Transdermal therapeutic system with high rate of utilization of active substance and dosing accuracy

Abstract

A transdermal therapeutic system for administering at least one active pharmaceutical ingredient, including a polymer-based layer which is remote from the skin with a rate of application of at least 80 g/m.sup.2, and an adhesive skin-contact layer which is adjacent to the polymer-based layer remote from the skin and is based on acrylate copolymers with a rate of application of not more than 50 g/m.sup.2. The at least one active pharmaceutical ingredient is present in both the polymer-based layer remote from the skin and the skin-contact layer.

Claims

1. A transdermal therapeutic system comprising: at least one active pharmaceutical ingredient; a polymer-based layer which is remote from the skin; and an adhesive skin-contact layer which is adjacent to the polymer-based layer remote from the skin and is based on acrylate copolymers; wherein a coating weight of the polymer-based layer remote from the skin is at least 80 g/m.sup.2 and a coating weight of the skin-contact layer is not more than 50 g/m.sup.2; and wherein the at least one active pharmaceutical ingredient is present in both the polymer-based layer remote from the skin and the skin-contact layer.

2. The transdermal therapeutic system as claimed in claim 1; wherein the mass per area of the polymer-based layer remote from the skin is 100-200 g/m.sup.2.

3. The transdermal therapeutic system as claimed in claim 1; wherein the mass per area of the skin-contact layer is 20-30 g/m.sup.2.

4. The transdermal therapeutic system as claimed in claim 1; wherein the ratio of the mass per area of the polymer-based layer remote from the skin to that of the skin-contact layer is at least 2:1.

5. The transdermal therapeutic system as claimed in claim 4; wherein the ratio is from 3:1 to 5:1.

6. The transdermal therapeutic system as claimed in claim 1; wherein, after production of the system and diffusion equalization, a majority of the at least one active ingredient is located in the skin-contact layer.

7. The transdermal therapeutic system as claimed in claim 1; wherein the acrylate copolymers of the skin-contact layer comprise at least one monomer unit selected from the group consisting of acrylic acid, methacrylic acid, acrylic esters, and methacrylic esters.

8. The transdermal therapeutic system as claimed in claim 1; wherein the acrylate copolymers of the skin-contact layer additionally comprise vinyl acetate.

9. The transdermal therapeutic system as claimed in claim 1; wherein the at least one active ingredient is selected from the group of analgesics, bronchodilators, antidiabetics, vasodilators, anticraving agents, and antiparkinson agents.

10. The transdermal therapeutic system as claimed in claim 9; wherein the at least one active ingredient is an analgesic.

11. The transdermal therapeutic system as claimed in claim 10; wherein at least one of the active ingredients is an opioid.

12. The transdermal therapeutic system as claimed in claim 11; wherein the opioid is fentanyl and/or one of its derivatives.

13. The transdermal therapeutic system as claimed in claim 12; wherein the fentanyl derivative is alfentanil, sufentanil, or remifentanil.

14. A process for producing a transdermal therapeutic system as claimed in claim 1, comprising: forming a mixture by mixing the at least one active ingredient, which is dissolved in a suitable volatile solvent or solvent mixture, with a polymer composition which is intended for the polymer-based layer remote from the skin; forming the the polymer-based layer remote from the skin by: applying the mixture uniformly in a layer thickness of at least 200 μm to a siliconized plastic sheet; drying and evaporation of the solvent; and laminating the adhesive skin-contact layer onto the polymer-based layer remote from the skin in such a way that the active ingredient-containing polymer-based layer remote from the skin and the adhesive skin-contact layer are in contact with one another.

15. The process as claimed in claim 14; wherein the polymer-based layer remote from the skin and the skin-contact layer are laminated together in such a way that migration of the at least one active ingredient out of the former into the latter is made possible.

16. The process as claimed in claim 14; wherein the mass per area of the polymer-based layer remote from the skin is 100-200 g/m.sup.2 and the mass per area of the skin-contact layer is 20-30 g/m.sup.2.

