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(12) Patent Application Publication (10) Pub. No.: US 2005/0142174A1 Assmus Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2005/0142174A1 Assmus Et Al US 2005O142174A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0142174A1 ASSmus et al. (43) Pub. Date: Jun. 30, 2005 (54) ADHESIVE AND BINDING AGENT FOR (30) Foreign Application Priority Data DERMAL OR TRANSIDERMAL TREATMENT SYSTEMS Jan. 9, 2002 (DE)........................................ 10200578.8 (75) Inventors: Manfred Assmus, Bickenbach (DE); Publication Classification Erna Roth, Darmstadt (DE), Antoni (51) Int. Cl." .......................... A61K 31/485; A61 K 9/70 Boix, St. Joan (ES); Isabel Reig, St. (52) U.S. Cl. ............................................ 424/449; 514/282 Joan Despi (ES) s (57) ABSTRACT Correspondence Address: The invention relates to an adhesive and binding agent for OBLON, SPIVAK, MCCLELLAND, MAIER & dermal or transdermal treatment Systems, said agent con NEUSTADT, P.C. taining (a) a (meth)acrylate copolymer consisting of radi 1940 DUKE STREET cally polymerised C-sb>1</sb>to C-sb>4</sb>alkyl esters ALEXANDRIA, VA 22314 (US) of acrylic or methacrylic acid and (meth)acrylate monomers having a cationic ammonium group in the alkyl radical; (b) between 0.1 and 45 wt.%, in relation to (a), of an organic (73) Assignee: Roehm GMBH & Co. KG dicarboxylic or tricarboxylic acid, or of acrylate or (meth )acrylate polymers or copolymers containing acid groups; (21) Appl. No.: 10/499,818 (c) a skin penetration enhancer; and (d) optionally a phar maceutical active ingredient, a Softener and/or at least one (22) PCT Filed: Dec. 19, 2002 Standard addition agent. The inventive adhesive and binding agent is characterised in that the penetration enhancer (c) is (86) PCT No.: PCT/EPO2/14556 an alcohol comprising between 10 and 12 carbon atoms. US 2005/0142174 A1 Jun. 30, 2005 ADHESIVE AND BINDING AGENT FOR DERMAL number of parameters are met Simultaneously. Suitable OR TRANSIDERMAL TREATMENT SYSTEMS methods of determining these parameters, which are speci fied below, are familiar to the skilled worker in the field of 0001. The invention relates to an adhesive and binder for dermal or transdermal therapeutic Systems (on this point See dermal or transdermal therapeutic Systems. Prior art also the remarks in the “Examples' section). 0002 EP-A 315 218 describes pharmaceutical composi tions intended for the Systemic transdermal administration of 0010 Mention should be made first of all of a sufficient active pharmacological Substances and characterized in that bond Strength, which ought though to be only So high that the active pharmacological Substances are located in a when the adhesive layer is detached there is adhesive reservoir that comprises a polyacrylate polymer having fracture but not cohesive fracture. cationic properties. Plasticizers and can be present in 0011. In addition there are minimum requirements to be amounts of from 3 to 33% by weight. Penetration enhancers met in terms of the properties of tack and cold flow. The tack can be present in amounts from 10 to 100% by weight. The ought generally to be at least 1 and the cold flow not more pharmaceutical composition may further be provided with than 1 mm/24 hours. an adhesive layer in order to achieve effective adhesion to the skin. 0012 Finally, an active pharmaceutical substance present 0003) EP-A 617.972 describes laminar dermal therapeu ought to penetrate the Skin effectively. Penetration figures of tic Systems with retarded release of active Substance which at least 1 lug active Substance/cm are the target. are composed of mixtures of poly(meth)acrylates and are 0013 The latter objective in particular is difficult to prepared from a melt. One poly(meth)acrylate component achieve, Since it requires the addition of comparatively high contains functional groups while another poly(meth)acrylate proportions of penetration enhancers, which are known per component contains insignificant amounts of functional Se. The relatively high proportions required have an effect on groups, if any, and essentially regulates the flow behavior of the overall System, alongside other requisite components the polymeric adhesive layer. Penetration enhancers are Such as plasticizers, which is generally negative. If, on the mentioned as possible additives. other hand, the amount of other components, Such as the 0004 EP-A 848 950 and EP-A 848 960 describe adhe amount of the plasticizer, for example, is lowered in favor of Sives and binders for pharmaceutical purposes that are the penetration enhancer, the desired penetration rate is distinguished by high hydrophilicity and/or high water achieved but the other properties, particularly the bond Vapor permeability and at the Same time combine a high strength, are then generally no longer within the target range. bond strength with low cold flow. The adhesives and binders 0014. The problem was therefore seen to be to provide an are therefore outstandingly Suitable as pressure-Sensitive adhesive and binder for dermal or transdermal therapeutic