Improved drug delivery via adhesives

Abstract

Various adhesive compositions comprising one or more active agents, such as pharmaceutical agents, are described. These adhesive compositions exhibit enhanced release characteristics. The incorporation of one or more absorbents in specific proportions and / or in conjunction with certain components improves the release and release characteristics of the active agents. Related methods for enhancing the release of biologically active agents from adhesives, as well as related methods for using the compositions and articles employing them, are also described.

Description

Improved drug delivery via adhesives The present invention relates to an adhesive composition, an article adapted to adhere to biological skin and release at least one active ingredient into the skin, a method for releasing at least one active ingredient into a region of interest on biological skin, and a method for increasing at least one of the (i) degree of release and (ii) release rate of at least one active ingredient from an adhesive composition. The present invention is particularly directed to medicinal adhesives containing one or more pharmaceutical active ingredients, and more particularly, the present invention relates to improving the release and release characteristics of the active ingredients from adhesive compositions. Adhesive compositions that release one or more active agents are known. Although satisfactory in certain respects, some compositions exhibit unpredictable variations in the release rate of the active ingredient(s). Furthermore, some compositions are not biocompatible and should therefore not be left in contact with the skin or biological tissues for an extended period, such as, for example, more than 24 hours. EP 2 110 125 A1 refers to a transdermal patch containing cross-linked PVP as a water-absorbing material in the matrix layer. Therefore, there is a need for improved adhesive compositions that exhibit predictable release characteristics, are biologically compatible, and can be easily adapted and used in a variety of different applications. The present invention addresses the difficulties and drawbacks associated with previously known compositions. In general, the present invention relates to improving the delivery of drugs or active agents, the delivery rate, and / or the delivery characteristics by incorporating one or more absorbents into an adhesive composition. In one aspect, the present invention provides an adhesive composition for use as a medicament, wherein the method of releasing at least one active agent into a region of interest on biological skin comprises: providing an article adapted for placement along biological skin, the article defining at least one face; providing an adhesive composition comprising an adhesive component, from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, a vehicle, and at least one crystallization inhibitor, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass; depositing the adhesive composition onto the face of the article;and apply the article to a region of interest on biological skin, so that the adhesive composition is directed towards and covers the region of interest. As described herein, the incorporation of an absorbent into the adhesive composition containing the active agent results in an improvement in the release and / or release characteristics of the active agent of the composition. In another aspect, the present invention provides an adhesive composition for use as a medicament wherein the degree of release and (ii) rate of release of at least one active agent is increased from an adhesive composition comprising an adhesive component, at least one active agent, a vehicle, and at least one crystallization inhibitor, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass, the method comprising: incorporating at least one absorbent into the adhesive composition, so as to increase the degree and / or rate of release of the at least one active agent.In certain versions of the present invention, the degree of release and / or the release rate of an active agent from a composition that already includes an absorbent can be increased by incorporating additional quantities of absorbent into the composition. In another aspect, the present invention provides an adhesive composition comprising 20% ​​to 90% of an adhesive, 0.1% to 50% of at least one absorbent, 0.1% to 20% of at least one active agent, 0.1% to 30% of at least one soluble crystallization inhibitor, and 0.1% to 30% of a vehicle, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass. As an adhesive, the adhesive composition may comprise from 30% to 80% of a hot melt adhesive, from 0.5% to 45% of at least one absorbent, from 0.5% to 10% of at least one active agent, from 0.5% to 20% of polyvinylpyrrolidone as at least one crystallization inhibitor, and as a vehicle, from 0.5% to 20% of at least one polyhydric alcohol. In another aspect, the present invention provides an article adapted to adhere to biological skin and release at least one active agent onto the skin, the article defining a surface and comprising the adhesive composition of the present invention disposed on at least a portion of the surface. That is, the adhesive composition comprises from 20% to 90% of an adhesive, from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, from 0.1% to 30% of at least one soluble crystallization inhibitor, and from 0.1% to 30% of a vehicle, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass. In the article adapted to adhere to biological skin and release at least one active ingredient into the skin, the adhesive composition may comprise, as an adhesive, 30% to 80% of a hot melt adhesive, 0.5% to 45% of at least one absorbent, 0.5% to 10% of at least one active agent, 0.5% to 20% of polyvinylpyrrolidone as at least one crystallization inhibitor, and as a vehicle, 0.5% to 20% of at least one polyhydric alcohol. The adhesive composition of the present invention can be obtained by a method of forming the adhesive composition that releases at least one active agent. The method comprises providing an adhesive component that includes the adhesive and the vehicle. The method also comprises incorporating from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, and from 0.1% to 30% of polyvinylpyrrolidone as at least one crystallization inhibitor, into the adhesive component, thereby forming the adhesive composition that releases the at least one active agent. Brief description of the drawings Figure 1 is a solubility graph of an active agent as a function of a ratio of two components in compositions according to an embodiment of the present invention. Figure 2 is a flow chart of an active agent of various compositions described in more detail in this document, several of which are in accordance with embodiments of the present invention. Figure 3 is a recovery graph of an active agent from various compositions described in more detail in this document and according to embodiments of the present invention. Figures 4 and 5 are elution graphs of an active agent of various compositions described in more detail in this document and in accordance with embodiments of the present invention. In many applications, it is desirable to incorporate a drug or other active agents into an adhesive matrix to combine the therapeutic effects of the drug or active ingredient(s) with the buffering, moisture-absorbing, and protective properties