TRANSDERMAL THERAPEUTIC SYSTEM WITH DIFFUSION BARRIER

Abstract

The present invention relates to a transdermal therapeutic system (1) comprising an active-substance carrier layer (2) having at least one active-substance-containing polymer matrix (3) applied to the active-substance carrier layer (2), said matrix comprising at least one pressure-sensitive adhesive and at least one pharmacologically active substance absorbable through human or animal skin, and an adhesive carrier layer (6) coated as completely as possible with an active-substance-free pressure-sensitive adhesive (7), said adhesive carrier layer being bonded by means of the active-substance-free pressure-sensitive adhesive (7) directly to the flat side of the active-substance carrier layer (2) facing away from the active-substance-containing polymer matrix (3),
wherein the adhesive carrier layer (6) projecting circumferentially beyond the edge of the active-substance carrier layer (2), wherein the system is characterized in that between the active-substance-containing polymer matrix (3) and the active-substance-free pressure-sensitive adhesive (7) there is a circumferential zone (4) having a reduced thickness of coating with the active-substance-containing polymer matrix (3) and/or with the active-substance-free pressure-sensitive adhesive (7). The invention further relates to the use of this transdermal therapeutic system and to a kit that contains it.

Claims

1.-15. (canceled)

16. A transdermal therapeutic system comprising an active-substance carrier layer having at least one active-substance-containing polymer matrix applied to the active-substance carrier layer, said matrix comprising at least one pressure-sensitive adhesive and at least one pharmacologically active substance absorbable through human or animal skin, and an adhesive carrier layer coated as completely as possible with an active-substance-free pressure-sensitive adhesive, said adhesive carrier layer being bonded by means of the active-substance-free pressure-sensitive adhesive directly to the flat side of the active-substance carrier layer facing away from the active-substance-containing polymer matrix, the adhesive carrier layer projecting circumferentially beyond the edge of the active-substance carrier layer, wherein between the active-substance-containing polymer matrix and the active-substance-free pressure-sensitive adhesive there is a circumferential zone having a reduced thickness of coating with the active-substance-containing polymer matrix and/or with the active-substance-free pressure-sensitive adhesive.

17. The system as claimed in claim 16, wherein the adhesive carrier layer is coated as completely as possible with the active-substance-free pressure-sensitive adhesive and is bonded to the active-substance carrier layer, wherein the active-substance carrier layer has a circumferential edge zone having a reduced thickness of coating with the active-substance-containing polymer matrix.

18. The system as claimed in claim 17, wherein the circumferential edge zone having a reduced thickness of coating is produced or producible by guiding a punching tool onto the material for the active-substance carrier layer that is coated over its entire surface with active-substance-containing polymer matrix, said tool comprising a hollow cylinder and a cutting blade arranged to the outside of the hollow cylinder, more particularly concentrically and directly adjoining it, the hollow cylinder being first pressed onto the coated active-substance carrier layer, causing a reduction in the thickness of coating with the active-substance-containing polymer matrix, after which the cutting blade is used to punch out the active-substance carrier layer with a circumferential edge zone having a reduced thickness of coating with the active-substance-containing polymer matrix.

19. The system as claimed in claim 16, wherein the adhesive carrier layer, where it borders the active-substance carrier layer, has a circumferential zone having a reduced thickness of coating with the active-substance-free pressure-sensitive adhesive.

20. The system as claimed in claim 16, wherein, in the system, the active-substance-containing polymer matrix is applied directly to the active-substance carrier layer and the active-substance-free pressure-sensitive adhesive directly to the adhesive carrier layer, there being no further layer between the flat side of the active-substance carrier layer facing away from the active-substance-containing polymer matrix and the active-substance-free pressure-sensitive adhesive of the adhesive carrier layer.

21. The system as claimed in claim 16, wherein the polymer matrix of the active-substance-containing polymer matrix and of the active-substance-free pressure-sensitive adhesive is independently selected from acrylates, silicone pressure-sensitive adhesives, polyisobutylenes, SIS copolymers, silicone-acrylate hybrid systems, and mixtures thereof.

