Ketamine Transdermal Patch Matrix for High Early Flux Stability

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Solution Overview

Problem

Transdermal therapeutic systems for ketamine face challenges in achieving optimal flux and stability of the active ingredient, particularly in the first 2 to 12 hours after application, while maintaining chemical and physical stability, and require a simpler design for economic production.

Innovation Solution

A transdermal therapeutic system comprising a backing layer and a matrix layer with a pressure-sensitive adhesive containing free hydroxyl groups, such as acrylic copolymers like 2-ethylhexyl acrylic acetate and vinyl acetate, and a penetration enhancer mixture of levulinic acid and methyl laurate, ensuring high flux and optimal utilization of (S)-ketamine without crystallization inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If a transdermal therapeutic system is worn for several days, then the cumulative dose delivery is improved, but the risk of bacterial contamination and infection increases

Engineering Contradiction:
Improvewearing durationVSAvoidbacterial contamination
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by incorporating a kill switch mechanism that is pre-programmed to stop drug delivery at a predetermined time. This prevents prolonged wear and potential bacterial contamination while ensuring the system is discontinued before infection risk becomes significant. The kill switch is set during manufacturing to activate automatically after a specific duration.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback through a microprocessor-controlled system that monitors the operational status and can terminate drug delivery based on predetermined criteria. The system provides feedback about the cumulative dose delivered and can automatically stop operation when the predetermined time is reached, preventing excessive wear and associated contamination risks.

Inventive Principle:
Principle #23Feedback

2Manufacturing precision

If the transdermal therapeutic system is made programmable with a microprocessor, then the precision of dose delivery is improved, but the device complexity increases

Engineering Contradiction:
Improvedose delivery precisionVSAvoidsystem complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the control system into distinct functional modules: a microprocessor unit for intelligent control, a separate power source, a drug reservoir, and a kill switch mechanism. This modular segmentation allows precise dose delivery through the microprocessor while managing complexity by organizing functions into independent, manageable components.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements multi-functionality by designing the microprocessor to perform multiple functions: controlling drug delivery timing, monitoring cumulative dose, managing the kill switch activation, and potentially adjusting delivery rates. This universal control element reduces the need for separate dedicated components for each function, managing overall system complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Reliability

If the transdermal therapeutic system delivers a cumulative dose over several days, then the therapeutic effectiveness is improved, but the risk of unintended overdose increases

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidunintended overdose
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-programming the kill switch with a predetermined time limit and cumulative dose threshold before the system is activated. This ensures that the system will automatically stop drug delivery before an unintended overdose can occur, while still allowing sufficient wear time to achieve therapeutic effectiveness.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback through continuous monitoring of the cumulative dose delivered and comparison against predetermined safety thresholds. The microprocessor tracks the total amount of drug delivered and can activate the kill switch if the threshold is approached, preventing unintended overdose while maintaining therapeutic effectiveness through controlled cumulative delivery.

Inventive Principle:
Principle #23Feedback

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 system achieves a higher flux and optimal utilization of (S)-ketamine, maintaining chemical stability and physical stability, with improved skin tolerance and economic production, while avoiding the need for crystallization inhibitors.

Implementation Method 1

a battery, which delivers a pulsating electrical current

Methodology Applied
Scientific EffectBattery (electricity): Battery (electricity)

Implementation Method 2

The controller is adapted to control the parameters of the pulsating current, in particular the frequency, the voltage and/or the intensity of the pulsating current delivered by the battery

Methodology Applied
Scientific EffectElectroporation:

Data Source

PatentEP3955901B1Transdermal therapeutic system
Publication Date: 2026.05.06 LTS LOHMANN THERAPIE SYST AG
  • EP3955901B1 patent drawingFigure 1
  • EP3955901B1 patent drawingFigure 2
  • EP3955901B1 patent drawingFigure 3

AI summary

The present invention concerns a transdermal therapeutic system, comprising a backing layer, which is not permeable for the active ingredient, and a matrix layer on one side of the backing layer, wherein the matrix layer contains at least one pressure sensitive adhesive and ketamine or a pharmaceutically acceptable salt or solvate thereof, wherein the at least one pressure sensitive adhesive has free hydroxyl groups, as well as its use as medicament, in particular for the treatment of depression and pain.