of the adhesive. The present invention relates to the incorporation of one or more active agents into an adhesive, and particularly into a hydrocolloid adhesive. As described herein, it has been found that incorporating one or more absorbents and / or absorbent agents into an adhesive composition in particular proportions and / or in conjunction with other specified agents improves the release and / or characteristics of one or more active agents, drugs, and / or pharmaceutical products within the adhesive composition. Various aspects of the present invention, regularly referred to herein as "drug-in-adhesive" systems, include, but are not limited to, the following. The active agents are released in a controlled manner from the adhesive composition into a receptor medium, such as adjacent or underlying tissue. The active agents exist in a stable, amorphous, i.e., non-crystalline state within the adhesive composition. Crystallization of the active agents can cause unpredictable variations in the active agent release rate or drug delivery, and such instability must therefore be avoided. The adhesive compositions exhibit good adhesive properties so that they can remain on the skin for an extended period, e.g., 24 hours or more. In general, the present invention provides certain combinations of adhesive, absorbent, drug or active agent, crystallization inhibitor, and vehicle to provide the aforementioned characteristics. The resulting adhesive compositions provide a drug release characteristic without compromising absorption or adhesion performance. A representative example of an active agent is ibuprofen, although the present invention is not limited solely to the use of this active ingredient. Instead, as described in more detail herein, a wide range of active agents or combinations of active agents can be incorporated into the compositions of the present invention. The present invention provides a wide range of adhesive compositions that can be adapted to release one or more active agents in a controlled manner. Table 1 below lists adhesive compositions and their components according to the present invention. All percentages expressed herein are weight percentages unless otherwise stated. Table 1 - Adhesive Compositions continuation Adhesive(s) A wide range of adhesive components can be used in the adhesive compositions according to the present invention. In general, the adhesive or adhesive component can be a hot melt adhesive. In certain aspects, the compositions of the present invention can comprise a pressure-sensitive hot melt adhesive. The adhesive matrix can be based, for example, on polyisobutylene, butyl rubber, polyacrylates, polyurethanes, silicone rubber, natural rubber, SBR rubber, or polyvinyl ether. Thermoplastic elastomers such as styrene-isoprene-styrene block copolymers and styrene-ethylene / propylene-styrene block copolymers can be used, and these may require optional bonding agents and plasticizers. Combinations or blends of elastomers can be more easily employed. Particularly suitable as bases for the pressure-sensitive adhesives of the present invention are rubbers such as linear or radial ABA block copolymers or blends of these ABA block copolymers with simple AB block copolymers. These block copolymers may be based on hydrogenated styrene-butadiene, styrene-isoprene, and styrene-diene copolymers, such as styrene-ethylene-butylene. Styrene-diene copolymers suitable for the practice of the present invention are illustrated by a blend of linear styrene / isoprene / styrene triblock copolymer and linear styrene / isoprene diblock copolymer. Such material is available from Shell Chemical as Kraton D-1161 and has a bonded styrene content of approximately 15% and a diblock content of 17%. A second example is a blend of linear styrene / isoprene / styrene triblock copolymer and linear styrene / isoprene diblock copolymer available from Shell Chemical as Kraton D-1117, which has a bonded styrene content of approximately 17% and a diblock content of 33%. An example of a suitable hydrogenated styrene-diene copolymer is a thermoplastic elastomer comprising a blend of transparent linear triblock and diblock copolymers based on styrene and ethylene / butylene, with a bonded styrene content of 14% by weight. Such a material is commercially available from Shell Chemical Company as Kraton G-1657. Another example is Shell Chemical Company's Kraton G-1652, which is a thermoplastic elastomer composed of a transparent linear triblock copolymer based on styrene and ethylene-butylene, SE / BS, with a bonded styrene content of approximately 30% by weight. Polymers in which there is a combination of chemically saturated and chemically unsaturated blocks are also suitable. For example, a branched copolymer consisting of two polyisoprene chains bonded to the rubber middle block of a styrene / ethylene-butylene / styrene triblock copolymer may be suitable.This material is available from Shell Chemical Company as Kraton Research Product RP6919. It contains 18% styrene, 36% isoprene, and 46% ethylene-butylene by weight. Additionally, a synthetic low-styrene copolymer of styrene-butadiene, commonly referred to as SBR rubber, can be used as a solid rubber. Pressure-sensitive acrylic adhesives are also particularly suitable, illustrated by an acrylic hot melt adhesive manufactured by Schenectedy Chemicals called Durotac 401. Another example is an acrylic solvent adhesive from Aver and Chemicals called Polytex 7600. Absorbent(s) Similarly, a wide range of absorbents can be used in adhesive compositions according to the present invention. Generally, the absorbent includes one or more hydrophilic polymers that are either water-soluble or water-insoluble but swellable, as a moisture-absorbing component. Suitable water-insoluble swellable polymers include crosslinked sodium carboxymethylcellulose, crystalline sodium carboxymethylcellulose, starch-acrylonitrile graft copolymer, and crosslinked dextran. The swellable polymer can also be a material called a "superabsorbent," such as sodium starch polyacrylate. Other hydratable polymers, such as gluten, methyl vinyl ether polymers, and maleic acid and derivatives thereof, can also be included.Suitable water-soluble polymers include sodium carboxymethylcellulose, pectin, gelatin, guar gum, locust bean gum, collagen, tragacanth gum, karaya gum starches, gum arabic, alginic acid, and various sodium and / or calcium salts thereof. Other synthetic absorbents, such as polyvinyl alcohol, polyvinyl acetate, polyvinylpyrrolidone, polyacrylic acid, polyhydroxyalkyl acrylates, polyacrylamides, polyethylene glycols, and high-molecular-weight polypropylene glycols, may also be useful. If the superabsorbent polymer (SAP) is used in adhesive compositions, it comprises a water-swellable, hydrogel-forming absorbent polymer capable of absorbing large quantities of liquids such as water, body fluids (e.g., urine, blood), and the like. Furthermore, the SAP can retain these absorbed fluids under moderate pressure. Typically, the SAP absorbs many times its own weight in water, preferably at least 50 times, more preferably at least 100 times, and most preferably at least 150 times its weight in water. Additionally, the SAP exhibits good absorption of saline fluids under load and a high saline absorption capacity. Typically, the SAP absorbs at least 10 times, preferably at least 30 times, and most preferably at least 50 times its weight in saline fluid. Although the SAP