OVERTAPE FOR A TRANSDERMAL DELIVERY SYSTEM

Description

[0001] The present invention relates to an overtape for a transdermal delivery system, wherein the overtape comprises a drug-free adhesive matrix and a backing layer, the drug-free adhesive matrix comprising at least one cross-linked polymer and at least one non-cross-linked polymer, and a transdermal delivery system with the overtape according to the invention. Furthermore, the present invention relates to a method for producing the overtape according to the invention and the transdermal delivery system (TDS) with the overtape according to the invention, as well as their use.

[0002] Overtape is generally understood to be a single-sided adhesive composite material consisting of a backing layer and an adhesive layer. Overtapes are frequently used to aid adhesion of materials that do not adhere sufficiently. An overtape is typically larger than the material to be fixed and is applied so that the adhesive side of the overtape is positioned against and completely encloses the material.

[0003] Due to the aforementioned properties, overtapes are frequently used to fix transdermal drug delivery systems (TDS, syn.Transdermal therapeutic systems (TTS) are used to deliver drugs through a patient's skin into their bloodstream. The use of an overtape is particularly useful for TTS containing a drug-containing matrix that is not adhesive or not sufficiently adhesive, as this ensures secure application of the TTS to the skin and / or prevents premature detachment. Such overtapes can initially be separate from the TTS and only applied to it when the TTS is applied to the skin. However, an overtape can also be applied to the TTS already in place. For the purposes of this application, the term TTS or "transdermal delivery system" is defined as including an overtape.The part of the TDS that includes the active ingredient matrix is ​​referred to in this context as the "TDS core", even though such a TDS core could of course already be used as a TDS without overtape.

[0004] Encasing the material to be fixed with the overtape ensures secure fixation to the user's skin across the entire surface of the TDS. This guarantees good contact between the TDS and the skin, and thus a continuous, controlled release of the active ingredient throughout the entire application period.

[0005] It has been shown that the adhesion of overtapes is often insufficient, particularly under mechanical or thermal stress, or when exposed to sweat and / or moisture. This can cause them to slip on the skin, and in some cases, the drug-containing material they fix can detach completely before the intended treatment duration is reached. This is especially important for transdermal therapeutic systems (TDS) intended for wear over several days, as inadequacies in the adhesive properties of the overtape can alter the contact area of ​​the fixed, drug-containing material, potentially resulting in a lack of therapeutic effect. WO 2003 047 556 describes a transdermal therapeutic system comprising a backing layer, a macroporous diffusion matrix containing at least one pharmaceutical active ingredient, and an adhesive.

[0006] DE 1973 8855 A1 relates to a transdermal therapeutic system comprising a removable protective layer, an adhesive reservoir layer and an optionally adhesive-coated back layer with a unidirectional, preferably longitudinally elastic material with an elasticity of at least 20%.

[0007] WO 2012 / 065740 A1 describes a transdermal delivery system with an active ingredient matrix containing a mixture of a cross-linked polyacrylate and a non-cross-linked polyacrylate.

[0008] It is therefore the object of the present invention to provide an overtape that ensures good fixation of a contact surface. The overtape according to the invention is particularly advantageous for fixing transdermal delivery systems.

[0009] This problem is solved according to the invention by an overtape according to claim 1, which comprises at least one drug-free adhesive matrix and a backing layer, wherein the drug-free adhesive matrix comprises a mixture of at least one cross-linked polymer and at least one non-cross-linked polymer. Furthermore, the problem is solved by a method for producing the overtape according to the invention according to claim 12.

[0010] The present invention therefore relates to an overtape comprising (a) an active ingredient-free adhesive matrix and (b) a backing layer, wherein the drug-free adhesive matrix comprises a mixture of at least one cross-linked polymer and at least one non-cross-linked polymer, wherein the cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers, wherein the non-cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers.

[0011] The overtape according to claim 1 advantageously has good adhesive properties in an area which comes into contact with the skin and is therefore suitable for the permanent fixation of TDS on the skin.

[0012] In its simplest embodiment, an overtape according to the invention comprises at least an active ingredient-free, adhesive matrix and a backing layer arranged thereon, wherein the active ingredient-free adhesive matrix comprises a mixture of at least one cross-linked polymer and at least one non-cross-linked polymer, wherein the cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers, and wherein the non-cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers.

[0013] Optionally, the mixture may also contain a crosslinking agent that is not crosslinked with a polymer.

[0014] The back layer of an overtape according to the invention, arranged on the drug-free adhesive matrix, advantageously consists of a film-like material and / or a fabric or nonwoven.

[0015] Advantageously, the mixture of at least one cross-linked polymer and at least one non-cross-linked polymer is a homogeneous mixture.

[0016] In the present patent application, a polymer is understood to be a homopolymer and / or a heteropolymer consisting of several monomers linearly linked to one another via covalent bonds, wherein a linear main chain may also have branched side chains. While homopolymers have a covalent linkage of identical monomers, heteropolymers (also called copolymers) are composed of different monomers.

[0017] In addition to covalent bonds, (induced) dipole-dipole forces, dispersion forces, and / or hydrogen bonds can also occur in polymers or copolymers, which are collectively referred to as secondary valence bonds. Such secondary valence bonds can contribute to the attractive forces between the polymer chains but are distinct from cross-linking.