22. The system as claimed in claim 16, wherein the pharmacologically active substance is selected from the group consisting of α-adrenergic agonists, β-adrenergic agonists, α-adrenergic antagonists, β-adrenergic antagonists, analgesics (narcosis-inducing), analgesics (non-narcosis-inducing), androgens, anesthetics, antiallergic s, antiandrogens, antianginals, antiarrhythmics, penicillins, antidiabetics, antidementia drugs, antihistamines, antimigraine drugs, hydrogenated ergot alkaloids, calcium-channel blockers, hormones, serotonin antagonists, platelet-aggregation inhibitors, antidepressants, bronchodilators, estrogens, gestagens, vasodilators and nicotine or mixtures thereof.

23. The system as claimed in claim 16, wherein the circumferential zone of reduced coating thickness is not more than 20% of the thickness of the polymer matrix of the active-substance-containing polymer matrix and/or of the active-substance-free pressure-sensitive adhesive, in particular not more than 15%.

24. The system as claimed in claim 16, wherein the circumferential zone of reduced coating thickness has a width of 0.05 to 5.0 mm.

25. The system as claimed in claim 16, wherein the circumferential zone of reduced coating thickness is essentially unbroken.

26. The system as claimed in claim 16, wherein the coating thickness of the active-substance-containing polymer matrix and/or of the active-substance-free pressure-sensitive adhesive is 20 to 800 μm.

27. The system as claimed in claim 16, wherein a protective layer covering the entire surface of the polymer matrix of the active-substance-containing polymer matrix and of the active-substance-free pressure-sensitive adhesive is provided, wherein the protective layer on the flat side facing the active-substance-containing polymer matrix is equipped in particular with an adhesion-reducing coating.

28. A process for producing a transdermal therapeutic system as claimed in claim 16, comprising the steps of providing an active-substance carrier layer having at least one active-substance-containing polymer matrix applied to the active-substance carrier layer, said matrix comprising at least one pressure-sensitive adhesive and at least one pharmacologically active substance absorbable through human or animal skin, and bonding an adhesive carrier layer coated as completely as possible with an active-substance-free pressure-sensitive adhesive by means of the active-substance-free pressure-sensitive adhesive directly to the flat side of the active-substance carrier layer facing away from the active-substance-containing polymer matrix, wherein the adhesive carrier layer projecting circumferentially beyond the edge of the active-substance carrier layer, wherein between the active-substance-containing polymer matrix and the active-substance-free pressure-sensitive adhesive there is a circumferential zone having a reduced thickness of coating with the active-substance-containing polymer matrix and/or with the active-substance-free pressure-sensitive adhesive, wherein the circumferential edge zone with a reduced thickness of coating being produced by guiding a punching tool onto the material for the active-substance carrier layer that is coated over its entire surface with active-substance-containing polymer matrix, said tool comprising a hollow cylinder and a cutting blade arranged to the outside of the hollow cylinder, more particularly concentrically and directly adjoining it, the hollow cylinder being first pressed onto the coated active-substance carrier layer, causing a reduction in the thickness of coating with the active-substance-containing polymer matrix, after which the cutting blade is used to punch out the active-substance carrier layer with a circumferential edge zone having a reduced thickness of coating with the active-substance-containing polymer matrix.

29. A method comprising utilizing the transdermal therapeutic system as claimed in claim 16 for the treatment of the animal or human body, wherein the treatment is selected from hypogonadism, hormone replacement therapy, Alzheimer's, of Parkinson's, of multiple sclerosis, bipolar disorders, muscle tension, severe pain, high blood pressure or for contraception.

30. A kit comprising at least one transdermal therapeutic system as claimed in claim 16 in an outer packaging and instructions for use.

Description

EXAMPLE(S)

[0055] The present invention is elucidated in more detail hereinbelow with reference to the working examples shown in FIGS. 1 and 2. In the figures

[0056] FIG. 1 shows an intermediate stage in the production of a transdermal therapeutic system according to the invention, and

[0057] FIG. 2 shows an embodiment of the finished transdermal therapeutic system according to the invention as shown in FIG. 2.

