Multi-Layered Extended Release Matrix Formulation

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Solution Overview

Problem

Current controlled release opioid analgesic formulations are susceptible to tampering, crushing, and alcohol exposure, leading to unintended rapid drug release, and lack resistance to zero-order release profiles.

Innovation Solution

A solid oral extended release pharmaceutical dosage form featuring a multi-layered extended release matrix formulation with high molecular weight polyethylene oxide layers, providing a zero-order release rate and resistance to tampering, crushing, and alcohol extraction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional controlled release formulations are used, then the active agent is released over an extended period, but the formulations are susceptible to tampering, crushing, and alcohol exposure leading to rapid drug release

Engineering Contradiction:

Improverelease durationVSAvoidresistance to tampering

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The dosage form is divided into multiple layers with distinct functions: an outer alcohol-resistant layer containing polyethylene glycol and an inner active agent-containing layer. This segmentation allows the outer layer to protect against alcohol extraction while the inner layer maintains controlled release properties, resolving the contradiction between extended release duration and resistance to tampering.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The formulation uses a composite structure combining polyethylene glycol (alcohol-resistant material) with polyethylene oxide and active agent in separate layers. This composite approach allows the alcohol-resistant outer layer to prevent tampering while the inner layer ensures prolonged controlled release, addressing both reliability and duration requirements simultaneously.

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If the formulation is designed for zero-order release, then plasma levels are maintained in therapeutic range, but the formulation remains vulnerable to crushing and extraction

Engineering Contradiction:

Improveplasma level stabilityVSAvoidsusceptibility to crushing

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The outer alcohol-resistant layer containing polyethylene glycol is applied in advance to prevent harmful actions such as alcohol extraction and crushing before they can affect the inner active agent layer. This preliminary protective barrier maintains plasma level stability by preventing premature drug release even when the dosage form is subjected to mechanical or chemical stress.

Inventive Principle:

Principle #9Preliminary anti-action

3Adaptability or versatility

If the formulation allows alcohol extraction, then the active agent can be liberated for immediate release, but this creates a risk of dose dumping when patients use alcohol with the dosage form

Engineering Contradiction:

Improveresponse to alcohol exposureVSAvoiddose dumping risk

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The formulation converts the potentially harmful effect of alcohol exposure into a beneficial protective mechanism. The outer layer containing polyethylene glycol is specifically designed to resist alcohol extraction, thereby preventing dose dumping. What could have been a harmful interaction (alcohol causing rapid release) is transformed into a protected state where the alcohol-resistant layer blocks the harmful extraction process while allowing the intended controlled release to proceed.

Inventive Principle:

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

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 formulation ensures a consistent and prolonged release of the active agent, maintaining therapeutic plasma levels and preventing unintended rapid drug release, even when exposed to alcohol or subjected to mechanical stress.

Implementation Method 1

a first composition forming a first active agent containing layer of the extended release matrix formulation comprising: (a) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000; and (b) at least one active agent

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

extended release matrix formulation comprising (1) a first composition forming a first active agent containing layer of the extended release matrix formulation

Methodology Applied

Scientific EffectErosion:

Implementation Method 3

a second composition forming an active agent-free second layer of the extended release matrix formulation comprising at least one polyethylene oxide

Methodology Applied

Scientific EffectPhysical barrier:

Data Source

PatentEP2688556B1Controlled release pharmaceutical dosage forms

Publication Date: 2015.05.06 PURDUE PHARMA LP

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AI summary

The present invention relates to pharmaceutical multilayer dosage forms, for example to a tamper resistant dosage form comprising a first layer comprising an active agent and a second layer not comprising said active agent, and processes of manufacture, uses, and methods of treatment thereof providing essentially zero order release.