Oxycodone Aryl Carboxylic Acid Conjugates for Abuse Deterrence
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Solution Overview
Problem
Current opioid formulations, such as those containing oxycodone, face challenges in preventing abuse due to their potential for rapid release and euphoric effects, leading to addiction, and existing abuse-deterrent technologies have not effectively addressed these issues.
Innovation Solution
The development of oxycodone conjugates with aryl carboxylic acids, which require enzymatic or metabolic breakdown for release, providing a slow and sustained delivery through oral administration while resisting abuse via intravenous or intranasal routes, thereby reducing addiction potential and side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional opioid formulations are used, then pain relief is achieved, but abuse potential and addiction risk increase due to rapid release and euphoric effects
Solution Approach 1:
The oxycodone molecule is chemically conjugated with aryl carboxylic acid moieties, segmenting the drug into a composite structure where the active opioid is bound to aromatic acid groups. This segmentation prevents free oxycodone from rapidly binding to opioid receptors, thereby reducing euphoric effects and abuse potential while maintaining therapeutic pain relief through controlled enzymatic release
Solution Approach 2:
The patent creates composite molecular structures by covalently bonding oxycodone to aryl carboxylic acids, forming hybrid molecules that combine the analgesic properties of oxycodone with the structural characteristics of aromatic acids. This composite approach modifies the drug's pharmacokinetic profile to provide sustained release while deterring abuse
2Object-affected harmful factors
If extended release formulations are used, then abuse deterrence is improved, but illicit users attempt to circumvent by injecting or tampering with dosage forms
Solution Approach 1:
The patent fundamentally changes the chemical parameter of oxycodone by conjugating it with aryl carboxylic acids, transforming it from a readily absorbable opioid into a prodrug requiring metabolic activation. This parameter change ensures that even if the dosage form is tampered with or injected, the conjugated structure prevents rapid release of active oxycodone, maintaining abuse deterrence across multiple administration routes
3Object-affected harmful factors
If oxycodone is conjugated with aryl carboxylic acids, then abuse potential is reduced through slow release, but manufacturing complexity increases
Solution Approach 1:
The patent employs coupling agents as intermediary substances to facilitate the conjugation between oxycodone and aryl carboxylic acids. These intermediaries enable the formation of stable amide or ester bonds between the opioid and aromatic acid moieties, simplifying the manufacturing process by providing reliable, standardized reaction protocols for creating the abuse-deterrent conjugates
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 oxycodone conjugates offer a therapeutic equivalent AUC with reduced peak plasma concentrations, decreased variability, and resistance to physical or chemical manipulation, effectively deterring abuse and minimizing side effects like constipation.
Implementation Method 1
requiring the active oxycodone to be released through enzymatic or metabolic breakdown of the conjugate in vivo
Implementation Method 2
requiring the active oxycodone to be released through enzymatic or metabolic breakdown of the conjugate in vivo
Data Source
AI summary
The presently described technology provides compositions comprising aryl carboxylic acids and, for example NSAIDs, chemically conjugated to oxycodone (4,5-α-epoxy-14-hydroxy-17-methylmorphinan-6-one) to form novel prodrugs/compositions of oxycodone, including benzoates, salicylates, propionates, fenamates, and acetates, which have a decreased potential for abuse of oxycodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.