Rotigotine Patch Adhesive Layer Crystallization Prevention

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Solution Overview

Problem

Rotigotine-containing patches face challenges with rotigotine precipitating into crystals over time, reducing skin permeability and stability, especially when using conventional adhesives like silicone or acrylic-based agents, and antioxidants do not adequately address these issues.

Innovation Solution

Incorporating rotigotine and its pharmaceutically acceptable salts into an adhesive layer with a styrene-based thermoplastic elastomer, petroleum-based or terpene-based resins, an aliphatic alcohol, and cross-linked polyvinylpyrrolidone, maintaining a specific mass ratio to ensure rotigotine remains dissolved and stable.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If rotigotine is contained in an amorphous form in the presence of rotigotine alone or polyvinylpyrrolidone, then the drug can be incorporated into the patch, but the amorphous form transforms into a crystal form over time causing precipitation

Engineering Contradiction:
Improverotigotine incorporationVSAvoidamorphous form stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent introduces cross-linked polyvinylpyrrolidone as an intermediary substance that mediates between rotigotine and the adhesive base agent. This cross-linked polymer prevents the transformation from amorphous to crystalline form by acting as a stabilizing matrix, thereby maintaining rotigotine in a dissolved state without precipitation while still allowing adequate drug incorporation into the patch.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the polyvinylpyrrolidone by using its cross-linked form rather than the conventional non-cross-linked form. This parameter change (from linear to cross-linked structure) fundamentally alters the polymer's ability to stabilize rotigotine in an amorphous state, preventing crystallization while maintaining drug solubility and patch integrity.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If conventional adhesives like silicone-based or acrylic-based agents are used, then the patch can be manufactured, but rotigotine does not dissolve or precipitates over time reducing skin permeability

Engineering Contradiction:
Improvepatch manufacturingVSAvoidrotigotine dissolution and skin permeability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a composite adhesive system by combining a rubber-based adhesive base agent with cross-linked polyvinylpyrrolidone. This composite material integrates the adhesive properties needed for patch manufacturing with the stabilizing properties that prevent rotigotine precipitation. The synergistic combination ensures both ease of manufacture and reliable drug dissolution with maintained skin permeability.

Inventive Principle:
Principle #40Composite materials

3Stability of the object's composition

If antioxidants are used to prevent decomposition, then some stability is improved, but they do not adequately prevent crystal precipitation and reduce skin permeability

Engineering Contradiction:
Improvedecomposition preventionVSAvoidskin permeability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent uses cross-linked polyvinylpyrrolidone as an intermediary that addresses the limitations of antioxidants. While antioxidants prevent chemical decomposition, the cross-linked polymer provides an additional stabilization mechanism by preventing physical transformation from amorphous to crystalline form. This dual approach maintains both chemical stability and physical solubility, ensuring adequate skin permeability is preserved.

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The patch achieves high skin permeability and long-term stability of rotigotine, preventing crystallization and maintaining effective drug delivery.

Implementation Method 1

the adhesive agent layer contains rotigotine and/or a pharmaceutically acceptable salt thereof in a dissolved form, and further contains a styrene-based thermoplastic elastomer, a petroleum-based resin and/or a terpene-based resin, an aliphatic alcohol, and cross-linked polyvinylpyrrolidone

Methodology Applied
Scientific EffectCrystallization prevention: Crystallisation

Implementation Method 2

a rotigotine-containing patch comprising: a backing layer; and an adhesive agent layer, wherein the adhesive agent layer contains rotigotine and/or a pharmaceutically acceptable salt thereof in a dissolved form

Methodology Applied
Scientific EffectTransdermal permeation: Permeation

Data Source

PatentEP3730129B1Rotigotine-containing patch
Publication Date: 2024.08.07 HISAMITSU PHARM CO INC
  • EP3730129B1 patent drawingFigure 1
  • EP3730129B1 patent drawingFigure 2
  • EP3730129B1 patent drawingFigure 3

AI summary

The present invention provides a rotigotine-containing patch comprising: a backing layer; and an adhesive agent layer, wherein the adhesive agent layer contains rotigotine and/or a pharmaceutically acceptable salt thereof, the adhesive agent layer further contains a styrene-based thermoplastic elastomer, a petroleum-based resin and/or a terpene-based resin, an aliphatic alcohol, and a cross-linked polyvinylpyrrolidone, and in the adhesive agent layer, a mass ratio of a content of the rotigotine and/or the pharmaceutically acceptable salt thereof in terms of rotigotine free form and a content of the cross-linked polyvinylpyrrolidone (content of the rotigotine and/or the pharmaceutically acceptable salt thereof in terms of rotigotine free form : content of the cross-linked polyvinylpyrrolidone) is 10 : 3 to 1 : 3.