[0018] In the present patent application, a polymer is referred to as a cross-linked polymer if it is cross-linked via covalent, ionic, and / or coordinate bonds between at least two monomers of different polymer chains. The cross-linking is usually mediated by so-called functional groups of the monomers, where functional groups are understood to be groups of atoms that are primarily responsible for the reactivity of a molecule. Thus, cross-linked polymers naturally also include polymers in which all functional groups present in a cross-linked polymer participate in the cross-linking process. However, functional groups can also be present in a reactive, unbound form in the cross-linked polymer.

[0019] Accordingly, a polymer is referred to as a non-crosslinked polymer if the polymer is not crosslinked via functional groups, even if it may well have functional groups in reactive, unbound form and secondary valence bonds.

[0020] The overtape according to the invention can be advantageously used for a transdermal dosage system (TDS) and thus contribute to improved adhesion properties of the TDS. Since materials used to produce drug-containing matrices in TDS often exhibit cold-flowing properties and may begin to flow, for example, during storage, encasing the material to be fixed with an overtape has the further advantage of preventing lateral leakage of any active ingredients potentially contained in the material. Particularly when applying TDS containing highly potent active ingredients, this prevents the risk of unintentional contamination of persons or objects coming into contact with the material. Furthermore, it reduces or prevents potential loss of the active ingredient.

[0021] An overtape according to the invention advantageously projects beyond the drug-containing matrix of the TDS on all sides, so that the drug-containing matrix, with its application side (i.e., the side of the TDS generally intended for application to the skin or coming into contact with the skin), is in contact with the user's skin and is enclosed by the overtape on all other sides. This ensures good, continuous drug permeation. As mentioned, the drug-containing matrix of the TDS in the present patent application is also referred to as the TDS core. As explained below, such a TDS core can also include an optional separating layer in addition to the drug-containing matrix.Insofar as an overtape according to the invention and a TDS core (i.e. a conventional transdermal delivery system without overtape) are available separately, the overtape can of course only be applied to the TDS core in the manner described above when it is applied.

[0022] A transdermal delivery system according to the invention therefore comprises at least (a) the overtape according to the invention, (b) a TDS core comprising an active ingredient matrix and optionally a release layer, and (c) optionally a release liner.

[0023] Advantageously, the overtape extends beyond the active ingredient-containing matrix and / or the optional separating layer of the TDS core on all sides.

[0024] The present invention also relates to the medical, veterinary and / or cosmetic use of the Overtape according to the invention, in particular for a transdermal delivery system.

[0025] Furthermore, the present invention relates to a method for producing an overtape according to the invention, wherein the method comprises the following steps: (i) Providing at least one drug-free pressure-sensitive matrix comprising a mixture of at least one cross-linked polymer and one non-cross-linked polymer, (ii) Applying a backing layer to the drug-free pressure-sensitive matrix to obtain an overtape laminate, wherein the cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers, wherein the non-cross-linked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers.

[0026] The term "provision" encompasses both on-site manufacturing and the supply of an active ingredient-free, self-adhesive matrix. This active ingredient-free, self-adhesive matrix may already be covered with a protective film, which can be replaced with an alternative protective film or completely removed in one or more subsequent manufacturing steps.

[0027] In the process according to the invention, an overtape laminate is produced by applying a backing layer to an active ingredient-free, pressure-sensitive matrix. A laminate can be understood to be an active ingredient or a product consisting of two or more layers bonded together over a surface. In the following, the term overtape laminate is used synonymously with overtape.

[0028] Finally, the present invention comprises an overtape, in particular for a transdermal delivery system, which is obtainable according to the method described above.

[0029] In principle, the functional groups contained in the drug-free matrix of the overtape according to the invention can be of different forms. Functional groups of the monomers of a cross-linked or non-cross-linked polymer can, for example, consist of carboxy, hydroxy, allyl, amide, amine, isocyanate, and / or epoxy groups. In a preferred embodiment, however, the functional groups of a cross-linked polymer are selected from carboxy, hydroxy, amide, amine, and / or epoxy groups, in particular from carboxy, hydroxy, and amine groups, and more preferably from carboxy groups. In a further preferred embodiment, a non-cross-linked polymer also comprises functional groups which are selected from carboxy, hydroxy, allyl, amide, amine, isocyanate, and / or epoxy groups, in particular from carboxy, hydroxy, and amine groups, and more preferably from carboxy groups.

[0030] Furthermore, the adhesive properties of the overtape according to the invention can be adjusted by the content of functional groups of the at least one cross-linked or non-cross-linked polymer in the drug-free adhesive matrix. Preferably, the at least one cross-linked polymer has a content of functional groups, in particular carboxyl groups, in the range of about 0.5 to about 50 mol%, preferably about 3 to about 25 mol%, and particularly in the range of about 5 to about 11 mol%.

[0031] In a particularly preferred embodiment, the non-crosslinked polymer also has a carboxyl group content in the range of about 0.5 to about 50 mol%, preferably about 3 to about 25 mol%, and particularly in the range of about 5 to about 11 mol%.

[0032] Cross-linking to produce at least one cross-linked polymer can, in principle, be achieved by heating, aging, or irradiating the polymers with accelerated electrons, ultraviolet and / or gamma radiation, and / or by adding an additive that can react with the introduced functional groups. Preferably, however, cross-linking can be initiated by adding a cross-linking agent, which is preferably added to a non-cross-linked polymer or to the reaction mixture after a polymerization reaction. The addition can also occur during a polymerization reaction.

