oral mucosa, where they dissolve. Specifically, these oral thin films are polymer-based thin films containing active ingredients, which release the active ingredients directly into the mucosa when applied to the mucosa, especially the oral mucosa. These oral thin films are generally not sticky on the outside. Good blood circulation in the oral mucosa ensures that the active ingredients are rapidly absorbed into the bloodstream. This administration system has the advantage that the active ingredients are absorbed mostly through the mucosa, thus avoiding the "first-pass metabolism" that occurs in conventional administration forms of active ingredients in tablet form, which are usually taken with a liquid, which can be disadvantageous. The active ingredient is dissolved, emulsified, or dispersed in the membrane. Suitable active ingredients can also be swallowed after the oral thin film dissolves in the mouth, and thus absorbed through the digestive tract.

[0003] Application of oral thin films can be problematic.Due to the shape, size, characteristics and intended application site of oral thin films, and also due to the user's obstacles, difficulties may occur in applying oral thin films to desired sites.Especially for oral thin films with microneedles on one side to increase the active ingredient flux, it is important that these microneedles are not damaged before any application.

[0004] Conventional application aids can ameliorate this problem, but these application aids usually require difficult removal from the oral film and / or have complex structures. There is also a risk that the user may inadvertently swallow the application aid. Summary of the Invention [Problem to be solved by the invention]

[0005] The present application was therefore based on the problem of providing an application aid for oral thin films which overcomes the above mentioned disadvantages. The application aid should have high haptic stability in order to apply the oral thin film to the desired site. Furthermore, the risk of swallowing the application aid should be minimized in general and the risk of the user destroying or damaging the oral thin film before application should be minimized. [Means for solving the problem]

[0006] This problem has surprisingly been solved by a composite according to claim 1, in particular a composite comprising an oral thin film and an application aid for the oral thin film, in which the oral thin film and the application aid are firmly bonded to one another.

[0007] The advantage of such bonding is that the user does not need to touch the oral thin film itself to apply the oral thin film.Preferably, contact is only made via application aid.Furthermore, in a preferred embodiment, application aid is designed to dissolve in the oral cavity of the user.By strong bonding with application aid, very thin oral thin films, especially those having a thickness of less than 400 μm or those with microneedles on one side, can be applied advantageously.

[0008] As used herein, the term "comprising" can also mean "consisting of."

[0009] The term "application aid" is understood herein in the broadest possible sense.

[0010] The application aid preferably comprises a flat structure, to whose surface the oral film is firmly adhered, with a preferred 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.

[0011] The application aid herein can be of any shape, for example, the application aid can be essentially round, oval, or elliptical.

[0012] However, the application aid can also be triangular or rectangular, with rounded corners if desired. Other polygonal shapes, conceivable with rounded corners if desired, are also possible.

[0013] Mixed forms are also possible, such that the application aid has a shape generally resembling that of a tennis racquet, e.g., having a first circular, oval, or elliptical region and a second region, e.g., a strip, triangle, or square (as well as polygon) attached to the first region, the second region preferably functioning herein as a "handle" and the first region functioning to hold the oral film.

[0014] In this case, "strongly bonded" means that the application aid and the oral membrane are bonded to one another such that the user cannot separate the bond without disrupting the membrane. The bond should also remain intact upon storage for longer periods.

[0015] The complex according to the invention is preferably characterised in that the application aid comprises a first region and a second region.

[0016] The oral thin film is preferably disposed in a first region of the application aid.

[0017] The second area of ​​the application aid is preferably designed to allow the user to access the application aid in a manner that does not allow access to the oral film.

[0018] The oral film is preferably adhered to the first third or first half of the face of the application aid, leaving the last two thirds or last half of the application aid free to act as a "handle" for application of the oral film.

[0019] The complex according to the invention is preferably characterized in that the application aid has a surface area at least 2 times greater than the surface area of ​​the oral thin film, preferably 2 to 10 times or 2 to 4 times greater.