is capable of absorbing many times its own weight in water and / or saline solution, it does not dissolve in these fluids. The ability of PSA to absorb water and / or saline fluid is related to the degree of crosslinking present in the PSA. Increasing the degree of crosslinking increases the overall fluid retention capacity of the PSA under load. The degree of crosslinking is preferably optimized to obtain a composition in which the rate and amount of absorbance are optimized. Preferred PSAs are at least 10%, more preferably from 10% to 50%, and most preferably from 20% to 40% crosslinked. Examples of suitable PSAs include crosslinked and polymerized α,p-ethylenically unsaturated monocarboxylic and dicarboxylic acids and anhydride acid monomers, including, for example, acrylic acid, methacrylic acid, crotonic acid, maleic anhydride / acid, itaconic acid, fumaric acid, and combinations thereof. The superabsorbent polymers useful in the present invention include, e.g., crosslinked acrylate polymers, crosslinked vinyl alcohol-acrylate copolymer products, crosslinked polyvinyl alcohol products grafted with maleic anhydride, crosslinked acrylate-methacrylate copolymer products, crosslinked saponification products of methyl acrylate-vinyl acetate copolymers, crosslinked starch acrylate graft copolymer products, crosslinked saponification products of starch acrylonitrile graft copolymers, crosslinked carboxymethylcellulose polymer products, and crosslinked isobutylene-maleic anhydride copolymer products, and combinations thereof. The superabsorbent polymer(s) is / are normally in particulate form and is / are preferably spherical and has / are an average particle size of 1 micrometer (µm) to 400 µm. Preferably, the particles have an average particle size of 20 µm to 200 µm, and more preferably from 20 µm to 150 µm. In one embodiment, the particle size of the particles is less than 150 µm, or less than 100 µm. Useful, commercially available superabsorbent particles include, e.g., sodium polyacrylate superabsorbent particles available under the AQUA KEEp series of trade names, which include, e.g.Particles having an average particle size of 20 jm to 30 jm available under the trade name Aq Ua KEEP 1 or SH-NF, particles having an average particle size of 200 jm to 300 jm available under the trade name AQUA KEEP 10SH-P, particles having an average particle size of 320 jm to 370 jm available under the trade name AQUA KEEP SA60S, particles having an average particle size of 350 jm to 390 jm available under the trade names AQUA KEEP SA60SX, SA55SX and SA 60SL II, and particles having an average particle size of 250 jm to 350 jm available under the trade name AQUA KEEP SA60N TYPE II from Sumitomo Seika Chemicals Col, Ltd. (Japan). Also available are the super absorbent materials Luquasorb 1010 and Luquasorb 1030 from BASF, Ludwigshafen, Germany. Therefore, in summary, the absorbent(s) used in the adhesive compositions of the present invention is / are normally one or more agents selected from (i) insoluble swellable polymers, (ii) hydratable polymers, (iii) water-soluble polymers, (iv) synthetic absorbents, (v) superabsorbent polymers and / or (vi) combinations of any one or more of (i) - (v). For certain embodiments, it is useful to use one or more types or grades of carboxymethylcellulose (CMC) in the compositions and methods of the present invention. CMC is a cellulose ether composed of repeating cellobiose units. These are composed of two anhydroglucose units (beta-glucopyranose residues). One parameter used to refer to the grades of CMC is the degree of polymerization. This is the number of anhydroglucose units linked by 1,4-glycosidic bonds. Each anhydroglucose unit contains three hydroxyl groups. By substituting the carboxymethyl groups with some of the hydrogens of the hydroxyl groups, sodium carboxymethylcellulose is obtained. The average number of hydroxyl groups substituted per anhydroglucose unit is known as the "degree of substitution." If all three hydroxyl groups are replaced, the maximum theoretical degree of substitution is 3.0 (impossible to achieve in practice). Another parameter used in reference to CMC is the average chain length or degree of polymerization. The average chain length (or degree of polymerization) and the degree of substitution mentioned above determine the molecular weight of the CMC polymer. In many embodiments, the CMC used in the present invention has a degree of substitution of 0.2 to 1.5, and in other embodiments, from 0.7 to 1.2. In particular embodiments, the degree of substitution of the CMC is from 0.65 to 0.90. The molecular weight of the CMC is normally within a range of 17,000 to 700,000. The present invention includes grades of CMC having molecular weights below 17,000 and above 700,000. In certain versions of the present invention, a particularly useful absorbent is commercially available sodium carboxymethylcellulose from various sources, such as Ashland Chemical, under the name AQUASORB A500. It is also contemplated that, instead of, or in addition to, carboxymethylcellulose, hydroxypropyl methylcellulose, and their variants may be used in the present invention. Active agent(s) Additionally, a wide range of active agent(s) may be used in the compositions of the present invention. In general, any active ingredient, active agent, or combination of active ingredients and / or active agents that are biologically active and can be incorporated into the adhesive composition in a stable manner or form may be used. In certain versions of the present invention, the active agent is soluble in the vehicle, and particularly in polyhydric alcohol(s) when used as vehicles in the compositions. In certain versions of the present invention, the active agent forms a complex with the crystallization inhibitor(s), described in more detail herein, which is polyvinylpyrrolidone according to the present invention. The complex is normally the result of a hydrogen bond between the active ingredient(s) and the inhibitor(s). In certain aspects, the active ingredient(s) may be, for example, analgesics or pain relievers such as fentanyl, butyranolol, morphine, buprenorphine, naloxone, codeine, menthol, methyl salicylate, camphor, capsaicin, acetylsalicylic acid; local anesthetics such as lidocaine; anti-acne drugs such as retinoic acid; antianginal drugs such as nitroglycerin, isosorbide dinitrate, nifedipine, nicardipine; antiarrhythmics such as timolol; antibacterials such as amikacin, cephalosporins, macrolides, tetracyclines, quinolones, nitrofurantoin; anticonvulsants such as carbamazepine, phenobarbital, nitrazepam; antidepressants such as tricyclics, bupropion, sertraline, pergolide, fluoxetine; antirheumatic drugs such as diclofenac, ibuprofen, piroxicam, ketoprofen, thiocolchicoside, methotrexate; sex hormones such as progesterone, testosterone, estradiol, levonorgestrel; antifungal drugs such as clotrimazole, ketoconazole, miconazole;Antihypertensives such as sotalol, alprenolol, captopril, enalapril, felodipine, nicardipine, reserpine; anti-hypothyroid drugs such as thyroxine; antimalarials such as artemesin, cinchonidine, primaquine; antimigraine drugs such as ergotamine, sumatriptan, rizatriptan; antiemetic drugs such as domperidone, chlorpromazine, metoclopramide, scopolamine, tetrahydrocannabinoids; skin lighteners such as hydroquinone, hydroquinine; dopamine receptor antagonists such as pergolide, bromocriptine; muscle relaxants such as