[0033] In a preferred embodiment, cross-linking is achieved by adding a cross-linking agent, which causes partial or complete cross-linking of the polymer via its functional groups. This cross-linking allows the adhesive properties, such as tackiness, peel strength, tensile strength, and creep resistance, to be influenced and adapted to specific requirements, particularly with regard to the desired treatment duration.

[0034] To produce a cross-linked polymer, the monomers or the polymer are first treated with a cross-linking agent. In a subsequent step, the cross-linked polymer can be mixed with a non-cross-linked polymer.

[0035] Suitable crosslinking agents include di- or multivalent metal ions, which can, for example, form metal carboxylates with carboxyl groups. The metal ions are usually applied in the form of metal chelates, which are soluble in organic solvents. The following compounds can be mentioned as preferred crosslinking agents: diphenyl methane-4-diisocyanate, hexamethylene diisocyanate, titanium acetylacetonate, aluminum acetylacetonate, iron acetylacetonate, zinc acetylacetonate, magnesium acetylacetonate, zirconium acetylacetonate, 2-ethyl-1,3-hexanediol titanate, tetra-isooctyl titanate, tetra-nonyl titanate, polyfunctional propylene imine derivatives, ether derivatives of melamine-formaldehyde resins, highly methylated urethane resins, and imino-melamine resins.

[0036] However, a particularly preferred crosslinking agent is aluminium acetylacetonate and can be purchased, for example, from the company Merck (Germany).

[0037] The crosslinking agent advantageously has a dry weight fraction of less than 2 wt.%, preferably about 1 wt.%, in particular about 0.4 wt.%, of the dry weight fraction of the crosslinked polymer.

[0038] Another way to modify the adhesive properties of the overtape according to the invention is to select the monomers from which the at least one cross-linked or the non-cross-linked polymer is composed. In principle, the resulting polymers can be designed to exhibit specific properties, i.e., favorable solubility for an active ingredient, desired mobility of the active ingredient in the matrix, and a desired transfer rate across the skin. Advantageously, monomers from which the aforementioned polymers can be produced have approximately 2 to approximately 15 carbon atoms, preferably approximately 3 to approximately 13 carbon atoms, and particularly approximately 3 to approximately 11 carbon atoms.

[0039] According to the present invention, the monomers of the cross-linked polymer are selected from the group of acrylates. In the present patent application, a polyacrylate is understood to be a polymer comprising identical or different monomer units, wherein the monomer(s) are advantageously selected from the group consisting of acrylic acid, n-butyl acrylate, isobutyl acrylate, propyl acrylate, methyl acrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, and 2-hydroxyethyl methacrylate.

[0040] In a further preferred embodiment, a polyacrylate polymer can contain one or more monomers which, in addition to the one or more monomers mentioned above, are not selected from the group of acrylates. Advantageously, the dry weight fraction of non-acrylate monomers in the total dry weight of the monomers comprising a cross-linked polymer is a maximum of 52 wt.%. Preferably, however, the fraction of non-acrylate monomers is about 1 to about 50 wt.%, particularly preferably about 5 to about 45 wt.%, and especially about 10 to about 43 wt.%.

[0041] Such non-acrylate monomers are preferably selected from the group consisting of styrene, vinyl acetate, and / or tetramethylsuccinonitrile, preferably from the group consisting of vinyl acetate and tetramethylsuccinonitrile, and particularly from the group consisting of vinyl acetate. In a particularly preferred embodiment, a cross-linked polymer has a dry weight vinyl acetate content of 45% and a dry weight tetramethylsuccinonitrile content of approximately 5% of the total dry weight of the monomers.

[0042] According to the present invention, the non-crosslinked polymer is also selected from the group of polyacrylates, wherein the monomer(s) are selected from the group of acrylic acid, n-butyl acrylate, iso-butyl acrylate, propyl acrylate, methyl acrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate.

[0043] According to a preferred embodiment, the non-crosslinked polymer can also contain non-acrylate monomers. The dry weight fraction of non-acrylate monomers in the total dry weight of the monomers comprising a non-crosslinked polymer is advantageously a maximum of 45 wt.%. However, the fraction of non-acrylate monomers is preferably about 1 to about 40 wt.%, particularly preferably about 5 to about 38 wt.%, and especially about 10 to about 35 wt.%.

[0044] The adhesive properties of the drug-free matrix of the overtape according to the invention can be further modified by the arrangement of the monomers in the at least one cross-linked and the at least one non-cross-linked polymer. Since this arrangement only plays a role with different monomers, copolymers are specifically classified according to the arrangement of their monomers into classes such as statistical, alternating, gradient, graft, or block copolymers. Polymers of an arrangement which, in combination with the respective active ingredient, exhibit suitable properties are preferred, i.e., favorable solubility for the active ingredient, desired mobility of the active ingredient in the matrix, and a desired transfer rate across the skin. Statistical copolymers, also referred to as random copolymers, alternating copolymers, and graft copolymers have proven to be particularly suitable for the overtape according to the invention.

[0045] Preferred cross-linked polyacrylates can be purchased from Henkel (Germany), for example, under the name Durotak 87-2052. Preferred non-cross-linked polyacrylates are available from Henkel (Germany), for example, under the names Durotak 87-2051 and 87-2353.

[0046] The mixing ratio of at least one cross-linked polymer and at least one non-cross-linked polymer can influence the adhesive properties of the drug-free adhesive matrix of an overtape according to the invention.

