Hot melt tts for administering rotigotine

• US 20050260254A1
• Filed: 07/29/2003
• Published: 11/24/2005
• Est. Priority Date: 07/30/2002
• Status: Active Grant

• Current Assignee: Schwarz Pharma, UCB Pharma GmbH (UCB SA)
• Original Assignee: Schwarz Pharma
• Inventors: Breitenbach, Armin, Wolff, Hans-Michael
• Granted Patent: US 9,186,335 B2
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61K 31/381 having five-membered rings
• 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: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• 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

The invention relates to a transdermal therapeutic system (TTS) which contains a rotigotine-containing adhesive layer and is characterized by the fact that the adhesive layer contains a hot-meltable contact adhesive. The invention also relates to the use of rotigotine for producing the adhesive layer of a TTS in a hot melt method, and a method for producing such a TTS.

Claims

1-27. -27. (canceled)

28. A transdermal therapeutic system comprising a drug-containing adhesive matrix, in which the drug is Rotigotine ((−

)-5,6,7,8-tetrahydro-6-[propyl[2-(2- thienyl)ethyl)amino]-1-naphthol) or a prodrug of Rotigotine,

wherein the adhesive matrix contains a hot-meltable adhesive, the hot-meltable adhesive consisting of one adhesive or a mixture of different adhesives or of a mixture of an adhesive and a softener and exhibiting at 160°

C. a dynamic viscosity of not more than 100 Pa·

s.

29. The transdermal therapeutic system of claim 28 wherein Rotigotine or prodrug thereof is dispersed or partly or completely dissolved in said hot-meltable adhesive.

30. The transdermal therapeutic system of claim 28 wherein the drug- containing adhesive matrix is produced by metering the Rotigotine or prodrug thereof into the solvent-free melt of the adhesive matrix at a temperature of between 120°

C. and 160°

C.

31. The transdermal therapeutic system of claim 28 wherein the hot- meltable adhesive consists of a mixture of an amine-resistant silicone adhesive and at least one suitable softener.

32. The transdermal therapeutic system of claim 31 wherein the softener is an organic wax.

33. The transdermal therapeutic system of claim 31 wherein the softener is ceresine or ozokerite.

34. The transdermal therapeutic system of claim 28 wherein the proportion of Rotigotine or prodrug thereof in the adhesive layer is 4 to 40 weight %.

35. The transdermal therapeutic system of claim 28 wherein the proportion of Rotigotine or prodrug thereof in the adhesive layer is 9 to 30 weight %.

36. The transdermal therapeutic system of claim 28 wherein the proportion of Rotigotine or prodrug thereof in the adhesive layer is 20 to 40 weight %.

37. The transdermal therapeutic system of claim 28 wherein Rotigotine or prodrug thereof is present as the active ingredient in form of a base.

38. The transdermal therapeutic system of claim 28 wherein the drug-containing adhesive matrix additionally contains an internal-phase component selected from the group of:

(a) hydrophilic or amphiphilic polymers

(b) hydrophilic or amphiphilic copolymers

(c) mixtures of (a) and/or (b) with pharmaceutically acceptable softeners

(d) condensates from glycerin and fatty acids or polyols

(e) suitable mixtures of the components (a)-(d).

39. The transdermal therapeutic system of claim 38 wherein the internal-phase component is selected from the group of:

polysaccharides, substituted polysaccharides, polyethylene oxides, polyvinyl acetates, polyvinyl pyrrolidones, copolymers from polyvinyl pyrrolidone and (poly)vinyl acetate, polyethylene glycol, polypropylene glycol, copolymers from ethylene and vinyl acetate, glycerin-fatty acid esters as well as mixtures of polyvinyl alcohol with glycerin.

40. The transdermal therapeutic system of claim 28 wherein the adhesive matrix comprises:

(a) 50-99 weight % of said hot-meltable adhesive

(b) 4-40 weight % Rotigotine

(c) 0-40 weight % of an internal-phase component

(d) 0-10 weight % other adjuvants.

41. The transdermal therapeutic system of claim 28 wherein the hot- meltable adhesive is selected from among:

(a1) an EVA adhesive

(a2) an SxS adhesive, or

(a3) a mixture of

(i) 70-99 weight % of an amine-resistant silicone adhesive

(ii) 1-30 weight % of a suitable softener.

42. The transdermal therapeutic system of claim 28 wherein the system comprises Rotigotine.

43. The transdermal therapeutic system of claim 28 wherein the system comprises a prodrug of Rotigotine.

44. The transdermal therapeutic system of claim 43 wherein the prodrug is an ester or carbamate of Rotigotine.

45. A transdermal therapeutic system for administration of Rotigotine, comprising:

a layer that comprises Rotigotine or a prodrug of Rotigotine,

wherein the layer

(a) contains Rotigotine or prodrug thereof in a percentile proportion of at least 20 weight %,

(b) has a Rotigotine or prodrug thereof content of at least 2.0 mg/cm², and

(c) optionally contains an organic wax and/or internal-phase component in an amount sufficient to retard the release of the active substance.

46. The transdermal therapeutic system of claim 45 wherein Rotigotine or prodrug thereof is transported through the skin at a steady-state flux rate of 100-500 μ

g per hour over a period of at least 5 days.

47. The transdermal therapeutic system of claim 45 wherein Rotigotine or prodrug thereof is transported through the human skin at a flux rate of 100-500 μ

g per hour over a period of at least 7 days.

48. The transdermal therapeutic system of claim 45 wherein the system induces in the patient an average plasma concentration of 0.4 to 2 ng/ml Rotigotine for a period of at least 5 days.

49. The transdermal therapeutic system of claim 45 wherein the system comprises Rotigotine.

50. The transdermal therapeutic system of claim 45 wherein the system comprises a prodrug of Rotigotine.

51. The transdermal therapeutic system of claim 50 wherein the prodrug is an ester or carbamate of Rotigotine.

52. A method for producing a transdermal therapeutic system that encompasses an adhesive matrix comprises Rotigotine or a prodrug of Rotigotine as the drug, the method comprising:

prior to lamination components of the adhesive matrix are melted and homogenized, solvent-free, at temperatures of between 70°

C. and 200°

C.

53. The method of claim 52 wherein components of the adhesive matrix are melted and homogenized in an extruder.

54. The method of claim 52 wherein the hot-melting process takes place at temperatures between 120°

C. and 160°

C.

55. The method of claim 52 wherein Rotigotine or prodrug thereof is introduced, in the adhesive matrix melt, in its solid state.

56. The method of claim 52 wherein the adhesive matrix, produced by the hot-melting process, contains Rotigotine or prodrug thereof at a purity level of at least 98% as measured by HPLC at 220 nm and 272 nm.

57. The method of claim 52 wherein the system comprises Rotigotine.

58. The method of claim 52 wherein the system comprises a prodrug of Rotigotine.

59. The method of claim 58 wherein the prodrug is an ester or carbamate of Rotigotine.