thiocolchicoside, diazepam; sclerosing agents such as ethanolamine, sodium ricinoleate; vitamins such as A, B, C, E and precursors or various agents such as oxybutynin, finasteride, erythropoietin. Combinations of one or more of these assets are also considered, including combinations of these agents with other principles. Inhibitor(s) of crystallization The present invention utilizes one or more crystallization inhibitors in the compositions. Crystallization inhibitors are used to improve the solubility and stability of the active ingredients in the compositions. They allow for the dissolution of higher concentrations / loads of active agents and, once dissolved, inhibit the subsequent precipitation of the active ingredients out of solution. By employing these strategies, crystallization inhibitors thus increase the availability of the active ingredients for application to human skin during transdermal drug delivery. While not intended to be tied to any particular theory, it is believed that, since more soluble active ingredients are available in the adhesive matrix, crystallization inhibitors indirectly increase the amount of active ingredients delivered to the skin.The high concentrations of active ingredients dissolved in the matrix of transdermal therapeutic systems generally enable a high flow of active ingredients to and through the skin to aid in treatment. Although to improve the availability of solvated actives for treatment, a wide range of crystallization inhibitors can be incorporated, such as, for example, polyvinylpyrrolidone, polyacrylamides, polyvinyl alcohols, polyacrylic acids, caseins, gelatins, polyamines / polyethyleneimines, polyethylene glycols, cellulose, cellulose derivatives, methylcellulose, hydroxypropylcellulose, ethylcellulose, carboxymethylcellulose, non-urethane associated thickeners, quaternary ammonium alginates, xanthan gum, pectin, guar gum, guar gum derivatives, carrageenan, carboxypolymethylene, agar, polyethoxylated sorbitols, butyl methacrylate, butyl methacrylate derivatives, 2-dimethylaminoethyl methacrylate, methyl methacrylate, polyaminoamides, polyaminoimidazolines, polyetherurethanamines, poly(ethylene oxide), acid polyacrylic, silica, silicon dioxide, starch, starch derivatives, dextrin, cyclodextrins, dextran, rosin esters, sterols,Bile acids, polyglucosamines, monoacylglycerols, glycerol monooleate, glycerol monolinoleate, glycerol monopalmitate, glycerol monostearate, glycerol monolaurate, glycerol monocaprylate, glycerol monocaprate, and combinations or mixtures thereof, at least one crystallization inhibitor being polyvinylpyrrolidone (PVP) according to the present invention. In the present invention, the crystallization inhibitor comprises polyvinylpyrrolidone alone or in combination with other crystallization inhibitors. PVP is a white, hygroscopic polymer with a faint, characteristic odor. PVP is usually in powder form, although it can also be in solution, and comprises the N-vinylpyrrolidone monomer as its building block. By selecting suitable polymerization conditions, a wide range of molecular weights can be obtained, extending from low values ​​of a few thousand daltons to approximately 2.2 million daltons, i.e., 2,200 kDa. PVP can be a homopolymer or a copolymer, typically synthesized by free-radical polymerization in water or alcohols with a suitable initiator of vinylpyrrolidone (also known as N-vinylpyrrolidone, N-vinyl-2-pyrrolidone, and N-vinyl-2-pyrrolidinone) as the monomeric unit. PVP polymers include soluble and insoluble homopolymeric PVPs, and copolymers such as vinylpyrrolidone / vinyl acetate and vinylpyrrolidone / dimethylaminoethyl methacrylate. Substantially crosslinked PVP homopolymers are insoluble and are generally known in the pharmaceutical industry as polyvinylpolypyrrolidone, crospovidone, and PVP. The vinylpyrrolidone-vinyl acetate copolymer is generally known in the pharmaceutical industry as copolividon(a), copolividonum, or VP-VAc. The PVP included in the adhesive composition of the present invention is soluble. The term "soluble," when used with reference to PVP, means that the polymer is soluble in water and is generally not substantially crosslinked, and has a weight-average molecular weight of less than 2,200,000. Unlike most polymers, soluble PVP dissolves readily in water and also in a large number of organic solvents, such as alcohols, amines, acids, chlorinated hydrocarbons, amides, and lactams. Soluble PVP polymers have been identified in the pharmaceutical industry by a variety of names, the most commonly used including povidone, povidon(a), polividonum, poly(N-vinyl-2-pyrrolidone), poly(N-vinylbutyrolactam), poly(1-vinyl-2-pyrrolidone), and poly[1-(2-oxo-1-pyrrolidone)ethylene]. PVP homopolymer is generally insoluble in common esters, ethers, hydrocarbons, and ketones.When it dries, the soluble PVP homopolymer is a light flaky powder, which absorbs up to 40% of its weight in water. The amount and type of PVP required in the embodiments of this invention typically depends on the amount and type of drug present in the adhesive composition, as well as the type of adhesive. Typically, PVP is present in an amount of 0.1% to 30% by weight of the total adhesive composition. The soluble PVP for certain versions of the present invention has a weight-average molecular weight of less than 2,200 kilodaltons (kDa), more particularly less than 100 kDa, and more specifically less than 54 kDa. In certain versions, it is useful to use PVP having a weight-average molecular weight of 2,000 to 2,200,000 (i.e., 2 kDa to 2,200 kDa), more particularly 5,000 to 100,000 (i.e., 5 kDa to 100 kDa), and more particularly 7,000 to 54,000 (i.e., 7 kDa to 54 kDa). In certain versions of the present invention, it is useful to use PVP having certain characteristics and / or properties.For example, in certain embodiments, PVP has a weight-average molecular weight (Mw) of 9 to 850 kilodaltons (kDa) and a number-average molecular weight (Mn) of 2 to 200 kDa. In certain aspects, PVP has a glass transition temperature of 110 °C to 180 °C. And, in certain embodiments, PVP has a K-value of 15 to 82. The use of PVP exhibiting all these characteristics is also being considered. As noted, at least one crystallization inhibitor is polyvinylpyrrolidone (PVP). Unlike most polymers, PVP is readily soluble in water and a wide range of organic solvents, including alcohols, amines, acids, chlorinated hydrocarbons, amides, and lactams. The homopolymer is generally insoluble in common esters, ethers, hydrocarbons, and ketones. PVP is typically synthesized by free-radical polymerization of N-vinylpyrrolidone in water or alcohols with a suitable initiator. By selecting appropriate polymerization conditions, a wide range of molecular weights can be obtained, extending from low values ​​of a few thousand daltons to approximately 2.2 million daltons. In certain versions of the present invention, it is advantageous to use one or more commercially available grades of vinylpyrrolidone homopolymers, such as those of the LUVITEC® brand from BASF Corporation. BASF offers a wide range of vinylpyrrolidone homopolymers with different molecular weights (K values) under the name LUViTe C® K. The products are available as powders or aqueous solutions. Table 2 lists characteristic parameters of LUVITEC® K grades. T l 2 - rrrn iv PVP continuation Table 3 shown below presents the usual properties of various grades of PVP commercially available under the trade name LUVITEC. T