skin adhesives or transdermal therapeutic Systems. Systems that as far as possible meets all of the abovemen 0005 EP-A 0848960 describes an adhesive and binder tioned criteria Simultaneously. A further target ought to be to for dermal or transdermal therapeutic Systems which con lower the amount of plasticizing Substances which do not sists of (a1) 55-99.9% by weight of a (meth)acrylate copoly enhance penetration, as far as is possible, or to do without mer formed from Structural and functional monomers, the them entirely, So that the amount of the other ingredients and functional monomers containing tertiary or quaternary additives does not become too high with respect to the amino groups, (a2) 0.1-45% by weight of an acid-functional amount of the actual matrix-forming System, So that, for acrylate or (meth)acrylate polymer or copolymer, and (b) example, controlled release of active Substance is unaf 25-80% by weight, based on the sum of (a1) and (a2), of a fected. plasticizer. 0015 Surprisingly it has been found that the problem is 0006 EP-A848 950 describes an adhesive and binder for solved by means of dermal or transdermal therapeutic Systems which consists of 0016 an adhesive and binder for transdermal therapeutic (a) 85-99% by weight of a (meth)acrylate copolymer formed Systems, comprising from Structural and functional monomers, the functional monomers containing tertiary or quaternary amino groups, 0017 (a) a (meth)acrylate copolymer of free-radically (b) 15-0.1% by weight of an organic dicarboxylic or tricar polymerized C to C alkyl esters of acrylic or methacrylic boxylic acid and (c) 40-70% by weight, based on the sum of acid and (meth)acrylate monomers having a cationic ammo (a) and (b), of a plasticizer. nium group in the alkyl radical, comprising 0007 DE 4020 144 C2 describes a device for the topical 0018 (b) 0.1-45% by weight based on (a) of an organic and Systemic administration of active Substances. The SyS dicarboxylic or tricarboxylic acid or of an acid- functional tems in question are mixtures of polyacrylate adhesive with acrylate or (meth)acrylate polymer or copolymer, and a film former, e.g., a neutral copolymer of methyl methacry late and butyl methacrylate (PLASMID(R) B), which may 0019 (c) a skin penetration enhancer comprise plasticizing auxiliaries Such as Solubilizers or penetration enhancers, e.g., fatty alcohols Such dodecanol, in 0020 (d) if desired, an active pharmaceutical substance, amounts of, for example, 20% by weight. a plasticizer and/or one or more customary pharmaceutical additives 0008 Problem and Solution 0021) characterized in that 0009. A fundamental issue affecting adhesives and bind erS for dermal or transdermal therapeutic Systems is the 0022 the penetration enhancer (c) is an alcohol having 10 harmonization of the components in Such a way that a to 12 carbon atoms. US 2005/0142174 A1 Jun. 30, 2005 Implementation of the Invention means of Solution or precipitation polymerization. In this way the polymer may be obtained in the form of a fine 0023 Component (a) powder, which in the case of bulk polymerization can be 0024 Component (a) is a (meth)acrylate copolymer com achieved by grinding and in the case of Solution and pre posed of free-radically polymerized C to C alkyl esters of cipitation polymerization by Spray drying, for example. A acrylic or methacrylic acid and (meth)acrylate monomers corresponding copolymer may be Synthesized, for example, having a cationic ammonium group in the alkyl radical. This from 50-70% by weight of methyl methacrylate, 20-40% by definition embraces copolymers which, under product weight of ethyl acrylate, and 7-2% by weight of 2-trimethy names including EUDRAGITE) E, EUDRAGIT(R) RS or lammonioethyl methacrylate chloride. EUDRAGIT(RRL, have been known for a long time as drug 0033) Another suitable (meth)acrylate copolymer may be coatings. synthesized, for example, from 85 to less than 93% by 0025 The amount of the (meth)acrylate monomers hav weight of C1 to C4alkyl esters of acrylic or methacrylic acid ing a cationic ammonium group in the alkyl radical is and more than 7 to 15% by weight of (meth)acrylate preferably at least 2%, more preferably at least 4% by monomers having a quaternary ammonium group in the weight based on the copolymer. alkyl radical. (Meth)acrylate monomers of this kind are commercially customary and have long been used for retar 0026 C to C alkyl esters of acrylic or methacrylic acid dant coatings. are, in particular, methyl acrylate, ethyl acrylate, butyl acrylate, butyl methacrylate, and methyl methacrylate. 0034 A(meth)acrylate copolymer corresponding to com ponent (a) and containing quaternary amino groups may be 0027 (Meth)acrylate monomers having a cationic ammo synthesized, for example, from 60% by weight of methyl nium group in the alkyl radical are, in particular, (meth methacrylate, 30% by weight of ethyl acrylate, and 10% by )acrylate monomers having tertiary or quaternary amino weight of 2-trimethylammonioethyl methacrylate chloride and/or ammonium groups in the alkyl radical.
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