[0047] It has been shown that a preferred embodiment has a weight ratio of the cross-linked polymer to the non-cross-linked polymer in the dried matrix in a range of approximately 1:4 to approximately 4:1, particularly preferably in a range of approximately 1:2 to approximately 2:1, and more preferably in a range of approximately 1:1.5 to approximately 1.5:1, and more preferably in a range of approximately 1:1. The dividend of the specified ratios determines the weight fraction of the cross-linked polymer to be added to the mixture, and the divisor determines the weight fraction of the non-cross-linked polymer to be added to the mixture.

[0048] Insofar as the drug-free, pressure-sensitive adhesive matrix contains more than one cross-linked and / or more than one non-cross-linked polymer, the ratio of cross-linked polymer to non-cross-linked polymer refers to the dry weight fraction of all cross-linked polymers to the dry weight fraction of all non-cross-linked polymers. This ratio is preferably in the range of approximately 1:4 to approximately 4:1, particularly preferably in the range of approximately 1:2 to approximately 2:1, and especially preferably in the range of approximately 1:1.5 to approximately 1.5:1, and most preferably in the range of approximately 1:1. However, a tape according to the invention preferably comprises only one cross-linked polymer and one non-cross-linked polymer.

[0049] As described above, the overtape according to the invention can advantageously be used for a transdermal delivery system, wherein the TDS comprises a TDS core with an active ingredient-containing matrix. Optionally, the TDS core or the active ingredient-containing matrix can comprise a release liner. Furthermore, the active ingredient-containing matrix of the TDS can be covered by a protective film, a so-called release liner, which is removed before application of the TDS.

[0050] This applies particularly to packaging where the overtape is already applied to the TDS before application. In this case, the TDS, including the TDS core and the overtape, is already a single unit within the packaging and can therefore be applied to the skin as one unit after removal from the packaging.

[0051] The overtape according to the invention can, for example, also be provided as a separate packaging unit, i.e., separate from the TDS core (or a simple, conventional TDS without its own permanently attached overtape), and only be applied to the TDS core or a conventional, simple TDS after or during application of the TDS core to the skin. The overtape according to the invention can also be used independently for various simple, conventional TDS (without an integrated overtape).

[0052] In principle, in all the dosage forms mentioned above, both the overtape itself and the TDS core can have different configurations or shapes. For example, both the overtape and the TDS core can be designed as rectangular, square, round, oval, or similar surfaces. Preferably, a rectangular or square surface has rounded corners. In particular, the overtape or the TDS core can be designed as rectangular, square, or round surfaces, although they can also be designed in different shapes, such as the overtape being round and the TDS core being rectangular.

[0053] To ensure adequate adhesive properties of the TDS and to minimize leakage of the active ingredient from the drug-containing matrix, the overtape, as described above, extends beyond the drug-containing matrix or the TDS core. The area of ​​the overtape extending beyond the drug-containing matrix is ​​advantageously at least 0.5 times, preferably at least 0.7 times, and particularly at least 0.8 times, the area of ​​the drug-containing matrix in contact with the skin.

[0054] As mentioned at the outset, an overtape according to the invention has a backing layer which forms an overtape laminate with the drug-free adhesive layer. Advantageously, this backing layer is designed to be drug-impermeable and thus prevents the drug from leaking out of the TDS when used for a drug-containing TDS, particularly if the TDS core of such a TDS (or a simple, conventional TDS for which the overtape is to be used) has no or a drug-permeable separating layer.

[0055] Suitable materials for such drug-impermeable backing layers include, for example, polymers from the group comprising polyolefins such as polyethylene, polypropylene, or polybutylene; olefin copolymers; polyesters, and of these, in particular polyethylene terephthalates and / or polycarbonates; co-polyesters; polyamides; co-polyamides; polyethylene oxides; polyurethanes; polystyrenes; polyamides; polyimides; polyvinyl acetates; polyvinyl chlorides; polyvinylidene chlorides; copolymers such as acrylonitrile butadiene styrene terpolymers; or ethylene-vinyl acetate copolymers; and the like. A preferred overtape material is selected from a polyolefin and / or a polyester, particularly preferably from a polyolefin foam film or a polyester fabric. A particularly advantageous polyolefin foam film can be obtained, for example, from Sekisui Alveo (Lucerne, Switzerland), and an advantageous polyester fabric can be obtained from Karl Otto Braun.

[0056] It has been shown that the adhesive properties of an overtape can also be influenced by the thickness of the drug-free adhesive layers. Advantageously, the thickness of the dried drug-free adhesive matrix is ​​less than 1 mm, but preferably the thickness is in the range of about 10 µm to about 500 µm, particularly preferably in the range of about 20 µm to about 250 µm, and especially in the range of about 30 µm to about 200 µm, in each case measured in the unstretched state.

[0057] The drug-containing matrix of an advantageous transdermal patch (TDS) can, in principle, be either adhesive or non-adhesive. The drug-containing matrix layer of an advantageous TDS, which is hereinafter also referred to as a patch, can be designed as a solid to semi-solid matrix layer and thus form a drug depot.

[0058] The drug-containing matrix of an advantageous TDS can, in principle, comprise materials known for such matrices. Preferably, however, the drug-containing matrix comprises at least one polymer from the group of polyacrylates, wherein the at least one polyacrylate polymer may further comprise one or more monomers which are not selected from the group of acrylates.

