Fentanyl Patch Abuse Deterrence via Naloxone Cocrystals

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Solution Overview

Problem

Fentanyl transdermal patches are susceptible to misuse and abuse, leading to dangerous opioid overdose and addiction due to their rapid absorption and high potency, and existing solutions are complex and not fully effective in preventing or mitigating these issues.

Innovation Solution

A drug-in-adhesive transdermal patch containing fentanyl and a cocrystal of naloxone or naltrexone, which acts as an opioid antagonist, is developed to provide a tamper-resistant and abuse-deterrent formulation. The patch incorporates a cocrystal of naloxone or naltrexone in an adhesive polymer matrix, ensuring controlled release of the antagonist to block opioid effects during misuse or abuse, thereby reducing the euphoric effects and preventing overdose.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fentanyl transdermal patches are used for pain management, then therapeutic analgesic effect is achieved, but the patches are susceptible to misuse and abuse leading to overdose and addiction

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidmisuse and abuse susceptibility
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces an opioid antagonist (naloxone or naltrexone) as an intermediary substance co-formulated with fentanyl in the transdermal patch. This intermediary blocks the harmful effects of fentanyl when misused while allowing therapeutic effects during proper use, resolving the contradiction between therapeutic efficacy and abuse susceptibility

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical-chemical parameters of the antagonist by forming cocrystals with specific coformers (such as nicotinamide, isonicotinamide, or other aromatic carboxylic acids). This cocrystal formation modifies solubility, dissolution rate, and release characteristics of the antagonist, enabling controlled release that blocks opioid effects only during abuse scenarios while maintaining therapeutic equivalence during legitimate use

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If existing abuse-deterrent formulations are implemented, then misuse resistance is improved, but the formulations become complex and not fully effective

Engineering Contradiction:
Improveabuse resistanceVSAvoidformulation complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent combines the opioid agonist (fentanyl) and opioid antagonist (naloxone or naltrexone) into a single transdermal patch formulation with unified adhesive matrix and controlled release mechanism. This merging approach integrates multiple functions (analgesia + abuse deterrence) into one system, reducing complexity compared to multi-layer or multi-reservoir designs while maintaining effectiveness

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent employs cocrystal composite materials formed by the antagonist with specific coformers. These composite materials provide tailored release profiles and enhanced stability, achieving effective abuse deterrence through a single integrated formulation rather than complex multi-component systems

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP3352822B1Cocrystals of naloxone and naltrexone
Publication Date: 2022.07.27 PAIN THERAPEUTICS INC
  • EP3352822B1 patent drawingFigure 1~2
  • EP3352822B1 patent drawingFigure 3~4
  • EP3352822B1 patent drawingFigure 5~6

AI summary

This invention relates to cocrystals of naloxone and of naltrexone and thier use as opioid antagonists. The cocrystais of the invention include naloxone isonicotinamide cocrystal, naloxone hydrochloride piperazine cocrystal, naltrexone menthol cocrystal, naltrexone thymine cocrystal, naltrexone 2,5-dihydroxybenzoic acid cocrystal, naltrexone salicylic acid cocrystal, naltrexone hydrochloride piperazine cocrystal and naltrexone hydrochloride sulfathiazole cocrystal. A drug-in¬ adhesive transdermal patch con taining the opioid analgesic fentanyl or an analog thereof and a cocrystal of naloxone or naltrexone is disclosed. Also disclosed is a method of treating pain, such as acute, chronic or intermittent pain, by applying a drug-in-adhesive transdermal patch of the invention to the skin of a patient in need thereof. Also disclosed is an improved transdermal patch for administering fentanyl or an analog thereof, or for administering a mu opioid agonist, the improvement wherein the transdermal patch contains a cocrystal of the invention in an abuse limiting amount. The improved transdermal patch may be a drug-in-adhesive transdermal patch or a reservoir transdermal patch.