Abuse-Deterrent Transdermal Patch with Antagonist Barrier Layer
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Solution Overview
Problem
Current opioid formulations, particularly buprenorphine, face challenges such as high abuse potential, variable blood-plasma concentration leading to adverse effects, and poor patient compliance due to sublingual administration, which also fails to effectively manage chronic pain and withdrawal symptoms.
Innovation Solution
Development of an abuse-resistant transdermal patch formulation comprising a backing layer, an opioid antagonist layer, a barrier layer with water-insoluble and water-soluble polymers, and an opioid agonist/antagonist layer, including buprenorphine prodrugs, to control release and prevent misuse.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If opioid agonists are administered via sublingual therapy, then pain relief and withdrawal symptom management are achieved, but patient compliance deteriorates and adverse effects increase
Solution Approach 1:
The patent replaces the sublingual administration route with transdermal delivery via a patch system. This substitution eliminates the need for sublingual placement and dissolution, improving patient compliance while maintaining therapeutic effectiveness through controlled release of opioid agonists into the bloodstream.
Solution Approach 2:
The patent changes the delivery parameter from intermittent sublingual dosing to continuous transdermal release. The patch delivers opioid agonists at controlled rates over extended periods, maintaining stable blood concentrations that reduce adverse effects while improving patient compliance through once-weekly application.
2Ease of operation
If extended release opioid products are used, then patient compliance improves, but abuse potential increases
Solution Approach 1:
The patent segments the opioid agonist delivery into controlled transdermal release portions and incorporates opioid antagonists in separate layers. This segmentation prevents illicit users from obtaining a bolus dose through misuse, as the antagonist layers will block euphoric effects if the patch is tampered with or removed and placed in solvent for injection.
Solution Approach 2:
The patent introduces opioid antagonist layers as an intermediary protective mechanism. These layers act as a deterrent by blocking the euphoric effects if abuse attempts occur, while not interfering with therapeutic delivery when the patch is used as intended. The barrier layer with controlled porosity also serves as an intermediary that regulates drug release.
3Speed
If rapid absorption is achieved, then immediate pain relief is provided, but euphoric effects and abuse potential increase
Solution Approach 1:
The patent employs periodic action through controlled transdermal release, delivering opioid agonists at steady, controlled rates rather than all at once. This periodic delivery maintains therapeutic blood concentrations without producing the rapid spike associated with euphoric effects and abuse potential.
4Ease of operation
If first-pass metabolism is present, then oral administration is simple, but therapeutic concentrations are reduced
Solution Approach 1:
The patent substitutes the oral administration route with transdermal delivery. This replacement bypasses the gastrointestinal tract and first-pass metabolism in the liver, allowing higher proportions of the administered opioid agonist to reach systemic circulation and achieve therapeutic concentrations.
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 transdermal patch provides sustained release, reduces abuse potential, minimizes adverse effects, and improves patient compliance by maintaining therapeutic concentrations while preventing euphoric effects upon misuse, effectively managing chronic pain and opioid dependence.
Implementation Method 1
a barrier layer located between the first and second layer, the barrier layer comprising: a water-insoluble polymeric material and a water-soluble polymer; wherein the release ratio is between about 1:60 and about 60:1 after the patch has been placed in ethanol, water or a phosphate buffer having a pH of about 6.5 for greater than about 30 seconds
Implementation Method 2
transdermal administration can provide a favorable route of administration. Transdermal dosing provides the patient with a desirable systemic delivery profile
Implementation Method 3
the opioid antagonist prodrug is a naltrexone prodrug which is a compound of Formula (X): wherein R 3 O is comprised of a bio-labile linker; or a pharmaceutically acceptable salt thereof
Data Source
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AI summary
Described herein are abuse-resistant multi-layer transdermal patches comprising opioids and opioid prodrugs having a barrier layer located between the layer containing opioid or opioid prodrug and a layer containing an opioid antagonist or opioid antagonist prodrug.