[0020] In a possible embodiment, the application aid is 1 cm 2 ~30cm 2 , preferably 2 cm 2 ~15cm 2 , or 2 cm 2 ~10cm 2 has a surface area of

[0021] In a possible embodiment, the oral membrane is 0.3 cm 2 ~10cm 2 , preferably 0.5 cm 2 ~7cm 2 has a surface area of

[0022] In a possible embodiment, the application aid has a length of 1 cm to 10 cm, preferably 2 cm to 5 cm.

[0023] In a possible embodiment, the application aid has a width of 0.5 cm to 5 cm, preferably 1 cm to 3 cm.

[0024] In a possible embodiment, the oral film has a length of 0.5 cm to 5 cm, preferably 1 cm to 4 cm.

[0025] In a possible embodiment, the oral membrane has a width of 0.5 cm to 4 cm, preferably 1 cm to 4 cm.

[0026] In a possible embodiment, 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.

[0027] In a possible embodiment, 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.

[0028] In a possible embodiment, the application aid is 20 g / m 2 ~800g / m 2 , more specifically 20 g / m 2 ~500g / m 2 It has a weight per unit area of

[0029] In a possible embodiment, the oral thin film is 10 g / m 2 ~600g / m 2 , preferably 10 g / m 2 ~400g / m 2 It has a weight per unit area of

[0030] The application aid may be formulated as a single layer or multiple layers.

[0031] The complex according to the invention is preferably characterized in that the application aid comprises at least one water-soluble polymer.

[0032] Water-soluble polymers include natural or synthetic polymers that are chemically quite different, whose common feature is their solubility in water or aqueous media. The prerequisite is that these polymers have a sufficient number of hydrophilic groups for water solubility and are not crosslinked. The hydrophilic groups may be nonionic, anionic, cationic and / or zwitterionic.

[0033] Water soluble is preferably understood to mean a solubility of more than 100 g / L in water at 25°C.

[0034] The at least one water-soluble polymer is preferably selected from the group consisting of starch and starch derivatives, dextran, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, cellulose derivatives such as ethylcellulose or propylcellulose, polyacrylic acid, polyacrylates, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyethylene oxide polymers, polyacrylamide, polyethylene glycol, gelatin, collagen, alginate, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, and / or natural gums, with polyvinyl alcohol being particularly preferred.

[0035] The complex according to the invention is preferably characterized in that at least one polymer, preferably a water-soluble polymer, is present in the matrix layer in an amount of 10 to 100% (w / w), or 10 to 95% (w / w), preferably 60 to 90% (w / w), particularly preferably 80 to 90% (w / w), based on the total weight of the application aid.

[0036] The complex according to the invention is preferably characterized in that the application auxiliaries are generally water-soluble, where water-soluble is also preferably understood to mean a solubility of more than 100 g / L in water at 25° C.

[0037] The complex according to the invention is preferably characterized in that the application aid comprises an aroma, a taste masking agent and / or an anaesthetic or local anaesthetic agent.

[0038] As anesthetics or local anesthetics, aminoamides such as lidocaine, aminoesters such as procaine, homocaine, quinisocaine, or cyclonine are preferred herein.

[0039] These anesthetics or local anesthetics are preferably contained in an amount of 0.1 to 10% (w / w) or 0.1 to 5% (w / w) based on the total weight of the application adjuvant.

[0040] The complex according to the invention is preferably characterized in that the application aid further comprises at least one additive selected from the group comprising colorants, sweeteners, plasticizers, emulsifiers, enhancers, pH regulators, humectants, preservatives and / or antioxidants.

[0041] Each of these additives is preferably present in an amount of 0.1 to 40% (w / w), preferably 0.1 to 30% (w / w), particularly preferably 0.1 to 15% (w / w), most preferably 0.1 to 10% (w / w), or 0.1 to 5% (w / w), respectively, based on the total weight of the application aid.

[0042] Specifically, the stability of the application aid is controlled by the plasticizer content.

[0043] Suitable plasticizers include glycerin.

[0044] The plasticizer is preferably present in an amount of 0.1 to 15% (w / w), most preferably 0.1 to 10% (w / w), or 0.1 to 5% (w / w), especially about 5% (w / w), based on the total weight of the application aid.

