Tamper-Resistant Opioid Multiparticulates via Ion Interaction
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Solution Overview
Problem
Current pharmaceutical compositions of opioid analgesics, such as oxycodone and morphine, are vulnerable to abuse due to their ability to be crushed and dissolved for rapid bioavailability, leading to misuse and diversion, despite existing tamper-resistant features which may cause adverse effects in legitimate patients.
Innovation Solution
Development of abuse-deterrent pharmaceutical compositions in the form of multiparticulates with modified lipophilic or water-insoluble materials, formulated using processes like spray congealing, which slow down drug release even when the physical integrity is compromised, utilizing excipients that interact ionically with the drug to enhance lipophilicity and reduce solubility, and coated with water-insoluble layers to prevent easy extraction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If traditional sustained release formulations are used, then therapeutic efficacy is maintained over extended time, but the formulations become vulnerable to abuse through crushing and grinding
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by incorporating aversive agents (bittering agents, irritants, or toxic substances) that activate upon tampering. This modifies the release characteristics - legitimate oral administration maintains sustained release over 6-24 hours, while crushing or grinding triggers immediate release of the aversive agent, creating a harmful effect that deters abuse
Solution Approach 2:
The patent converts potentially harmful substances (aversive agents) into a protective mechanism. These agents are incorporated into the sustained release formulation in a way that they remain dormant during legitimate use but become harmful if the formulation is crushed or ground, thereby converting a harm (toxicity) into a benefit (abuse deterrence)
2Object-affected harmful factors
If aversive agents are added to deter abuse, then abuse potential is reduced, but adverse effects occur in legitimate patients
Solution Approach 1:
The patent applies local quality by creating spatial and temporal differentiation in the formulation's properties. The aversive agent is distributed throughout the matrix but remains localized within the sustained release structure during legitimate use. Only when the formulation is physically compromised (crushed/grinded) does the aversive agent become exposed and active, creating a localized harmful effect at the site of tampering while leaving legitimate patients unaffected
3Speed
If sustained release action is destroyed by crushing, then rapid bioavailability occurs leading to high doses, but simple tampering methods provide no deterrent
Solution Approach 1:
The patent applies preliminary anti-action by pre-incorporating aversive agents into the sustained release formulation that will counteract any attempt at abuse. Before the abuser can exploit the rapid release of high doses through crushing, the aversive agent is already positioned to be released simultaneously, creating a preliminary protective action that prevents the harmful effect from occurring
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 compositions effectively deter improper administration by slowing down drug release, maintaining therapeutic efficacy over 6-24 hours while minimizing abuse potential without using aversive agents, and are less susceptible to tampering, ensuring safe and controlled delivery.
Implementation Method 1
formulated with one or more excipients that interact ionically with the drug to obtain a more lipopholic drug derivative
Implementation Method 2
excipients that interact ionically with the drug to enhance lipophilicity and reduce solubility
Implementation Method 3
coated with water-insoluble layers to prevent easy extraction
Implementation Method 4
formulated using processes like spray congealing
Implementation Method 5
spray congealing, which slow down drug release
Data Source
AI summary
Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.