l - Prihil PVP In certain versions of the present invention, it is useful to employ PVP having specific characteristics and / or properties. For example, in certain embodiments, the PVP has a weight-average molecular weight (Mw) of 9 to 850 kDa and a number-average molecular weight (Mn) of 2 to 200 kDa. In certain aspects, the PVP has a glass transition temperature of 110 °C to 180 °C. And, in certain embodiments, the PVP has a K-value of 15 to 82. The use of PVP exhibiting all of these characteristics is also contemplated. Vehicle(s) Furthermore, a wide range of vehicles, carriers, and / or solvents may be used in the compositions of the present invention. In general, one or more polyhydric alcohols may be used in the compositions of the present invention. Suitable examples of polyhydric alcohols include dihydric alcohols, such as ethylene glycols, polyethylene glycols, propylene glycols, 1,3- and 1,4-butanediols, 1,6-hexanediol, diethylene glycol, bis(hydroxymethyl)cyclohexane, bis(hydroxyethyl)benzene, hydrogenated bisphenol A, hydrogenated bisphenol F, polytetramethylene glycols, polyester diols, and silanol-terminated polysiloxanes; and trihydric alcohols, such as glycerol, trimethylol propane, trimethylol ethane, 1,2,3-butanetriol, 1,2,6-hexanetriol, and polyester triols. and polyhydric alcohols having 4 to 8 or more hydroxyl groups, such as pentaerythritol, diglycerol, α-methylglucoside, sorbitol, xylitol, mannitol, glucose, fructose, sucrose and the like.However, it will be appreciated that the present invention includes the use of other vehicles, carriers and / or solvents instead of, or in addition to, these polyhydric alcohols. Additional aspects In certain embodiments, the adhesive composition is a hydrocolloid adhesive. A basic hydrocolloid adhesive formulation generally comprises a hot-melt adhesive mixed with an absorbent such as sodium carboxymethylcellulose (CMC), gelatin, pectin, alginate, polyacrylate superabsorbent, or the like. Other hydrocarbon resins, such as polyisobutylene, may also be included to adjust the adhesive properties. Any of these formulations may be selected for the base adhesive in a drug delivery application according to the present invention. For effective drug delivery, it is advantageous to incorporate a polyhydric alcohol that acts primarily as a vehicle in which the drug is actually dissolved, but can also have a secondary function as a skin penetration enhancer. Propylene glycol is an example of a polyhydric alcohol that serves both purposes. Other examples of polyhydric alcohol vehicles include glycerol and polyethylene glycols, typically with molecular weights between 200 and 1,000 Da, or any mixture thereof. According to the present invention, polyvinylpyrrolidone is included as a particular crystallization inhibitor to stabilize the drug or the active agent(s). The polyvinylpyrrolidone (PVP) may include soluble, low-molecular-weight PVP homopolymers. The PVP may also increase the viscosity of the polyol phase, in some cases creating a gel, to prevent the polyol phase from migrating and separating from the adhesive matrix. Once mixed, these principles, e.g., certain polyhydric alcohols and certain PVP agents, form a complex multiphase system in which the various components normally form separate domains but nevertheless mix homogeneously into a single cohesive mass. In light of these aspects, the present invention provides a hydrocolloid adhesive formulation as shown below in Table 4. The active agent can be, for example, ibuprofen. miinh iv rrn iv In certain embodiments, the hot melt adhesive includes styrene-isoprene copolymers, the polyhydric alcohol is propylene glycol, the PVP is a soluble homopolymer with a molecular weight of less than 60 kDa, and the absorbent is sodium carboxymethylcellulose (CMC). These mixtures can be combined and extruded at temperatures below 75°C, which is the critical thermal decomposition temperature for many active ingredients such as ibuprofen. This is a unique characteristic that cannot be achieved with solvent-based acrylic adhesives due to the high drying temperatures they typically require. In certain applications, the adhesives can be prepared by incorporating the various components at temperatures ranging from 60°C to 70°C. PVP improves the solubility of certain active ingredients such as ibuprofen in propylene glycol, as shown in Figure 1. In the absence of PVP, the saturation concentration at room temperature is 17.3 wt% ibuprofen in propylene glycol. The solubility of ibuprofen increases to 27.7 wt% when the vehicle is changed to a mixture of 75% propylene glycol and 25% PVP (BASF LUVITEC K17, typical Mw approximately 9,000 Da). The improved solubility allows for an increased dosage of the drug or other active ingredient(s) without risk of crystallization. A mixture of propylene glycol and PVP also improves the release kinetics of ibuprofen, as shown in Figure 2. Compared to a mixture of ibuprofen with hot melt adhesive alone, or compared to a mixture of ibuprofen with hot melt adhesive and absorbent, mixtures incorporating PVP / propylene glycol combinations have release rates approximately 50% higher. Specifically, Figure 2 illustrates the flux of ibuprofen released from various adhesive formulations, measured using Franz diffusion cells employing a silicone rate-limiting membrane and 40% ethanol / saline as the receiving solution. In Figure 2, composition A is 5% ibuprofen in a hot melt adhesive. Composition B is 5% ibuprofen in a hot melt adhesive containing CMC. Composition C is 5% ibuprofen in a hot melt adhesive containing CMC and a 17% PVP mixture in propylene glycol.Furthermore, composition D is 5% ibuprofen in a hot melt adhesive containing CMC and a 43% PVP mixture in propylene glycol. Compositions C and D represent embodiments of the present invention. Formulations containing PVP are more stable in terms of ibuprofen crystallization compared to their non-PVP counterparts. Differential scanning calorimetry of a 5% ibuprofen formulation containing 10% propylene glycol and 34% CMC reveals a thermal transition that does not occur in an equivalent formulation containing PVP. This transition is attributed to the melting of crystals contained in this material, which are not present in the PVP-containing formulations. According to the present invention, the addition of one or more absorbents confers an unexpected advantage beyond simply enabling the formulation to absorb fluid. Drug release is also enhanced by the inclusion of an absorbent material. In certain versions of the present invention, the degree of release of one or more active agents increases more than the increase in the amount of absorbent. For example, in certain embodiments, the degree of release (or the release rate, in certain versions) can be increased by 10% by increasing the amount of absorbent in the adhesive composition by less than 10%, such as, for example, 5%. This aspect can be expressed in terms of multiplication factors.For example, in certain versions of the present invention, by increasing the amount of absorbent in the adhesive composition by a factor of 2.0 (or 200%), the degree of release of an active agent, such as ibuprofen, increases by a factor greater than 2.0 (or greater than 200%). Another particular advantage of the compositions of the present invention is that they can be processed at low temperatures. This is particularly important for a drug such as ibuprofen, which degrades at 75°C. In