[0059] As explained above, the drug-containing matrix of preferred transdermal delivery systems contains at least one active ingredient. This at least one active ingredient is, without limitation, selected from the classes of analgesics, sympathomimetics, sympatholytics, parasympathomimetics, dopamine agonists, hormones, hormone antagonists, antidepressants, neuroleptics and / or antidementia drugs.

[0060] Useful active ingredients include, but are not limited to, opioid analgesics such as buprenorphine, sufentanil, hydromorphone, morphine, fentanyl, dextropropoxyphene, ethylmorphine, meptazinol, nalbuphine, pethidine, tilidine, butorphanol, dextromoramide, dezocine, ketobemidone, oxymorphone, pentazocine, diacetylmorphine, diamorphine, oxycodone, alfentanil, remifentanil, phenoperidine, anileridine, piritramide, bezitramide, methadone, phenazocine, tapentadol, axomadol, and tramadol; non-opioid analgesics such as epibatidine and scopolamine; oxicams such as meloxicam or piroxicam; 4-aminophenol derivatives such as flupirtine and ketamine; and adrenergic receptor agonists such as clonidine. Naphazoline, tetryzoline, tramazoline, xylometazoline and oxymetazoline, alpha-blockers such as alfuzosin, bunazosin, doxazosin, prazosin, silodosin, tamsulosin, terazosin, trimazosin and dapiprazole, beta-blockers such as bupranolol, timolol, carvedilol, sotalol and nadolol,Parasympathomimetics such as carbachol, pilocarpine, physostigmine, rivastigmine, pyridostigmine, neostigmine, or distigmine; aromatase inhibitors such as anastrozole, letrozole, exemestane, and formestane; dopamine agonists such as cabergoline, terguride, melevodopa, pergolide, lisuride, rotigotine, apomorphine, pramipexole, and ropinirole; corticosteroids such as natural estrogens like estradiol-(17β)-17-butyryl acetate, estradiol 17-β-cipionate, estradiol 13,17-β-dienandate, estradiol 3,17-β-dipropionate, estradiol enanthate, estradiol-3-hydrogen sulfate, estradiol-17-β-(3-phenylpropionate), and estradiol undecylate. Estradiol valerate, estradiol 17-(oxohexonate), epimestrol, quinestrol, quinestradol, ethinyl estradiol, fosferol, estriol, lynestrenol, norethisterone, hydroxyprogesterone, progesterone, norelgestromin, medroxyprogesterone, gestronol, dydrogesterone, chlormadinone, allylestrenol, megestrol and Medrogeston, antidepressants such as clomipramine, amitriptyline, amitriptyline oxide,Opipramol, nortriptyline, fluvoxamine, fluoxetine, citalopram, escitalopram, paroxetine, duloxetine, bupropion, selegiline, rasagiline and ketamine, neuroleptics such as chlorpromazine, fluphenazine, levomepromazine, quetiapine, zotepine, bromperidol, risperidone and aripiprazole, and antidementia drugs such as donepezil, rivastigmine, galantamine and memantine.

[0061] Preferred TDS with an overtape according to the invention, which contain at least one active ingredient, can be used for pain therapy, in the treatment of bronchial asthma, chronic obstructive pulmonary disease (COPD), cardiac arrhythmias, angina pectoris, attention deficit hyperactivity disorder (ADHD), muscle weakness, intestinal obstruction, central anticholinergic syndrome, intestinal and bladder atony, motility disorders, for example of the intestinal tract, dry mouth, nerve gas intoxication, restless legs syndrome, drug addiction, hypertension, tachycardia, heart failure, Alzheimer's disease, dementia, Parkinson's disease, amenorrhea, hyperprolactinemia, as an emetic, for weaning during lactation, erectile dysfunction, diabetes, osteoporosis, hypothyroidism, hyperthyroidism, acromegaly, hormone-dependent tumors, osteoarthritis, rheumatism, hyperandrogenism, hirsutism, for Contraception and therapy for unfulfilled desire to have children, depression, anxiety and panic disorders,It is used to treat sleep disorders, nocturnal enuresis, delusions, hallucinations, and psychotic disorders.

[0062] According to a preferred embodiment, a TDS with an overtape according to the invention contains at least one active ingredient from the class of analgesics, sympathomimetics or aromatase inhibitors, particularly preferably from the class of opioid analgesics and / or aromatase inhibitors, and especially preferably from the class of opioid analgesics.

[0063] In particular, a TDS with an overtape according to the invention is used for the treatment of drug addiction, hypertension, dementia, such as Alzheimer's disease, or pain, especially preferably for the treatment of hypertension and / or pain, particularly preferably for the treatment of pain.

[0064] According to a particularly preferred embodiment, the at least one active ingredient is selected from buprenorphine, fentanyl, clonidine, anastrozole and / or rivastigmine, in particular from buprenorphine, clonidine and / or anastrozole, and in particular preferably from buprenorphine.

[0065] In principle, the active ingredient content in advantageous TDS can vary over a wide range. An advantageous amount of active ingredient, preferably analgesics, sympathomimetics or aromatase inhibitors, particularly preferably sympathomimetics and / or opioid analgesics, especially preferably buprenorphine, is from about 0.3 wt.% to about 50 wt.%, preferably from about 3 wt.% to about 20 wt.%, particularly preferably from about 4.5 wt.% to about 15 wt.%, and particularly from about 7 wt.% to about 12.5 wt.%.

