Sequestered Opioid Antagonist in Extruded Dosage Form
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Solution Overview
Problem
There is a need for an oral dosage form of opioid agonists that reduces abuse potential without affecting analgesic efficacy or causing withdrawal, and which remains effective when administered intact but releases an opioid antagonist to prevent abuse upon tampering.
Innovation Solution
A pharmaceutical oral dosage form comprising extruded particles with an opioid antagonist dispersed in a hydrophobic matrix and coated with a hydrophobic layer, designed to prevent the release of the antagonist when the dosage form is administered intact but releases it upon tampering, thereby blocking the opioid agonist's effect.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If an opioid antagonist is combined with an opioid agonist to deter parenteral abuse, then the abuse potential is reduced, but the antagonist may be released during normal administration causing withdrawal or affecting analgesic efficacy
Solution Approach 1:
The opioid antagonist is encapsulated within a sequestration matrix that is itself embedded in the dosage form. This nested structure ensures the antagonist remains isolated and non-releasable during normal administration, while becoming available only when the dosage form is tampered with and the nested structure is compromised.
Solution Approach 2:
The patent creates distinct regions with different properties: a sequestration matrix that prevents antagonist release under normal conditions, and a tamper-responsive region that releases the antagonist when mechanical or chemical tampering occurs. This local differentiation allows the same formulation to have opposing release behaviors under different conditions.
2Reliability
If the opioid antagonist is made readily available to block abuse, then abuse potential is reduced, but the analgesic efficacy of the opioid agonist is compromised during normal use
Solution Approach 1:
The dosage form is designed with preliminary sequestration of the antagonist in a controlled matrix structure. This preliminary arrangement ensures that the antagonist remains inactive and sequestered during normal administration, allowing full analgesic efficacy, while being pre-positioned to become active only upon tampering detection.
3Duration of action of moving object
If a controlled release formulation is used to maintain steady opioid levels, then analgesic efficacy is improved, but the formulation can be crushed to provide immediate release for abuse
Solution Approach 1:
The patent incorporates a preliminary anti-action mechanism where the sequestered antagonist is positioned to counteract any attempt at abuse. When the controlled-release formulation is crushed or tampered with, the antagonist is released to block the opioid agonist's effects, thereby preventing the harmful consequence of immediate release abuse while maintaining normal controlled-release analgesia.
4Reliability
If an opioid antagonist is included in the dosage form, then abuse potential is reduced, but the complexity of the formulation increases
Solution Approach 1:
The patent merges the sequestration function and the abuse-deterrence function into a single integrated dosage form structure. The sequestration matrix serves dual purposes: maintaining the controlled-release profile for therapeutic efficacy and simultaneously sequestering the antagonist to prevent premature release. This merging reduces overall formulation complexity compared to separate systems.
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 dosage form effectively reduces the potential for abuse by ensuring the opioid antagonist is not released during normal administration, while significantly increasing its release upon tampering, thereby blocking the opioid agonist's effect and preventing misuse.
Implementation Method 1
an opioid antagonist dispersed in a hydrophobic matrix and coated with a hydrophobic layer, designed to prevent the release of the antagonist when the dosage form is administered intact
Implementation Method 2
releases it upon tampering, thereby blocking the opioid agonist's effect
Data Source
AI summary
Disclosed in certain embodiments is a dosage form comprising a plurality of extruded particles comprising an adverse agent or antagonist and a layer disposed about the particles.