17. The process as claimed in claim 16; wherein the ratio of the mass per area of the polymer-based layer remote from the skin to that of the skin-contact layer is at least 2:1.

18. The process as claimed in claim 17; wherein the ratio is from 3:1 to 5:1.

19. The process as claimed in claim 14; wherein the at least one active ingredient is fentanyl or a fentanyl derivative.

20. The process as claimed in claim 19; wherein the fentanyl derivative is alfentanil, sufentanil, or remifentanil.

21. A transdermal therapeutic system for administering at least one active pharmaceutical ingredient, with a daily dose in a range of from 1 mg to 500 mg, comprising: a polymer-based layer which is remote from the skin; and an adhesive skin-contact layer which is adjacent to the polymer-based layer remote from the skin and is based on acrylate copolymers; wherein a mass per area of the polymer-based layer remote from the skin is at least 80 g/m.sup.2 and a mass per area of the skin-contact layer is not more than 50 g/m.sup.2; and wherein the at least one active pharmaceutical ingredient is present in both the polymer-based layer remote from the skin and the skin-contact layer.

22. A transdermal therapeutic system for administering at least one active pharmaceutical ingredient, with a daily dose not exceeding 30 mg, comprising: a polymer-based layer which is remote from the skin; and an adhesive skin-contact layer which is adjacent to the polymer-based layer remote from the skin and is based on acrylate copolymers; wherein a coating weight of the polymer-based layer remote from the skin is at least 80 g/m.sup.2 and a coating weight of the skin-contact layer is not more than 50 g/m.sup.2; and wherein the at least one active pharmaceutical ingredient is present in both the polymer-based layer remote from the skin and the skin-contact layer.

Description

EXAMPLE 1

(1) A solution of polyacrylic acid-co-2-ethylhexyl acrylate-co-vinyl acetate, 30% (w/w) in ethyl acetate is coated in a layer thickness of about 65-70 μm onto a siliconized polyethylene terephthalate sheet (100 μm thick) and dried in the open at 25° C. for 2 hours to result in an adhesive layer of 20 g/m.sup.2. In a separate operation, 2 g of fentanyl base, 70 g of polyisobutylene 100, 28 g of polyisobutylene 10, 100 g of methyl ethyl ketone and 200 g of n-heptane are made into a viscous solution and then stirred for 2 hours. This phase is coated with a layer thickness of about 500 μm onto a 15 μm thick sheet of polyethylene terephthalate to result in an active ingredient-containing dry adhesive layer of 100 g/m.sup.2. This layer is laminated on the adhesive side with the previously fabricated acrylate copolymer layer (adhesive layer onto adhesive layer) so that a continuous, two-layer matrix is produced. Detachment of the protective sheet produces an adhesive system which can be stuck with the polyacrylate side onto the skin. The system can be cut to the required size by suitable cutting devices.

EXAMPLE 2

(2) A solution of poly(2-ethylhexyl acrylate-co-vinyl acetate-co-2-hydroxyethyl acrylate-co-2,3-epoxypropyl methacrylate), 30% (w/w) in ethyl acetate is coated in a layer thickness of about 65-70 μm onto a siliconized polyethylene terephthalate sheet (100 μm thick) and dried in the open at 25° C. for 2 hours to result in an adhesive layer of 20 g/m.sup.2. In a separate operation, 1.5 g of fentanyl base, 70 g of polyisobutylene 100, 28 g of polyisobutylene 10, 100 g of methyl ethyl ketone and 200 g of n-heptane are made into a viscous solution and then stirred for 2 hours. This phase is coated with a layer thickness of about 500 μm onto a 15 μm-thick sheet of polyethylene terephthalate to result in an active ingredient-containing dry adhesive layer of 100 g/m.sup.2.

(3) This layer is laminated on the adhesive side with the previously fabricated acrylate copolymer layer (adhesive layer onto adhesive layer) so that a continuous, two-layer matrix is produced. Detachment of the protective sheet produces an adhesive system which can be stuck with the polyacrylate side onto the skin. The system can be cut to the required size by suitable cutting devices.