[0066] The at least one active ingredient, in particular clonidine and / or buprenorphine, is preferably present in the form of the free base in the drug-containing matrix.

[0067] When applied, the drug-containing matrix releases at least one active ingredient from the drug-containing matrix into the surrounding tissue, with a significant portion of the active ingredient generally being absorbed systemically.

[0068] The absolute amount of active ingredient contained in the drug-containing matrix typically determines the duration for which a continuous supply of the active ingredient to or into the organism is maintained. Therefore, a high loading of the drug-containing matrix with at least one active ingredient is desirable when the application time of the TDS is long, i.e., several days, preferably three to seven days, and in particular four, five, six, or seven days. In this context, an overtape according to the invention can ensure good fixation of the TDS to the skin, and thus good, continuous drug release, especially during long-term therapy.

[0069] To prevent migration of the active ingredient from the drug-containing core into the drug-free matrix of the overtape, a preferred TDS core (or a preferred conventional TDS intended for use with the overtape) advantageously comprises an optional separating layer arranged between the drug-containing matrix and the overtape. In a particularly preferred embodiment, this separating layer is designed to be drug-impermeable.

[0070] Preferably, films made of, for example, polyester with a thickness of up to 200 µm, preferably from the range of 5 to 150 µm, particularly preferably from the range of 7.5 to 100 µm, especially from the range of 10 to 50 µm, and particularly preferably from the range of 12 to 30 µm, are used as such separating layers. Such separating layers are flexible and can optionally wrap around and cover the edges of the matrix layer, i.e., around the laterally facing side surfaces of the active ingredient-containing matrix.

[0071] Preferably, a separating layer, in particular an active ingredient-impermeable separating layer, is based on a polymer selected from the group consisting of polyolefins, olefin copolymers, polyesters, co-polyesters, polyamides, co-polyamides, polyurethanes, and the like. A separating layer can comprise either one layer or several layers, each of which can consist of the same or different materials. Preferably, however, a separating layer comprises only one layer.

[0072] Examples of suitable materials for a release layer include polyesters, particularly polyethylene terephthalates (PET) and polycarbonates, polyolefins such as polyethylene, polypropylene, or polybutylene, polyethylene oxides, polyurethanes, polystyrenes, polyamides, polyimides, polyvinyl acetates, polyvinyl chlorides, polyvinylidene chlorides, copolymers such as acrylonitrile butadiene styrene terpolymers, or ethylene-vinyl acetate copolymers. A preferred material for a release layer is selected from a polyester, particularly preferably from a polyethylene terephthalate. Such a release layer can be purchased, for example, under the name Hostaphan MN 15 DMF from Mitsubishi Polyester Film GmbH (Germany).

[0073] In one embodiment of a preferred TDS, as mentioned above, the drug-containing matrix or the TDS core and the protruding portion of an overtape according to the invention can be covered on the application side with a removable protective film, also known in technical language as a release liner. During storage of the TDS, this effectively protects the drug-containing matrix or the application layer from mechanical influences and / or unwanted exposure to air. By preventing unwanted exposure to air, degradation of active ingredients contained in the matrix, particularly oxygen-sensitive active ingredients, is prevented, thus improving the storage and long-term stability of the patch. To apply the patch, the protective film is first removed before the system is attached to the skin.To improve grip and thus facilitate removal of the protective film, the protective film on advantageous plasters extends beyond the edge of the overtape.

[0074] Suitable materials for such a release liner include, for example, polyester, polypropylene, polyvinyl chloride, aluminum and paper, wherein at least the side of the release liner that comes into contact with the matrix has a silicone coating, polyethylene coating, fluorosilicone coating or polytetrafluoroethylene coating.

[0075] As mentioned several times, an overtape according to the invention is used in particular for a transdermal delivery system. An advantageous method for producing a TDS with the overtape according to the invention comprises the following steps: (i) Providing at least one drug-containing matrix, (ii) optionally applying a release layer to the at least one drug-containing matrix, (iii) punching out drug-containing TDS cores from the drug-containing matrix and the optional release layer, (iv) applying the overtape according to the present invention to the TDS cores obtained above to obtain an overall laminate, (v) optionally applying the overall laminate obtained above to a release liner, (vi) punching out the overall laminate and the optional release liner to obtain transdermal delivery systems, (vii) optionally packaging the transdermal delivery systems.

[0076] In this process, at least one active ingredient-containing matrix may already be provided with a covering protective film, which can be replaced in one or more manufacturing steps by an alternative protective film or by a release liner.

[0077] In order to achieve the desired shear strength, adhesive strength and release force, it has proven advantageous that a cross-linked polymer used to produce the drug-free adhesive matrix of a preferred overtape according to the invention has a Brookfield viscosity of about 1500 to about 4000 mPas, preferably of about 2000 to about 3000 mPas, and particularly preferably of about 2300 to about 2700 mPas.

[0078] A non-crosslinked polymer used to produce the drug-free adhesive matrix preferably has a Brookfield viscosity of about 2000 to about 6000 mPas, preferably of about 3500 to about 5500 mPas, and particularly preferably of about 4300 to about 5000 mPas.

[0079] Finally, the present invention also relates to a kit comprising an overtape according to the invention and a TDS, which in this case are preferably packaged in separate packaging units such as bags.

