Enteric-Release Beads in Oral Films for Abuse-Resistant Opiate Delivery

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Solution Overview

Problem

Current pain management drugs, particularly opiates, are addictive and prone to misuse, and there is a need for longer-acting opioid formulations that effectively treat chronic or acute pain without inducing euphoria, while also preventing abuse.

Innovation Solution

Development of oral films with a controlled-release composition that includes a matrix polymer and enteric-release beads containing an opioid agonist and antagonist, designed for intestinal release, with a pH adjuster to bind the opioids to the polymer, providing a prolonged therapeutic effect and hindering misuse through buccal adhesion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If opiate analgesics are administered to treat severe pain, then pain relief is achieved, but addiction and euphoric side effects occur

Engineering Contradiction:
Improvepain relief effectivenessVSAvoidaddiction and euphoric side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent divides the opioid delivery system into multiple functional components: enteric-release beads containing the opioid agonist are dispersed within a matrix polymer, creating a segmented structure that enables controlled intestinal release. This segmentation allows the opioid to be delivered only to the intestine, bypassing the stomach and reducing euphoric effects while maintaining pain relief effectiveness.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary mechanism - the enteric-release polymer coating on the beads - that mediates between the opioid agonist and the body. This intermediary ensures the opioid is released only in the intestine at pH levels above 5.0, preventing premature release in the stomach that would cause euphoria and addiction, while still delivering the medication for pain relief.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Speed

If opioid agonist is released in the stomach, then rapid absorption occurs, but euphoric effects and abuse potential increase

Engineering Contradiction:
Improveabsorption speedVSAvoideuphoric effects and abuse potential
Core Design Contradiction:
SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent changes the release parameter of the opioid by using pH-sensitive enteric-release polymers that remain intact at stomach pH (below 5.0) but dissolve at intestinal pH (above 5.0). This parameter change ensures the opioid is released only in the intestine, maintaining controlled absorption speed while eliminating euphoric effects and reducing abuse potential.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If film is designed for buccal adhesion, then misuse is hindered, but manufacturing complexity increases

Engineering Contradiction:
Improveabuse preventionVSAvoidfilm structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses composite materials by combining the matrix polymer with enteric-release beads containing the opioid agonist. This composite structure provides both the buccal adhesion properties needed for misuse prevention and the controlled intestinal release mechanism, achieving abuse prevention without excessive manufacturing complexity.

Inventive Principle:
Principle #40Composite materials

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 oral films provide a bioequivalent effect to existing opioid products with extended pain relief, reducing the risk of abuse by incorporating naloxone as an antagonist, ensuring the opioid agonist is released in the intestines, thereby minimizing euphoric effects and promoting safer, longer-lasting pain management.

Implementation Method 1

The controlled-release composition further comprises a pH adjuster in an amount effective to adjust the composition to a pH of about 2.0 to 3.0 pH units below the pKa of the opioid agonist, antagonist and their respective salts to bind the opioid to the enteric-release polymer

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

The enteric-release beads are formed from an enteric-release-bead composition including at least one enteric-release polymer and an opioid agonist and an opioid antagonist and/or their respective salts encapsulated therein

Methodology Applied
Scientific EffectEncapsulation: Physical Containment

Data Source

PatentEP2836197B1Oral film containing opiate enteric-release beads
Publication Date: 2019.06.19 LTS LOHMANN THERAPIE SYST AG
  • EP2836197B1 patent drawingFigure 1

AI summary

A control release and abuse-resistant opiate drug delivery oral wafer or edible oral film dosage to treat pain and substance abuse is provided. The drug delivery oral wafer or edible oral film dosage includes a controlled release layer containing enteric-release beads dispersed in a polymer matrix. The enteric-release beads are formed from a therapeutic amount of an opioid agonist and/or pharmaceutically acceptable salt thereof and a sub- therapuetic amount of opioid antagonist and/or pharmaceutically acceptable salt thereof coated or encapsulated in an enteric-release polymer. The controlled release polymer matrix dissolves or disintegrates following administration or consumption of the oral wafer or edible oral film, releasing the enteric-release beads to be swallowed, with subsequent absorption of the active ingredients within the patient's intestines.