Transdermal therapeutic system which contains a d2 agonist and which is provided for treating parkinsonism, and a method for the production thereof
View Patent ↗A transdermal therapeutic system, comprising a backing layer inert to the components of the matrix, a self-adhesive matrix layer containing (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol in an effective amount and a protective foil or sheet to be removed prior to use, is characterised by a matrix that is based on a non-aqueous, acrylate-based or silicone-based polymer adhesive system having a solubility of ≧5% (w/w) for (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]-amino]-1-naphthalenol, and said matrix is substantially free of inorganic silicate particulates.
1. A transdermal therapeutic system comprising a self-adhesive matrix layer containing the free base (−)-5,6,7,8-tetrahydro-6-[propyl-1[2-(2-thienyl)ethyl]amino]-1-naphthalenol in an amount effective for the treatment of the symptoms of Parkinson's syndrome, wherein the matrix is based on a an acrylate-based or silicone-based polymer adhesive system having a solubility of ≧5% (w/w) for the free base (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]-amino]-1-naphthalenol, all of said free base being present in the matrix in the absence of water; a backing layer inert to the components of the matrix layer; and a protective foil or sheet covering the matrix layer to be removed prior to use.
2. The transdermal therapeutic system of claim 1 further comprising <0.5% (w/w) inorganic silicate particulates in the matrix layer.
3. The transdermal therapeutic system of claim 1 further comprising <0.05% (w/w) inorganic silicate particulates in the matrix layer.
4. The transdermal therapeutic system of claim 1 wherein the acrylate-based polymer adhesive in the matrix layer contains at least two monomers selected from the group of acrylic acid, acrylamide, hexylacrylate, 2-ethylhexylacrylate, hydroxyethylacrylate, octylacrylate, butylacrylate, methylacrylate, glycidylacrylate, methacrylic acid, methacrylamide, hexylmethacrylate, 2-ethyhexylmethacrylate, octylmethacrylate, methylmethacrylate, glycidylmethacrylate, vinylacetate and vinylpyrrolidone.
5. The transdermal therapeutic system of claim 1 wherein the silicone-based polymer adhesive in the matrix layer further comprises additives to enhance the solubility of (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol in the form of hydrophilic polymers or glycerol or glycerol derivatives.
6. The transdermal therapeutic system of claim 4 wherein the acrylate-based polymer contains between 10 to 40% (w/w) (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]-amino]-1-naphthalenol.
7. The transdermal therapeutic system of claim 5 wherein the silicone-based polymer adhesive contains between 5 to 25% (w/w) (−)-5,6,7,8-tetrahydro[propyl-[2-(2-thienyl)ethyl]-amino]-1-naphthalenol.
8. The transdermal therapeutic system of claim 6 further comprising substances which enhance the permeation of (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol into the human skin.
9. The transdermal therapeutic system of claim 7 further comprising substances which enhance the permeation of (−)-5,6,7, 8-tetrahydro-6-[propyl-[2-(2a thienyl)ethyl]amino]-1-naphthalenol into the human skin.
10. The transdermal therapeutic system of claim 8 wherein the permeation-enhancing substance is selected from the group of fatty alcohols, fatty acids, fatty acid esters, fatty acid amides, glycerol or its derivatives, N-methyl-pyrrolidone, terpenes, and terpene derivatives.
11. The transdermal therapeutic system of claim 9 wherein the permeation-enhancing substance is selected from the group of fatty alcohols, fatty acids, fatty acid esters, fatty acid amides, glycerol or its derivatives, N-methyl-pyrrolidone, terpenes, and terpene derivatives.
12. The transdermal therapeutic system of claim 10 wherein the permeation-enhancing substance is oleic acid or oleyl alcohol.
13. The transdermal therapeutic system of claim 11 wherein the permeation-enhancing substance is oleic acid or oleyl alcohol.
14. The transdermal therapeutic system of claim 5 , wherein the hydrophilic polymer is selected from the group of polyvinylpyrrolidone, a copolymer of vinylpyrrolidone and vinylacetate, polyethyleneglycol, polypropylene glycol, and a copolymer of ethylene and vinylacetate.
15. The transdermal therapeutic system of claim 14 wherein the hydrophilic polymer is soluble polyvinylpyrrolidone, and wherein the soluble polyvinylpyrrolidone is present in the active substance-containing matrix layer at a concentration of between 1.5 and 5% (w/w).
16. The transdermal system of claim 1 wherein the matrix further comprises inert fillers to improve cohesion.