Tapentadol Abuse-Deterrent Matrix via Hot Melt Extrusion

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Solution Overview

Problem

Current oral formulations of Tapentadol for severe chronic pain lack abuse-proof features while providing controlled release, which is essential for preventing misuse and ensuring patient compliance.

Innovation Solution

A sustained release and abuse-proof composition of Tapentadol is developed using hot melt extrusion with hydrophilic and hydrophobic polymers, combined with viscosity-enhancing agents, resulting in tablets with a hardness above 500N and increased viscosity when diluted, making them difficult to administer parenterally, nasally, or orally for abuse.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If Tapentadol is formulated as immediate release, then the drug can be easily administered and absorbed, but the frequency of administration increases and patient compliance decreases

Engineering Contradiction:
Improveease of administrationVSAvoidpatient compliance
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The patent applies dynamic release characteristics by formulating Tapentadol in a matrix system that provides sustained release over time. The composition transitions from immediate release to controlled sustained release, maintaining therapeutic levels while reducing administration frequency to once or twice daily, thereby improving patient compliance without compromising ease of administration

Inventive Principle:
Principle #15Dynamics

2Productivity

If Tapentadol is formulated for sustained release, then administration frequency is reduced and patient compliance increases, but the formulation becomes more complex

Engineering Contradiction:
Improvepatient complianceVSAvoidformulation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs composite materials by combining Tapentadol with polymer matrices and other excipients to create a sustained release formulation. This composite approach enables controlled drug release while maintaining a manageable formulation structure that can be manufactured using conventional pharmaceutical techniques, balancing compliance improvement with formulation complexity

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent utilizes parameter changes by modifying the physical and chemical properties of the formulation components, such as polymer molecular weight, crosslinking degree, and drug-polymer ratio. These parameter adjustments control the release kinetics of Tapentadol, achieving sustained release profiles without requiring overly complex formulation designs

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If Tapentadol is made available for abuse, then users can extract and administer it parenterally, but this creates safety risks and reduces therapeutic value

Engineering Contradiction:
Improvedrug availabilityVSAvoidabuse potential
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potential harm of abuse into a benefit by incorporating abuse-deterrent mechanisms into the sustained release formulation. The matrix structure and viscosity-enhancing properties prevent extraction and parenteral administration, while the same features ensure controlled therapeutic release. This transforms the formulation's resistance to manipulation from a limitation into a safety feature that deters abuse

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

4Object-affected harmful factors

If the formulation is made abuse-proof with high hardness, then it resists grinding and extraction, but manufacturing complexity increases

Engineering Contradiction:
Improveabuse resistanceVSAvoidmanufacturing ease
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by optimizing compression force, matrix composition, and viscosity-enhancing agent concentrations to achieve tablet hardness above 500N. These parameter adjustments enhance abuse resistance while maintaining compatibility with conventional tablet manufacturing processes, ensuring that the increased hardness does not prohibitively increase manufacturing complexity

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 composition achieves a drug release profile of over 80% after 12 hours and effectively prevents abuse by maintaining tablet integrity and forming a cohesive, insoluble gel when exposed to water, making intravenous administration unsafe.

Implementation Method 1

embedding the pharmacologically active ingredient in a matrix

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

embedding the pharmacologically active ingredient in a matrix

Methodology Applied
Scientific EffectErosion:

Implementation Method 3

forming a cohesive, insoluble gel when exposed to water

Methodology Applied
Scientific EffectGel formation: Gel

Implementation Method 4

hot melt extrusion with hydrophilic and hydrophobic polymers

Methodology Applied
Scientific EffectMelting: Melting

Data Source

PatentEP3946276B1Sustained release composition comprising tapentadol and method of preparation thereof
Publication Date: 2023.12.13 PHARMATHEN SA

AI summary

The present invention relates to a sustained release and abuse proof composition comprising Tapentadol or a pharmaceutically acceptable salt thereof for oral administration for the treatment of severe chronic pain in adults.