Method for producing a transdermal therapeutic system which contains a D2 agonist

• US 10,322,093 B2
• Filed: 09/07/2004
• Issued: 06/18/2019
• Est. Priority Date: 03/30/1998
• Status: Expired due to Fees

• Current Assignee: Ucb Biopharma Sprl (UCB SA)
• Original Assignee: LTS Lohmann Therapie-Systeme AG, Ucb Biopharma Sprl (UCB SA)
• Inventors: Mueller, Walter, Peck, James V.
• Primary Examiner(s): Ghali, Isis A
• Application Number:
  US10/936,620
• Publication Number:
  US 20050033065A1
• Time in Patent Office: 5,397 Days
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7038 Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61K 9/7092 Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A substantially solvent-free matrix layer containing (−)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol is produced by adding an active substance to an adhesive solution, coating the resultant active substance-containing adhesive solution onto a suitable sheet, and removing the solvents in a drying process to give said substantially solvent-free matrix layer.

Claims

1. A method for producing a matrix layer suitable for transdermal administration of a therapeutic effective amount of (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base, the method comprising;

(a) mixing a solution comprising (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base and organic solvent with soluble polyvinylpyrrolidone and amine-resistant silicone adhesive to form a mass;

(b) coating the mass onto a sheet; and

(c) removing solvent in a drying process.

2. The method of claim 1, wherein the (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base is prepared by converting (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride into said free base.

3. The method of claim 2, wherein said (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride is dissolved or suspended in said organic solvent.

4. The method of claim 2, wherein an alkaline substance capable of converting said (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride into the free base is added to the organic solvent prior to or following addition thereto of the adhesive and prior to or following addition thereto of the (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride.

5. The method of claim 4, wherein said alkaline substance comprises an alkali metal hydroxide or an alkali metal silicate.

6. The method of claim 4, wherein said alkaline substance comprises at least one member selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium trisilicate, potassium trisilicate, sodium metasilicate and potassium metasilicate.

7. The method of claim 6, wherein following reaction of (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride with the alkaline substance, the resulting adhesive solution containing (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base is filtered to remove at least one by-product selected from the group consisting of sodium chloride, potassium chloride and polymeric silicon dioxide.

8. The method of claim 1, further comprising admixing with said solution at least one permeation enhancer selected from the group consisting of fatty alcohols, fatty acids, fatty acid esters, fatty acid amides, glycerol, fatty acid esters of glycerol, N-methyl-pyrrolidone, terpenes, limonene, a-pinene, a-terpineol, carvone, carveol, limonene oxide, pinene oxide and 1,8-eucalyptol.

9. The method of claim 1, wherein the matrix layer has a solubility for (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base of ≥

5% (w/w).

10. The method of claim 1, wherein (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base is contained in the matrix in a concentration of from 5% to 25% (w/w).

11. The method of claim 1, wherein the soluble polyvinylpyrrolidone is admixed to provide a concentration of 1.5-5% (w/w) soluble polyvinylpyrrolidone in the matrix layer.

12. The method of claim 1, wherein the organic solvent comprises ethanol.

13. The method of claim 4, wherein following reaction of (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol hydrochloride with the alkaline substance, the resulting adhesive solution containing (−

)-5,6,7,8-tetrahydro-6-[propyl-[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base is filtered to remove at least one by-product.

14. The method of claim 1, wherein the resulting matrix layer is a non-aqueous matrix layer.

15. The method of claim 1, wherein the matrix layer is a single-phase matrix.

16. The method of claim 11, wherein the soluble polyvinylpyrrolidone is admixed in an amount to provide a concentration of 1.5-3% (w/w) soluble polyvinylpyrrolidone in the matrix layer.

17. The method of claim 1, further comprising preparing a plaster having an area of 2 to 40 cm² from the matrix layer, said plaster containing 1 to 10 mg of the (−

)-5,6,7,8-tetrahydro-6-[propyl-1[2-(2-thienyl)ethyl]amino]-1-naphthalenol free base.

18. The method of claim 17, wherein the plaster has an area of approximately 20 cm².

19. The method of claim 1, wherein a backing layer is applied to the matrix layer on the side thereof opposing said sheet, and wherein said sheet forms a removable protective layer.