[0080] Further features of the invention will become apparent from the following description of exemplary embodiments in conjunction with the claims and the figures. It should be noted that the invention is not limited to the embodiments described above, but is defined by the scope of the accompanying claims. In particular, the individual features may be implemented in different combinations in embodiments according to the invention than in the examples listed below. The following explanation of some exemplary embodiments of the invention refers to the accompanying figures. These show: Figure 1a longitudinal section through a TDS with a first embodiment of an overtape according to the invention, and Figure 2 an exemplary underside view of a TDS with a further embodiment of an overtape according to the invention, showing their relative dimensions.

[0081] In Figure 1A first embodiment of a transdermal delivery system 100 (TDS 100) with an overtape 10 according to the invention is shown. The TDS 100 has a TDS core 3 with an active ingredient-containing layer 4 and a separating layer 5. On the side of the separating layer 5 facing away from the active ingredient-containing layer 4, there is an overtape 10 according to the invention, which comprises a backing layer 1 and an active ingredient-free matrix 2. The overtape 10 extends beyond the TDS core 3 and thus its active ingredient-containing layer 4 on all sides. In the present case, both the overtape 10 and the TDS core 3 of the TDS 100 are designed as rectangular surfaces with rounded corners (not visible in section). In its applied state on the skin of a patient, the drug-free matrix 2 of the overtape 10 is thus located around the drug-containing layer 4 of the TDS core 3.The drug-free matrix 2 of the overtape 10 according to the invention and the drug-containing layer 4 of the TDS core 3 are covered by a release liner 6 for their protection, which is peeled off before use.

[0082] Figure 2 Figure 1 shows a bottom view of a transdermal delivery system 200 with an overtape 20 according to the invention, wherein the overtape 20 itself is round. The TDS core 3 is rectangular with rounded corners. Examples Example 1:

[0083] To produce an overtape according to the invention, a cross-linked polyacrylate (DT 387-2054, Henkel, Germany) is first added to a non-cross-linked polyacrylate (DT 387-2051, Henkel, Germany) in a 1:2 ratio. The mixture is then applied to an intermediate protective film and dried, resulting in a laminate with an active ingredient-free adhesive matrix with a basis weight of less than 60 g / m². Finally, a backing layer of polyolefin foam material with a thickness of approximately 0.4 mm is laminated onto the dried active ingredient-free adhesive matrix to obtain an overtape laminate. Example 2:

[0084] One part buprenorphine is suspended in 2-propanol and mixed with 13 parts of a cross-linked polyacrylate polymer. The resulting mixture is applied to a protective film, dried, and yields a drug-containing matrix with a basis weight of less than 50 g / m². A Hostaphan film MN 15 DMF (Mitsubishi Polyester Film GmbH, Germany) is then laminated onto the dried drug laminate as a release liner. In this example, this drug laminate is die-cut into TDS cores. Subsequently, the intermediate protective film of the overtape laminate is removed (as in Example 1), and the overtape laminate is laminated onto the TDS cores to obtain a complete laminate. TDS are then die-cut from this complete laminate and packaged in pouches.

[0085] Table 1 shows the dimensions and active ingredient content of various exemplary TDS with overtapes according to the invention. Table 1: Dimensions and active ingredient content of TDS with overtapes according to the invention. Buprenorphine TDS 1 Buprenorphine TDS 2 Buprenorphine TDS 3 TDS with overtape [mm] 72x122 72x97 72x72 Active ingredient core [mm] 50x100 50x75 50x50 Active ingredient [mg] 40 30 20 Core area [cm²< ] 50 37,5 25 Overtape area [cm²< ] 87,8 69,8 51,8 Ratio of overtape area to core area 1,8 1,9 2,1 Adhesive area of ​​overtape (overtape minus core) [cm²< ] 37,8 32,3 26,8 Example 3:

[0086] Overtape laminates are produced analogously to Example 1 with a basis weight of the drug-free matrix of < 50 g / m² and are tested with respect to shear strength and adhesive strength. As can be seen from Table 2, the shear strength increases with increasing proportions of the cross-linked polyacrylate (DT 387-2054, Henkel, Germany) (Nos. 1-5). With increasing content of the cross-linking agent aluminum acetylacetonate (AlAcAc) (Merck, Germany), the shear strength increases when applying a constant force of 6 N, while the adhesive strength decreases (Nos. 6-7). Table 2: Shear strength, adhesive strength and release force depending on the different polymer contents. Nr. solids content Shear strength Adhesive strength [N / cm] DT 387-2051 DT 387-2054 AlAcAc n= Changeover time [s] Relative standard deviation [%] Time to elongation up to 2 mm [s] Relative standard deviation [%] 1 80% 20% - 3 73 3,7 39 6,2 0,81 2 70% 30% - 3 138 2,8 73 4,4 1,21 3 60% 40% - 3 356 2,7 176 8,5 0,89 4 55% 45% - 3 419 4,6 230 3,7 0,96 5 50% 50% - 3 694 12,2 447 2,7 0,93 6 100% 0% 0,1% 4 69 10,7 34 12,3 0,95 7 100% 0% 0,2% 6 325 6,5 199 10,6 0,71

Claims

1. An overtape (10, 20) comprising (a) an active-ingredient-free pressure-sensitive adhesive matrix (2) and (b) a backing layer (1), wherein the active-ingredient-free pressure-sensitive adhesive matrix (2) comprises a mixture of at least one crosslinked polymer and at least one non-crosslinked polymer, wherein the crosslinked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers, wherein the non-crosslinked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers.