certain versions of the present invention, the compositions can be processed at 65–70°C. For a solvent-based system, for example, the resulting composition would have to be processed at much higher temperatures to dry it or remove the vehicle or solvent. Similarly, hot melt rubbers would be processed at temperatures of approximately 150°C. In addition to the properties mentioned above, in particular embodiments of the present invention, the adhesive compositions also exhibit a relatively high fluid handling capability. This relatively high fluid handling capability is manifested in one or more of the following ways. In one aspect, the relatively high fluid handling capacity of the adhesive compositions of the present invention is indicated by compositions exhibiting a static absorption of at least 50 g / m² / 24 hours. In certain versions of the present invention, the adhesive compositions exhibit a static absorption of at least 100 g / m² / 24 hours; at least 500 g / m² / 24 hours; at least 1,000 g / m² / 24 hours; at least 2,500 g / m² / 24 hours; and in certain embodiments, at least 5,000 g / m² / 24 hours. In certain versions, the adhesives exhibit a static absorption of 5,000 to 10,000 g / m² / 24 hours. In another aspect, the relatively high fluid handling characteristics of the adhesive compositions are indicated by their moisture vapor transmission rate (MVT). In general, the MVT of the adhesive compositions of the present invention is at least 25 g / m² / 24 hours. In certain embodiments of the present invention, the adhesive compositions exhibit MVT values ​​of at least 50 g / m² / 24 hours; at least 100 g / m² / 24 hours; at least 200 g / m² / 24 hours; at least 350 g / m² / 24 hours; and in certain versions, greater than 500 g / m² / 24 hours. In certain versions, the adhesive compositions exhibit a MVT of 500 to 1000 g / m² / 24 hours. In certain versions of the present invention, the adhesive compositions exhibit a static absorption of at least 500 g / m² / 24 hours and a TTVH value of at least 25 g / m² / 24 hours. A description for determining static absorption and TTVH is provided herein. Methods This document discloses a method for forming an adhesive composition that releases at least one active agent. The method comprises providing an adhesive component that includes an adhesive and a vehicle. The adhesive and the vehicle are described herein. The method also comprises incorporating from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, and from 0.1% to 30% of at least one crystallization inhibitor into the adhesive component to form an adhesive composition that releases the at least one active agent. The absorbent(s), active agent(s), and inhibitor(s) are as described herein. The various components can be incorporated, mixed, and / or otherwise combined using techniques or operations known in the art, such that the various components are homogeneously mixed into a single cohesive mass. The present invention also provides an adhesive composition for use as a medicament in a method of releasing at least one active agent onto a region of interest, such as, for example, biological skin. The method comprises providing an article adapted for placement along biological skin. The article generally defines at least one surface. The method also comprises providing an adhesive composition that includes an adhesive component, from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, a vehicle, and at least one crystallization inhibitor. The method further comprises depositing the adhesive composition onto the surface of the article. Additionally, the method comprises applying the article to a region of interest on biological skin, such that the adhesive composition is directed toward and covers the region of interest.The active agent(s) is / are released from the adhesive composition and transferred to the area of ​​interest, such as a wound or other area of ​​biological skin. The components of the adhesive composition are as described herein. In certain embodiments, the adhesive compositions of the present invention exhibit particular values ​​of polyethylene peel strength and / or particular values ​​of adhesion. The measurement of these properties is described in greater detail herein, along with various evaluations described therein. In certain versions, the adhesive compositions exhibit a polyethylene peel strength of at least 0.197 N / cm (0.5 N / in), more particularly at least 0.591 N / cm (1.5 N / in), and more particularly at least 0.985 N / cm (2.5 N / in). In certain versions, the adhesive compositions exhibit an adhesion value of at least 3.94 N / cm (10 N / in), more particularly at least 9.84 N / cm (25 N / in), and more particularly at least 15.7 N / cm (40 N / in). Medicinal articles The adhesive compositions described herein can be used in conjunction with a wide range of medical articles. Non-limiting examples of such articles include wound dressings, surgical dressings, medical bandages, sports tapes, surgical tapes, sensors, electrodes, ostomy devices or related components such as sealing rings, catheters, connector fittings, catheter connectors, catheter adapters, fluid delivery tubing, electrical wires and cables, negative pressure wound therapy (NPWT) components, surgical drains, wound drainage components, IV line dressings, prostheses, stoma bags, oral patches, transdermal patches, dentures, wigs, bandages, diapers, medical fillers (e.g., liposuction fillers), sanitary pads, corn and callus pads, and blister cushioning and protective pads.Cushioning pads for toes and pads to protect and cushion cannula insertion sites such as tracheostomy cannulas. The medicinal articles include one or more regions or surfaces to which the adhesive compositions of the present invention are applied. The formation of a layer, coating, or other adhesive region on an article allows the article to adhere to a wide range of surfaces, including skin. It is understood that the present invention is not limited to any of these articles. Instead, the present invention includes the use of the adhesive compositions with articles other than those mentioned herein. The medicinal articles may also include one or more layers covering the adhesive layer or coating, such as a release liner. Examples Evaluations were carried out to assess various adhesive compositions according to the present invention. The materials used in the adhesive compositions were as follows. Adhesive: T2650 (Aver and Dennison), styrene-isoprene hot melt adhesive; Absorbent: AQUASORB A500 (Ashland), sodium carboxymethylcellulose; PVP: LUVITEC K17 (BASF), soluble PVP homopolymer with an average molecular weight of 9 kDa; Drug: Ibuprofen (BASF), USP quality (acronym for United States Pharmacopeia); Vehicle: propylene glycol. Three different adhesive formulations were prepared as follows: 5% ibuprofen, 10% propylene glycol, 2% PVP (Formulation 1) 5% ibuprofen, 10% propylene glycol, 5% PVP (Formulation 2) 5% ibuprofen, 10% propylene glycol, 7.5% PVP (Formulation 3) In the first series of tests, 17% absorbent was added (the remainder of the mixture being adhesive), and in the second series, 34% absorbent was added. The samples were immersed in a mixture of ethanol and water for two hours, and solvent samples were then taken to measure the total amount of ibuprofen extracted from the mixture. In all three cases, including the 34% absorbent, more than twice the amount of ibuprofen was recovered, as shown in Figure 