[0058] FIG. 2 depicts an embodiment of a transdermal therapeutic system 1 according to the invention. The transdermal therapeutic system 1 comprises an active-substance carrier layer 2 having at least one active-substance-containing polymer matrix 3 applied to the active-substance carrier layer 2, said matrix comprising at least one pressure-sensitive adhesive and at least one pharmacologically active substance absorbable through human or animal skin, in the present case scopolamine. The active-substance carrier layer 2 has a circumferential edge zone 4 having a reduced thickness of coating with the active-substance-containing polymer matrix and is applied onto a protective layer 5 that covers the entire surface of the active-substance-containing polymer matrix 3 and projects beyond this at the edge and is provided with a silicone coating to reduce adhesion of the pressure-sensitive adhesive.

[0059] On the flat side facing the active-substance-containing polymer matrix 3, the active-substance carrier layer 2 is completely covered by an adhesive carrier layer 6, which is bonded directly to the active-substance carrier layer 2 by means of an active-substance-free pressure-sensitive adhesive 7. The adhesive carrier layer 6 is coated over its entire surface with the active-substance-free pressure-sensitive adhesive 7. The bonding of the adhesive carrier layer 6 to the active-substance carrier layer 2 results in the circumferential zone 4 with a reduced thickness of coating with the active-substance-containing polymer matrix being bent over all the way round. Both the pressure-sensitive adhesive of the active-substance-containing polymer matrix 3 and the active-substance-free pressure-sensitive adhesive 7 are in the present case a silicone-based pressure-sensitive adhesive.

[0060] In the production of the transdermal therapeutic system 1 according to the invention, an active-substance carrier layer 2 is first coated with an active-substance-containing polymer matrix 3 comprising at least one pressure-sensitive adhesive, in the present case a silicone-based pressure-sensitive adhesive, and at least one pharmacologically active substance absorbable through human or animal skin, in the present case scopolamine. Onto the material for the active-substance carrier layer 2 that is initially coated over its entire surface with active-substance-containing polymer matrix 3 is guided a punching tool that comprises a hollow cylinder and a cutting blade arranged to the outside of the hollow cylinder and concentrically and directly adjoining it. In this process, the hollow cylinder is first pressed onto the coated active-substance carrier layer 2, causing a reduction in the thickness of coating with the active-substance-containing polymer matrix, with the result that a circumferential zone 4 having a reduced thickness of coating with the active-substance-containing polymer matrix is obtained. The cutting blade is then used to punch out the active substance carrier layer 2 outside the circumferential zone 4 having a reduced thickness of coating, which is applied onto a protective layer 5 furnished with a silicone coating, said protective layer completely covering the active-substance-containing polymer matrix 3 and projecting beyond the edge. In this process, the active-substance-containing polymer matrix 3 can be completely or largely completely removed in the area of the hollow cylinder, depending on the contact pressure of the hollow cylinder and the softness of the active-substance-containing polymer matrix 3. This affords an intermediate product 10, the layer structure of which is shown in FIG. 1.

[0061] On the flat side of the intermediate product 10 facing the active-substance-containing polymer matrix 3, the entire surface of the active-substance carrier layer 2 is covered by an adhesive carrier layer 6, which is bonded directly to the active-substance carrier layer 2 by means of an active-substance-free pressure-sensitive adhesive 7, affording the transdermal therapeutic system 1 of the invention. In this case too, a silicone-based pressure-sensitive adhesive is used. The bonding of the adhesive carrier layer 6 to the active-substance carrier layer 2 results in the circumferential zone 4 with a reduced thickness of coating with the active-substance-containing polymer matrix being bent over all the way round, but without this affecting its ability to act as a diffusion barrier.

[0062] After production, the transdermal therapeutic system 1 thus produced is hermetically sealed inside individual aluminum-laminated polyester film packagings and subjected to storage in a climatic chamber for 6 months at 40° C. and 75% relative humidity. The transdermal therapeutic system 1 is then taken out of the packaging and investigated for possible migration of the scopolamine. In these investigations, no scopolamine was detected in the active-substance-free pressure-sensitive adhesive 7.

[0063] To apply the transdermal therapeutic system 1 of the invention, the protective layer 5 is peeled off and the remaining layer structure is placed adhesive-side down on the desired area of skin and pressure applied.

[0064] Even after detachment of the transdermal therapeutic system 1 of the invention from the skin after a period of use of 1-2 days, analyses detected no scopolamine in the active-substance-free pressure-sensitive adhesive 7 in the zone where the adhesive carrier layer 6 projects beyond the active-substance carrier layer 2.