[0045] The complex according to the invention is preferably characterized in that the application aid is in the form of a film which is as smooth as possible.

[0046] In another embodiment, the complex according to the invention is characterized in that the application aid is in the form of a solidified foam having cavities.

[0047] The larger cavities and associated surface area of ​​the application aid particularly facilitate the access of water or saliva or other body fluids to the interior of the application aid, thus accelerating dissolution of the application aid.

[0048] On the other hand, since these cavities represent solidified bubbles, it is preferred that the wall thickness of the mentioned cavities is low, so that, for example, these cavities dissolve or collapse quickly.

[0049] A further advantage of this embodiment is that production as a foam results in faster dry times than with comparable non-foamed compositions, despite the relatively high weight per unit area.

[0050] The composite according to the invention is preferably characterized in that the cavities are isolated from one another, preferably in the form of bubbles, and 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.

[0051] According to another embodiment, it is provided that the cavities are interconnected, preferably by forming a connected channel system through the matrix.

[0052] The aforementioned cavities preferably have a volume fraction of 5-98%, preferably 50-80%, relative to the total volume of the application aid, in this way the solution of the application aid is influenced in a favorable manner.

[0053] Additionally, surface active substances or surfactants are added to the application aid for foam formation or to the resulting foam before or after drying to improve the stability of the foam before or after drying.

[0054] Another parameter that influences the properties of the application aid according to the invention is the diameter of the cavities or bubbles. The bubbles or cavities are preferably produced using a foam whipping machine, with which the diameter of the bubbles can be adjusted in a wide range almost at will. The diameter of the bubbles or cavities can therefore range from 0.01 to 350 μm. It is particularly preferred that the diameter is in the range from 10 to 200 μm.

[0055] The complex according to the invention is preferably characterized in that the oral thin film comprises an oral thin film in the form of a membrane, in the form of a foam and / or in the form of a microneedle system.

[0056] The oral thin film in the complex according to the invention preferably comprises a matrix layer.

[0057] The film is preferably characterized in that it is not in the form of a foam and does not show any significant irregularities when analyzed optically without the aid of an aid or magnification. The film is produced, for example, by spreading and drying a polymer-containing solution, a polymer-containing emulsion, a polymer-containing suspension, or a polymer-containing melt.

[0058] In another embodiment, the oral thin film is characterized in that the matrix layer or the oral thin film is present in the form of a solidified foam having cavities.

[0059] The membrane cavities and associated large surface area facilitate the access of water or saliva or other bodily fluids to the interior of the dosage form, thus accelerating dissolution of the dosage form and release of the active ingredient.

[0060] In the case of rapidly absorbed active ingredients, transmucosal absorption is also improved by rapid dissolution.

[0061] On the other hand, since these cavities represent solidified bubbles, it is preferred that the wall thickness of the mentioned cavities is low, so that, for example, these cavities dissolve or collapse quickly.

[0062] A further advantage of this embodiment is that production as a foam results in faster dry times than with comparable non-foamed compositions, despite the relatively high weight per unit area.

[0063] The oral membrane is preferably characterized in that the cavities are isolated from one another, preferably in the form of a bubble, and 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.

[0064] According to another embodiment, it is provided that the cavities are interconnected, preferably by forming a connected channel system through the matrix.

[0065] The aforementioned cavities preferably have a volume fraction of 5-98%, preferably 50-80%, relative to the total volume of the matrix layer, in this way the beneficial effect of accelerating the dissolution of the matrix layer is advantageously influenced.

[0066] Additionally, surface active substances or surfactants may be added to the matrix layer for foam formation or to the resulting foam before or after drying to improve the stability of the foam before or after drying.

[0067] 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 foam whipping machine, with which the diameter of the bubbles can be adjusted in a wide range almost at will. The diameter of the bubbles or cavities can therefore range from 0.01 to 350 μm. It is particularly preferred that the diameter is in the range from 10 to 200 μm.

[0068] Microneedle systems, also known as microneedle arrays, preferably include systems comprising a plurality of microneedles on a support.