3. Specifically, as shown in Figure 3, the ibuprofen recovery for formulations 1 and 3, containing 17% absorbent, was approximately 30% and 26%, respectively; and for the same formulations containing 34% absorbent, the ibuprofen recovery increased to almost 70% and approximately 66%, respectively. These gains were greater than the relative increase in the proportion of absorbent, i.e., from 17% to 34%. Therefore, in certain aspects, the present invention provides methods for increasing the release rate of one or more active ingredients in an adhesive composition by increasing the amount or proportion of absorbent in the composition. In certain versions, increasing the amount of absorbent in the adhesive composition by a factor of 2.0 causes the release rate of ibuprofen to increase by a factor greater than 2.0. Likewise, increasing the amount or proportion of absorbent also increases the rate and degree of ibuprofen release, as detailed in the following evaluation. In another evaluation, the effect of the absorbent on ibuprofen release was investigated. In this evaluation, a series of formulations were prepared using T2560 (hot melt adhesive), AQUASORB A500 (sodium carboxymethylcellulose absorbent), propylene glycol, and various grades of polyvinylpyrrolidone (BASF's LUVITEC K80, LUVITEC K30, and LUVITEC K17). Each formulation included 5% ibuprofen. Ibuprofen elution was measured by immersing a sample or "patch" of adhesive in a mixture of 40% ethanol in saline solution (0.8% NaCl in water) and sampling the liquid phase after 2 hours and again after 6 hours. The ibuprofen concentration in the solution was measured by HPLC (high-performance liquid chromatography), and this value was used to calculate the ibuprofen released from the patch as a percentage of the total ibuprofen contained in the patch. Table 5 below lists the formulations and results. A main effects analysis was performed using the statistical software MINITAB® from Minitab Inc., which revealed that higher amounts of A500 led to greater ibuprofen release.With reference to Figures 4 and 5, on average, doubling the amount of A500 from 17% to 34% led to a substantial increase in ibuprofen elution after 2 and 6 hours of immersion time. In another assessment, several compositions were prepared. For each composition, a comparative composition was prepared. For each set of resulting compositions, the following measurements were performed: (i) adhesion to polyethylene, i.e., "Detachment", (ii) Adhesion, (iii) release of active ingredient after 2 hours, i.e., "Elution at 2 h", (iv) release of active ingredient after 6 hours, i.e., "Elution at 6 h", and (v) fluid handling capacity, i.e., "CMF". Specifically, the samples were prepared and evaluated as follows. Sample preparation The adhesive components were mixed in a sigma paddle mixer heated to approximately 70 °C. After mixing, all adhesive samples were pressed into sheets approximately 0.8 mm thick and laminated on one side with a 70-micron thick adhesive-coated polyurethane film. Landslide Samples measuring one inch wide by approximately five inches long were applied to the surface of a polyethylene film using a 2.04 kg (4.5 lb) roller and allowed to stand for approximately one minute before peeling off at a ninety-degree angle and at a speed of 30.5 cm / minute (12 inches / minute) using a pull tester to record the average force required for removal. Adherence The samples were mounted on a support with the adhesive side facing up. A loop was formed from a 0.127 mm (5 mil) piece of polyester film measuring 15 cm long by 2.54 cm wide and placed in contact with the adhesive surface, forming a contact area of ​​2.54 cm (1 in) x 2.54 cm (1 in). The polyester loop was then separated from the adhesive. A pull tester was used to bring the loop into contact with and separate it from the adhesive at a crosshead speed of 30.5 cm / min (12 in / min), and the maximum force measured during removal was taken as a quantitative measurement of adhesion. Elution A disc measuring 1.91 cm (0.75 in) in diameter was cut from each sample and placed in a vial containing approximately 20 mL of an ethanol-saline solution (40% by volume ethanol in a 0.9% by weight sodium chloride solution in water). The vial was inverted at room temperature, and samples of the solution were taken for analysis after two and six hours. The concentration of ibuprofen in the solution was quantified using ultraviolet absorbance, allowing the percentage of ibuprofen release to be calculated as a weight percentage of the total amount present in the sample. Fluid handling capability Fluid handling ability is a measure of the compound's combined capacity to absorb moisture and evaporate it into the environment. This test is performed by laminating a sample cut to the size of a Paddington cup onto the cup, rubber-ring side down. The circular sealing ring is placed on the sample inside the cup, and the screws are secured. The cup is weighed (W1). The cup is then inverted and filled with 20 mL of a saline solution (0.9 wt. NaCl and 0.04 wt. CaCl2 in deionized water). The metal sealing plate is secured to the top of the cup. The filled cup is weighed (W2). The cup is placed sample-side down in an oven at 37°C for 24 hours. After 24 hours, the cup is removed from the oven and allowed to cool to room temperature for 30 minutes. The cup is then weighed (W3). The metal sealing plate is removed, and the cup is emptied.The cup is left to stand for 15 minutes on a cloth to remove the saline solution and is then weighed (W4). The test conditions are 23 °C (±2 °C) and 50% (±2%) relative humidity. The samples tested herein had a thickness of 0.8 mm. The moisture vapor transmission rate (MVT) is equal to (W2-W3) x1000. The static absorption is equal to (W4-W1) x1000. The fluid handling capacity (FHC) in g / 10 cm² / 24 hours is determined as follows: CMF= (W2-W3) + (W4-W1) Tables 6, 8, 10, and 12 present the comparative composition AD, respectively, without absorbent. These tables also present compositions according to the present invention that include an absorbent, namely Compositions 1 and 3. Compositions 2 and 4 are not according to the present invention, without polyvinylpyrrolidone. Tables 7, 9, 11, and 13 present the test results for evaluating release, adhesion, elution, and fluid handling capabilities. Table 6 - Formulations - Table 8 - Formulations T l - R llr Table 1.- Formulations T l 1.- R llr Table 1.- Formulations - As shown in Tables 6-13, the incorporation of an absorbent into an adhesive formulation significantly increases the elution of ibuprofen (both after 2 hours and after 6 hours). Specifically, as shown in Tables 6 and 7, the incorporation of an absorbent into an adhesive composition results in an increase in elution at 2 hours from 12% to 20% and an increase in elution at 6 hours from 23% to 35%. As shown in Tables 8 and 9, the incorporation of an absorbent into an adhesive composition results in an increase in elution at 2 hours from 15% to 22% and an increase in elution at 6 hours from 28% to 44%. As shown in Tables 10 and 11, the incorporation of absorbent into an adhesive composition produces an increase in elution at 2 hours from 9% to 16% and an increase in elution at 6 hours from 19% to 31%.Furthermore, as shown in Tables 12 and 13, the incorporation of absorbent into an adhesive composition produces an increase in elution at 2 hours from 15% to 25% and an increase in elution at 6 hours from 28% to 52%.

