Transdermal System Using Solid Urea for Permeation

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Solution Overview

Problem

Transdermal therapeutic systems face challenges in delivering active pharmaceutical ingredients with high daily dosages through the skin due to limited skin permeability, often requiring auxiliary measures that compromise skin tolerance.

Innovation Solution

Incorporating solid urea in a coarse-grained form, with a weight proportion of at least 20% in the layer facing the skin, to enhance skin permeability of active substances, particularly in transdermal therapeutic systems with a polyacrylate or polymethacrylate matrix, where urea constitutes 20-60% by weight with particle sizes greater than 50 μm.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If auxiliary measures such as permeation-promoting substances, electrical voltage, or microlesions are applied to increase active ingredient flow through the skin, then the permeation of active substances is improved, but skin tolerance deteriorates

Engineering Contradiction:
Improvepermeation of active substancesVSAvoidskin tolerance
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical state parameter of urea from dissolved/liquid form to solid crystalline form with specific particle sizes (50-100 μm). This parameter change allows urea to function as a permeation enhancer without the harmful effects associated with conventional liquid permeation promoters, thereby improving active substance permeation while maintaining skin tolerance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite adhesive layer combining polyacrylate or polymethacrylate matrix with solid urea particles. This composite material integrates the adhesive functionality with the permeation-enhancing property of urea, achieving both skin adhesion and enhanced drug delivery without compromising skin compatibility.

Inventive Principle:
Principle #40Composite materials

2Productivity

If high proportions of dissolved or liquid urea are used as permeation promoter, then skin permeability is improved, but skin compatibility deteriorates due to excessive moisture and potential irritation

Engineering Contradiction:
Improveskin permeabilityVSAvoidskin compatibility
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent transforms urea from dissolved/liquid state to solid crystalline state with controlled particle size (50-100 μm). This parameter change eliminates the moisture-related harmful effects of liquid urea while preserving its permeation-enhancing capability, thus improving skin permeability without compromising skin compatibility.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses solid urea particles that are incorporated into the adhesive layer and gradually released during the transdermal delivery process. These particles serve as temporary permeation enhancers that fulfill their function and are eventually depleted, providing effective permeation promotion without long-term skin irritation.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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

Significantly increases the permeation of active substances by a factor of 4 to 9, as demonstrated in in vitro tests, while maintaining good skin compatibility, particularly for muscle relaxants, antihypertensives, psychostimulants, and antiemetics, with urea's coarse-grained particles exceeding 100 μm in size.

Implementation Method 1

Incorporating solid urea in a coarse-grained form, with a weight proportion of at least 20% in the layer facing the skin, to enhance skin permeability of active substances

Methodology Applied
Scientific EffectPermeation enhancement: Permeation

Data Source

PatentEP2234605B1Transdermal therapeutic system having urea components
Publication Date: 2015.08.05 LTS LOHMANN THERAPIE SYST AG
  • EP2234605B1 patent drawingFigure 1
  • EP2234605B1 patent drawingFigure 2
  • EP2234605B1 patent drawingFigure 3

AI summary

The invention relates to a transdermal therapeutic system (TTS) for administering pharmaceutical agents through the skin, comprising a back layer (R) impermeable to the agent and at least one layer (S) comprising the agent, wherein the layer (H) facing the skin comprises urea in solid form, allowing continuous administration of large quantities of agent over a long period of time.