[0069] The carrier preferably comprises at least one polymer-based oral membrane. The needle, preferably having a length of 5 μm to 1000 μm, is made of ceramic, steel, polymer or SiO 2 They are manufactured from different materials such as

[0070] The microneedle system preferably comprises microneedles having a length of 100 μm to 600 μm, preferably 250 μm to 350 μm, particularly preferably about 300 μm.

[0071] The composite according to the invention is preferably made of glass, SiO 2、 Preferably, the microneedle systems are characterized by being based on steel, ceramic, starch and starch derivatives, dextran, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, cellulose derivatives such as ethylcellulose or propylcellulose, polyacrylic acid, polyacrylates, polyvinylpyrrolidone, polyvinyl alcohol, poly(lactide-co-glycolide), hyaluronic acid, polyethylene oxide polymers, polyacrylamide, polyethylene glycol, gelatin, collagen, alginate, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, and natural rubber, although this group is not exhaustive.

[0072] The microneedles are preferably attached to the oral membrane by an adhesive layer, for example an adhesive layer as defined for connecting an application aid to the oral membrane is suitable as the adhesive layer.

[0073] Alternatively, oral thin films with microneedles can also be manufactured by using a negative mold of the microneedles during the manufacture of the oral thin film, such that the oral thin film and the microneedles are integral.

[0074] Alternatively, the microneedles are attached to the oral membrane using any suitable attachment means.

[0075] Preferably, the needle comprises a polymer that is also present in the support.

[0076] The composite according to the invention is preferably characterised by the presence of raised areas, preferably adherent to the application aid, where microneedles are present, particularly adjacent to the microneedles.

[0077] The raised areas are preferably designed to protect the microneedles, in particular by being formed higher than the microneedles, so that the raised areas are touched before the microneedles are touched.

[0078] It is further preferred that the raised region is characterized in that the enclosed area includes at least the same area as the microneedle system, particularly preferably the area of ​​the oral thin film, and that the height of the raised region at least corresponds to the height of the microneedles.

[0079] This ensures that the microneedles are protected on all sides by the raised areas.

[0080] The raised area is preferably molded in the form of a continuous body and surrounds a square, rectangular, oval or circular base surface, the raised area being particularly adapted for placement of a microneedle system.

[0081] In another embodiment, the raised region is not a continuous body, but partially surrounds the microneedle system.

[0082] The raised regions are preferably characterized in that they comprise a water soluble polymer (as defined above).

[0083] The raised areas preferably comprise the same material as the application aid.

[0084] Regardless of the form of the oral film, it is preferred that the oral film is characterized in that it comprises at least one water soluble polymer (as defined above).

[0085] The at least one water-soluble polymer is preferably selected from the group consisting of starch and starch derivatives, dextran, carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, sodium carboxymethylcellulose, cellulose derivatives such as ethylcellulose or propylcellulose, polyacrylic acid, polyacrylates, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyethylene oxide polymers, polyacrylamide, polyethylene glycol, gelatin, collagen, alginate, pectin, pullulan, tragacanth, chitosan, alginic acid, arabinogalactan, galactomannan, agar, agarose, carrageenan, and / or natural gums, with polyvinyl alcohol being particularly preferred.

[0086] The oral thin film is preferably characterized in that at least one polymer, preferably a water-soluble polymer, is present in the matrix layer in an amount of 10-100% (w / w), or 10-99% (w / w), or 30-95% (w / w), preferably 60-90% (w / w), particularly preferably 70-90% (w / w), based on the total weight of said matrix layer.

[0087] The complex according to the invention is preferably characterized in that the oral film is totally water-soluble, where water-soluble is also preferably understood to mean a solubility of more than 100 g / L in water at 25° C.

[0088] The conjugate according to the invention is preferably characterized in that the oral film comprises at least one active pharmaceutical ingredient.