Claims

1. An adhesive composition comprising: from 20% to 90% of an adhesive; from 0.1% to 50% of at least one absorbent; from 0.1% to 20% of at least one active agent; from 0.1% to 30% of at least one soluble crystallization inhibitor; and from 0.1% to 30% of a vehicle, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass.

2. The adhesive composition of claim 1, wherein the adhesive is a hot melt adhesive, preferably wherein the concentration of the hot melt adhesive is from 30% to 80%. 3.The adhesive composition of claim 1, wherein the at least one absorbent is selected from the group consisting of (i) insoluble swellable polymers, (ii) hydratable polymers, (iii) water-soluble polymers, (iv) synthetic absorbents, (v) superabsorbent polymers, and (vi) combinations of any one or more of (i) - (v).

4. The adhesive composition of claim 1, wherein the at least one absorbent is carboxymethylcellulose.

5. The adhesive composition of claim 1, wherein the concentration of at least one absorbent is from 0.5% to 45%. 6.The adhesive composition of claim 1, wherein the at least one active agent is selected from the group consisting of analgesics, local anesthetics, antiacne agents, antianginal agents, antiarrhythmics, antibacterials, anticonvulsants, antidepressants, antirheumatics, sex hormones, antifungals, antihypertensives, antihypothyroid agents, antimalarials, antimigraine agents, antiemetics, skin bleaching agents, dopamine receptor antagonists, muscle relaxants, sclerosing agents, vitamins, and combinations thereof, preferably wherein the concentration of the at least one active agent is from 0.5% to 10%.

7. The adhesive composition of claim 1, wherein the concentration of polyvinylpyrrolidone is from 0.5% to 20%. 8.The adhesive composition of claim 1, wherein the vehicle includes a polyhydric alcohol, preferably wherein the polyhydric alcohol is selected from the group consisting of propylene glycols, glycerols, polyethylene glycols, and combinations thereof, preferably wherein the concentration of the polyhydric alcohol is from 0.5% to 20%.

9. The adhesive composition of claim 1, wherein the adhesive composition exhibits a peel strength on polyethylene of at least 0.197 N / cm (0.5 N / in), preferably at least 0.591 N / cm (1.5 N / in).

10. The adhesive composition of claim 1, wherein the adhesive composition exhibits a static absorption of at least 50 g / m² / 24 hours.

11. An article adapted to adhere to biological skin and release at least one active agent onto the skin, the article defining a surface and comprising the adhesive composition of claim 1 disposed on at least a portion of the surface.12.An adhesive composition for use as a medicament, wherein the method of releasing at least one active agent into a region of interest on biological skin comprises: providing an article adapted for placement along biological skin, the article defining at least one face; providing an adhesive composition including an adhesive component, from 0.1% to 50% of at least one absorbent, from 0.1% to 20% of at least one active agent, a vehicle, and at least one crystallization inhibitor, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass; depositing the adhesive composition onto the face of the article; and applying the article to a region of interest on biological skin, such that the adhesive composition is directed toward and covers the region of interest.

13. The composition for use according to claim 12, wherein the adhesive composition is placed in contact with at least a portion of the region of interest on biological skin.

14. The composition for use according to claim 12, wherein the at least one absorbent is selected from the group consisting of (i) insoluble swellable polymers, (ii) hydratable polymers, (iii) water-soluble polymers, (iv) synthetic absorbents, (v) superabsorbent polymers, and (vi) combinations of any one or more of (i)–(v).

15. The composition for use according to claim 12, wherein the at least one absorbent is carboxymethylcellulose. 16.The composition for use according to claim 12, wherein the at least one active agent is selected from the group consisting of analgesics, local anesthetics, antiacne agents, antianginal agents, antiarrhythmics, antibacterials, anticonvulsants, antidepressants, antirheumatics, sex hormones, antifungals, antihypertensives, antihypothyroid agents, antimalarials, antimigraine agents, antiemetics, skin bleaching agents, dopamine receptor antagonists, muscle relaxants, sclerosing agents, vitamins, and combinations thereof.

17. The composition for use according to claim 12, wherein the at least one active agent is an antirheumatic, preferably ibuprofen. 18.The composition for use according to claim 12, wherein the vehicle is a polyhydric alcohol, preferably wherein the polyhydric alcohol is selected from the group consisting of propylene glycol, glycerol, polyethylene glycol, and combinations thereof, preferably wherein the polyhydric alcohol is propylene glycol.

19. The composition for use according to claim 12, wherein polyvinylpyrrolidone is present in the adhesive composition at a concentration of 0.1% to 30%.

20. The composition for use according to claim 12, wherein the adhesive composition exhibits a peel strength on polyethylene of at least 0.197 N / cm (0.5 N / in), preferably at least 0.591 N / cm (1.5 N / in).

21. The composition for use according to claim 12, wherein the adhesive composition exhibits a static absorption of at least 50 g / m² / 24 hours. 22.An adhesive composition for use as a medicament, wherein increasing at least one of the (i) degree of release and (ii) rate of release of at least one active agent of the adhesive composition, which includes an adhesive component, at least one active agent, a vehicle, and at least one crystallization inhibitor, wherein the at least one active agent exists in an amorphous, stable state within the adhesive composition, the at least one crystallization inhibitor is polyvinylpyrrolidone, and the various components are homogeneously mixed into a single cohesive mass, the method comprising: incorporating at least one absorbent into the adhesive composition, so as to increase the degree and / or rate of release of the at least one active agent.

23. The composition for use according to claim 22, wherein at least one active agent is ibuprofen. 24.The composition for use according to claim 23, wherein increasing the amount of absorbent in the adhesive composition by a factor of 2.0 increases the degree of ibuprofen release by a factor greater than 2.

0.

25. The composition for use according to claim 22, wherein polyvinylpyrrolidone is present in the adhesive composition at a concentration of 0.1% to 30%.

26. The composition for use according to claim 22, wherein the adhesive composition exhibits a peel strength on polyethylene of at least 0.197 N / cm (0.5 N / in), preferably at least 0.591 N / cm (1.5 N / in).

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