Fentanyl Matrix Transdermal Patch Using Carboxyl-Free Polyacrylate

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Solution Overview

Problem

Reservoir transdermal therapeutic systems (TTS) containing fentanyl and its analogs pose a safety risk due to the potential for excessive absorption in case of a leak, leading to fatal overdoses, as the active compound can be absorbed over a wide area of the skin.

Innovation Solution

A matrix system where fentanyl is incorporated directly into a self-adhesive polyacrylate, ensuring the active compound remains molecularly dispersed and is not absorbed in excess, even in case of damage, using polyacrylate adhesives without free carboxyl groups and solubility-reducing additives to control permeation rates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a reservoir system is used to contain fentanyl, then the active compound can be delivered effectively, but in case of a leak the active compound comes in contact with the skin over a wide area leading to excessive absorption and fatal overdoses

Engineering Contradiction:
Improvesafety against inadvertent absorptionVSAvoidexcessive absorption of active compound
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The reservoir system is segmented into multiple impermeable layers (sachet formed from an impermeable film as back layer and an active compound-permeable membrane) to contain the active compound. This segmentation prevents the active compound from contacting the skin over a wide area even if a leak occurs, as each layer acts as a barrier to contain the liquid or gelatinous preparation.

Inventive Principle:
Principle #1Segmentation

2Productivity

If the active compound is dissolved in a mixture of ethanol and water in a reservoir system, then effective delivery is achieved, but the system poses a safety risk in case of leakage

Engineering Contradiction:
Improveefficacious delivery of active compoundVSAvoidsafety against overdose
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system incorporates multiple impermeable layers and a membrane as beforehand cushioning measures to prevent the active compound from contacting the skin in case of leakage. This prior protection ensures that even if the reservoir is damaged, the active compound cannot be absorbed in excessively high doses, thereby cushioning against the harmful effects of potential overdose.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Reliability

If a matrix system with polyacrylate adhesive is used, then safety against excessive absorption is improved, but the adhesive must be specifically formulated without free carboxyl groups to achieve proper permeation rates

Engineering Contradiction:
Improvesafety against excessive absorptionVSAvoidspecific adhesive formulation requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The adhesive formulation parameters are specifically changed to exclude free carboxyl groups, which would increase the saturation solubility of fentanyl above the preferred range. By controlling the chemical composition parameters of the polyacrylate adhesive (using esters of acrylic and/or methacrylic acid without free functional groups), the system achieves both safety against excessive absorption and proper permeation rates.

Inventive Principle:
Principle #35Parameter changes

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 matrix system provides increased safety by limiting the absorption area and achieving effective permeation rates while preventing excessive active compound absorption, resulting in a safer and more controlled release of fentanyl and its analogs.

Implementation Method 1

the active compound is generally completely, but to at least 80%, dissolved in molecularly disperse form in this polymer, the saturation solubility of the active compound in the polymer being between 3 and 20% by weight

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

a control membrane and thus the active compound flow through the skin is restricted to a maximum value independently of the individual skin condition

Methodology Applied
Scientific EffectPermeation: Permeation

Implementation Method 3

only adhesives without free carboxyl groups are suitable... ensuring the active compound remains molecularly dispersed and is not absorbed in excess

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS10568845B2Transdermal therapeutic system with fentanyl or related substances
Publication Date: 2020.02.25 LTS LOHMANN THERAPIE SYST AG

AI summary

The invention relates to a transdermal therapeutic system (TTS), comprising a backing layer, which is permeable to the active ingredient, at least one matrix layer, comprising fentanyl or an active agent analogous to fentanyl, based on polyacrylate and a protective layer to be removed before usage, characterized in that the polyacrylate polymer is self-adhesive, free of carboxyl groups, has a saturation solubility for fentanyl of 3 to 20 wt. %, preferably of 4 to 12 and particularly of 5 to 10 wt. % and the layers contain at least 80% of the included active ingredient in a molecularly-dispersed, dissolved form.