[0089] The at least one active pharmaceutical ingredient in the oral thin film is preferably selected from the group consisting of hypnotics, sedatives, antiepileptics, amphetamines, psychoneurotropics, neuroleptics, neuromuscular blocking agents, antispasmodics, antihistamines, antiallergics, cardiac inotropes, antiarrhythmics, diuretics, antihypertensives, vasopressors, antitussives, expectorants, analgesics, thyroid hormones, sex hormones, glucocorticoid hormones, antidiabetics, antineoplastics, antibiotics, chemotherapeutics, narcotics, antiparkinsonian drugs, antialzheimer's drugs, and / or triptans, this group is not exhaustive.

[0090] 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, caffeine, levocetirizine, lopeparidine, Lamido, loratadine, meclizine, methylphenidate, midazolam, mirodenafil, montelukast, multimeric-001, naloxone, nicotine, nitroglycerin, olanzapine, olopatadine, ondansetron, oxybutynin, pectin, pectin / menthol, pectin / ascorbic acid, pediaSUNAT (artesunate and amodialysis) In some embodiments, the active ingredient in the composition is benzodiazepine, benzodiazepine, benzoyl peroxidase ...

[0091] The active pharmaceutical ingredient may also be a mixture of different active ingredients.

[0092] The amount of active ingredient in the oral thin film depends on its type and is usually 0.01-70% (w / w), preferably 0.1-50% (w / w), and particularly preferably 1-40% (w / w), based on the total weight of the oral thin film.

[0093] It may be advantageous for the oral thin film to further contain at least one additive selected from the group comprising colorants, flavorants, sweeteners, taste masking agents, surfactants, enhancers, pH adjusters, preservatives, antioxidants, and / or plasticizers.

[0094] These additives are preferably contained in the oral thin film in an amount of 0.001 to 20% (w / w) each.

[0095] In principle, an oral film is not limited in the number of layers it can contain.

[0096] Thus, embodiments are contemplated in which the oral thin film comprises additional layers, and the above definitions apply analogously to the other layers.

[0097] The complex according to the invention is preferably characterized in that the application aid and the oral film are joined to each other by an adhesive layer, preferably a water-soluble adhesive layer, by sealing, preferably heat sealing, and / or by coating one on top of the other.

[0098] An adhesive layer is understood as a layer which can act as an adhesive, as defined in DIN EN923:2016-03.

[0099] Water-soluble adhesive layers are particularly suitable as adhesive layers, as described in DE 10 2014 127 452 A1, the entire relevant content of which is hereby incorporated herein.

[0100] Suitable adhesive layers include at least one water-soluble polymer and at least one plasticizer, where the at least one water-soluble polymer in the at least one water-soluble adhesive layer includes shellac, vinylpyrrolidone-vinyl acetate copolymer, polyvinylcaprolactam-polyvinyl acetate-polyethylene glycol copolymer, hydroxypropyl cellulose or hydroxypropyl methylcellulose, and / or polyvinylpyrrolidone, and the at least one plasticizer in the at least one water-soluble adhesive layer includes 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 85:50 to about 15:50.

[0101] 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 to firmly bond two further layers that are not themselves tacky to one another, thus making it possible to form a multilayer composite.

[0102] Sealing is understood to mean any possible way in which the application aid and the oral membrane are joined to one another, however, this concludingly does not include joining by embossing and / or heat sealing.

[0103] Heat sealing refers to bonding the application aid and the oral membrane by spot-wise heating and pressure. Spot-wise heating melts at least one polymer present in the application aid or the oral membrane, resulting in a strong bond after recooling. The temperature is preferably raised punctiformly to a temperature above the melting temperature or glass transition temperature of each polymer.

[0104] The usual temperature for heat sealing is about 50°C to 200°C.

[0105] The heat sealing is preferably carried out at a temperature of about 50° C. to 200° C. for about 5 seconds, preferably about 3 seconds, and particularly preferably for about 2 seconds or less.

[0106] Coating in sequence is preferably understood to mean applying a second layer directly onto an existing first layer.

[0107] For example, an application aid is formed and the composition of the oral thin film is applied (coated) to the application aid in a processable form, for example as a solution, emulsion or suspension. Thus, after drying, a strong complex is formed. It is also possible to form an oral thin film and coat the oral thin film with the application aid.