2. The overtape (10, 20) according to claim 1, wherein the polyacrylate comprises two or more monomer units, wherein the monomers are selected from the group of acrylic acid, vinyl acetate, n-butyl acrylate, iso-butyl acrylate, propyl acrylate, methyl acrylate, tetramethylsuccinonitrile, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxyethyl methacrylate.

3. The overtape (10, 20) according to any one of the preceding claims, wherein the ratio of the weights of a crosslinked polymer to a non-crosslinked polymer in the dried matrix lies in a range of from approximately 1:4 to approximately 4:1, preferably in a range of from approximately 1:2 to approximately 2:1, in particular in a range of from approximately 1:1.5 to approximately 1.5:1, in particular preferably in a range of approximately 1:1.

4. The overtape (10, 20) according to any one of the preceding claims, wherein the backing layer (1) is selected from polyester and / or polyolefin, preferably from a polyolefin foam material.

5. The overtape according to any one of the preceding claims, wherein the layer thickness of the dried active-ingredient-free pressure-sensitive adhesive matrix of the overtape lies in a range of from approximately 10 µm to approximately 500 µm, preferably of from approximately 20 µm to approximately 250 µm, in particular of from approximately 30 µm to approximately 200 µm.

6. A transdermal administration system (100, 200) comprising (a) the overtape (10, 20) according to any one of claims 1 to 5, (b) a TDS core (3) comprising an active-ingredient-containing matrix (4) and optionally a separating layer (5), and (c) optionally a release liner (6), wherein the overtape (10, 20) extends beyond the active-ingredient-containing matrix (4) or the optional separating layer (5) on all sides of the active-ingredient-containing matrix (4).

7. The transdermal administration system (100, 200) according to claim 6, wherein the separating layer (5) is selected from the group of polyesters, preferably from polyethylene terephthalate, polyvinylchloride, polyvinylidene chloride, polyacrylonitrile or copolymers thereof.

8. The transdermal administration system (100, 200) according to claim 6 or 7, wherein the area of the overtape (10, 20) extending beyond the active-ingredient-containing matrix (4) and / or the optional separating layer (5) of the TDS core (3) corresponds to at least 0.5 times, preferably to at least 0.7 times, in particular to at least 0.8 times the area of the active-ingredient-containing matrix (4) resting against the skin and / or of the optional separating layer (5) of the TDS core (3).

9. The transdermal administration system (100, 200) according to any one of claims 6 to 8 for use in medical or veterinary treatment.

10. Use of a transdermal administration system (100, 200) according to any one of claims 6 to 8 for cosmetic application.

11. The transdermal administration system (100, 200) according to any one of claims 6 to 8 for use in pain therapy, in the treatment of hypertension, tachycardia, Alzheimer's disease, dementia, Parkinson's disease or for hormone treatment, preferably for use in pain therapy, wherein the active ingredient is selected from the class of analgesics, sympathomimetics, parasympathomimetics, hormones and / or aromatase inhibitors, preferably from opioids, dopamine agonists, cholinesterase inhibitors, aromatose inhibitors, sexual hormones and / or corticosteroids, in particular from buprenorphine, clonidine, anastrozole, letrozole and / or exemestane, in particular preferably from buprenorphine or clonidine.

12. A method for producing an overtape (10, 20), comprising the steps of (i) providing at least one active-ingredient-free pressure-sensitive adhesive matrix (2) containing a mixture of at least one crosslinked polymer and at least one non-crosslinked polymer, (ii) applying a backing layer (1) to the active-ingredient-free pressure-sensitive adhesive matrix (2) to obtain an overtape laminate, wherein the crosslinked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers, wherein the non-crosslinked polymer is selected from the group of polyacrylates, in particular from the group of acrylate / vinyl acetate copolymers.

13. The method for producing an overtape (10, 20) according to claim 12, wherein the crosslinked polymer used to produce the active-ingredient-free pressure-sensitive adhesive matrix (2) has a Brookfield viscosity of from approximately 1500 to approximately 4000 mPas, preferably of from approximately 2000 to approximately 3000 mPas, in particular preferably of from approximately 2300 to approximately 2700 mPas.

14. The method for producing an overtape (10, 20) according to claim 12 or 13, wherein the non-crosslinked polymer used to produce the active-ingredient-free pressure-sensitive adhesive matrix (2) has a Brookfield viscosity of from approximately 2000 to approximately 6000 mPas, preferably of from approximately 3500 to approximately 5500 mPas, in particular preferably of from approximately 4300 to approximately 5000 mPas.

15. A method for producing a transdermal administration system (100, 200), wherein the method comprises the following steps: (i) providing at least one active-ingredient-containing matrix (4), (ii) optionally applying a separating layer (5) to the at least one active-ingredient-containing matrix (4), (iii) die-cutting active-ingredient-containing TDS cores (3) from the active-ingredient-containing matrix (4) and the optional separating layer (5), (iv) applying an overtape (10, 20) according to any one of claims 1 to 5 to the above obtained active-ingredient-containing TDS cores (3) to obtain an overall laminate, (v) optionally applying the above obtained overall laminate to a release liner (6), (vi) die-cutting the overall laminate and the optional release liner (6) to obtain transdermal administration systems (100, 200), (vii) optionally packaging the transdermal administration systems (100, 200).