Extended-Release Ketamine Matrix Without PEO Abuse Deterrent
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Solution Overview
Problem
Existing pharmaceutical compositions, such as ketamine formulations, face abuse deterrent challenges due to unintended administration routes, leading to adverse effects, and there is a need for a composition that provides equivalent pharmacokinetics without using polyethylene oxide (PEO).
Innovation Solution
An extended release pharmaceutical composition incorporating ketamine or norketamine into a sustained-release polymeric matrix with a matrix polymer and permeability-modifying filler, avoiding PEO.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high-molecular weight polyethylene oxide (PEO) is used as an abuse deterrent formulation, then the product becomes more difficult to crush and dissolve, but it causes unexpected harmful effects such as thrombotic thrombocytopenic purpura (TTP) and renal failure with thrombotic microangiopathy (TMA)
Solution Approach 1:
The patent removes PEO from the formulation entirely and replaces it with alternative polymers (carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose) that provide sustained release without causing TTP or TMA. This extraction of the harmful substance while maintaining the desired abuse deterrent effect directly resolves the contradiction.
Solution Approach 2:
The patent changes the polymer type parameter from PEO to cellulose-based polymers, altering the chemical composition while maintaining the physical property of sustained release. This parameter change eliminates the harmful effects associated with PEO while preserving the abuse deterrent functionality.
2Duration of action of moving object
If PEO is used to create extended release formulation, then the release profile shows critical advantages for treatment-resistant depression, but undissolved particles of PEO in injected solution cause fatal bleeding disorder and renal failure
Solution Approach 1:
The patent extracts PEO from the formulation and substitutes it with cellulose-based polymers that provide equivalent extended release pharmacokinetics without forming undissolved particles that cause fatal adverse effects. The alternative polymers maintain the desired duration of action while eliminating the harmful particle formation.
Solution Approach 2:
The patent uses polymers that are more readily biodegradable and less likely to persist as undissolved particles in the body. The cellulose-based polymers are naturally more compatible with biological systems and less likely to cause the fatal effects associated with PEO persistence.
3Reliability
If ketamine is formulated for medicinal purposes, then it provides therapeutic benefits for depression and pain, but it can be abused via alternative administration routes such as crushing, dissolving, and injecting
Solution Approach 1:
The patent removes the possibility of abuse by extracting the ability to crush and dissolve the medication. The sustained-release matrix formulation physically prevents crushing and dissolution, eliminating the routes of abuse while maintaining therapeutic effectiveness through controlled release.
Solution Approach 2:
The patent uses a composite material system consisting of ketamine combined with sustained-release polymers (carboxymethylcellulose, hydroxypropylcellulose, or hydroxypropylmethylcellulose). This composite structure provides both therapeutic benefit and abuse deterrent properties, as the polymer matrix controls release and prevents manipulation for abuse.
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 composition achieves sustained release kinetics similar to PEO-based formulations, reducing abuse potential and minimizing adverse effects while effectively managing depression, anxiety, and pain.
Implementation Method 1
a permeability-modifying filler
Data Source
AI summary
Described is an extended release pharmaceutical composition. The composition comprises a therapeutically effective amount of an active agent selected from the group consisting of ketamine, norketamine, pharmaceutically acceptable salts thereof, and combinations thereof. The active agent is incorporated into a sustained-release polymeric matrix. The matrix comprises a matrix polymer, and a permeability-modifying filler. A method of preventing, treating and/or managing treatment-resistant depression in a subject is also or alternatively describe.