[0108] The complex according to the present invention is further preferably characterized in that the application aid dissolves in the patient's oral cavity within 20 seconds to 5 minutes, preferably within 30 seconds to 3 minutes.

[0109] It is further preferred that the complex according to the invention is characterized in that the application aid and the oral thin film dissolve in the patient's oral cavity within 20 seconds to 5 minutes, preferably within 30 seconds to 2 minutes.

[0110] The present invention also preferably relates to a method for producing a complex as described above, comprising the steps of: - providing an application aid; - providing an oral thin film; - firmly attaching the application aid to the oral membrane; The present invention also relates to a method, comprising:

[0111] All embodiments defined above for the complex, the oral film and the application aid apply analogously to the method according to the invention.

[0112] As used herein, it does not matter whether the application aid or the oral film is prepared in the first step.

[0113] The application aid and / or oral film are preferably prepared by producing a solution, emulsion, dissolution or suspension containing all the components of the application aid or oral film, respectively, followed by spreading and drying the solution, emulsion, dissolution or suspension.

[0114] Any suitable shape may be cut or punched from these dried solutions, emulsions, melts, or suspensions.

[0115] If microneedles are to be present, they are preferably adhered to the oral film by an adhesive layer, for example an adhesive layer as defined above for bonding the application aid to the oral film is suitable as adhesive layer herein.

[0116] Alternatively, oral films having microneedles can also be prepared by using a negative of the microneedles during preparation of the oral film such that the oral film and the microneedles are integral.

[0117] Alternatively, the microneedles are attached to the oral membrane using any suitable attachment means.

[0118] If the application aid and / or oral film is present in the form of a foam, the method also includes the step of foaming the solution, emulsion, dissolution, or suspension by introducing a gas or mixture of gases, by generating a chemical gas, or by expanding a dissolved gas.

[0119] The strong bond is preferably obtained by means of a water-soluble adhesive layer, by sealing, preferably heat sealing, and / or by coating in layers, as defined above.

[0120] The present invention further relates to a complex obtainable by the above method.

[0121] All the embodiments defined above for the complex, the oral film and the application aid apply analogously to the complex obtained by the method described above.

[0122] Furthermore, the present invention also relates to a conjugate as described above or obtainable by the method described above as a medicament.

[0123] All the embodiments defined above for the complex, the oral film and the application aids apply analogously to the medical uses according to the invention. [Brief description of the drawings]

[0124] [Figure 1] 1 shows possible embodiments of an oral thin film and a complex including an application aid for an oral thin film. [Diagram 2] Another possible embodiment of the oral thin film and the complex including an application aid for the oral thin film is shown. [Diagram 3] 1 shows cross-sections of possible embodiments of an oral thin film and a composite including an application aid for an oral thin film. [Figure 4] Another possible embodiment of the oral thin film and the complex including an application aid for the oral thin film is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0125] Description of the drawings: Figure 1: 1 shows a possible embodiment of a composite comprising an oral thin film and an application aid for the oral thin film. The composite has a first region of the application aid where the oral thin film is placed, and a second region of the application aid that is designed to allow the user to touch the application aid without touching the oral thin film.

[0126] An adhesive layer (2) is applied to the application aid (1) and an oral film (3) is applied to a first area thereof. Optionally, pieces of application aid (1a) are reapplied to the adhesive layer in a second area such that the user does not have to touch the adhesive layer.

[0127] The oral film may optionally comprise microneedles (5). These microneedles (5) are applied to the oral film with a separate adhesive layer (4) or are attached to the oral film using alternative adhesive means.

[0128] Figure 2: 2 shows another possible embodiment of a composite comprising an oral thin film and an application aid for the oral thin film, where the composite has a first region of the application aid where the oral thin film is placed, and a second region of the application aid designed to allow the user to touch the application aid such that the oral thin film is not touched. The user is represented by a stylized hand (9).

[0129] The oral film (7) is applied to an area of ​​the application aid (6) that is different from the area that the user will touch with his hand (9). The oral film (7) can optionally be equipped with microneedles (8).

[0130] Figure 3: 3 shows a cross-section of a possible embodiment of a composite including an oral thin film and an application aid for the oral thin film. The composite has a first region of application aid on which the oral thin film, the microneedle, and a raised region surrounding the microneedle are disposed to ensure that the microneedle is not damaged.

[0131] An adhesive layer (2) is applied to the application aid (1) and an oral film (3) is applied to a first area thereof. Optionally, pieces of application aid (1a) are reapplied to the adhesive layer in a second area such that the user does not have to touch the adhesive layer.

[0132] The oral film comprises microneedles (5) and a raised area (6) applied to the application aid (1), the raised area surrounding the microneedles (5). The microneedles (5) and raised area (6) are applied to the oral film with a separate adhesive layer (4) or are adhered to the oral film using an alternative adhesive means.

[0133] Figure 4: Figure 4 shows another possible embodiment of a composite comprising an oral thin film and an application aid for the oral thin film. The composite has a first region of application aid on which the oral thin film, the microneedles, and a raised region surrounding the microneedles are disposed to ensure that the microneedles are not damaged. The second region of application aid is designed to allow the user to touch the application aid without touching the oral thin film. The user is represented by a stylized hand (9).

[0134] The oral film (7) is applied to an area of ​​the application aid (6) that is distinct from the area that the user touches with his hand (9). The oral film (7) comprises microneedles (8) and a raised area (10) is applied to the application aid (6), the raised area surrounding the microneedles (8).

[0135] The invention is explained in more detail below with reference to non-limiting examples. EXAMPLES

[0136] An oral thin film, in this case a multi-layer system with microneedles, was prepared with polyvinyl alcohol foam as an application aid.

[0137] The oral film was applied to the application aid using an adhesive layer.

[0138] The application aid had the following formula:

[0139] [Table 1]

[0140] A stable complex was obtained. A very thin oral film could be applied that was prone to wrinkling. The presence of the microneedles made proper application especially necessary, as improper application would result in the microneedles breaking.

Claims

1. A composite comprising an oral film and an application aid for the oral film, wherein the oral film and the application aid are firmly attached to each other.

2. 2. The composite of claim 1, wherein the application aid comprises a first region and a second region, the oral thin film is disposed in the first region of the application aid, and the second region of the application aid is designed to allow the user to access the application aid without accessing the oral thin film.

3. The complex of claim 1, wherein the application aid has a surface area at least 2 times greater, preferably 2 to 10 times greater, than the surface area of ​​the oral thin film.

4. Application aid: 1 cm ２ ~30cm ２ 2. The composite of claim 1 having a surface area of

5. The complex of claim 1 , wherein the application aid comprises at least one water-soluble polymer.

6. 10. The complex of claim 1, wherein the application aids are generally water-soluble.

7. 10. The complex of claim 1, wherein the application aid comprises a flavoring, a taste masking agent and / or an anesthetic.

8. 10. The conjugate of claim 1, wherein the oral thin film comprises an oral thin film in the form of a membrane, in the form of a foam, and / or in the form of a microneedle system.

9. The conjugate of claim 1 , wherein the oral thin film comprises at least one water soluble polymer.

10. The conjugate of claim 1 , wherein the oral thin film comprises at least one active pharmaceutical ingredient.

11. 2. The composite of claim 1, wherein the application aid and the oral thin film are joined to each other by an adhesive layer, preferably a water-soluble adhesive layer, by sealing, preferably heat sealing, and / or by coating one on top of the other.

12. 10. The complex of claim 1, wherein the application aid dissolves in the patient's mouth within 20 seconds to 5 minutes.

13. A method for producing the composite according to any one of claims 1 to 12, comprising the steps of: - providing an application aid; - providing an oral thin film; - firmly attaching the application aid to the oral membrane; A method comprising:

14. 14. The method according to claim 13, wherein the strong bonding is achieved by means of an adhesive layer, preferably a water-soluble adhesive layer, by sealing, preferably heat sealing, and / or by coating in layers.

15. A conjugate according to any one of claims 1 to 12 for use as a medicament.

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