Modified-Release Norketamine Formulations for Stable Plasma Levels
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current ketamine formulations face challenges with short therapeutic windows and neurologically toxic plasma concentration spikes, limiting their effectiveness and safety in oral administration for conditions like pain, depression, and neurological disorders.
Innovation Solution
Development of novel, isotopically-enriched, neuro-attenuating norketamine compounds formulated into oral and parenteral pharmaceutical compositions for controlled release, ensuring steady therapeutic levels without neurotoxic spikes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral ketamine is administered to achieve therapeutic effect, then pain and depression symptoms are alleviated, but neurologically toxic plasma concentration spikes occur causing sedation, hallucination, dizziness, and nausea
Solution Approach 1:
The patent changes the release rate parameter of ketamine from rapid (causing spikes) to controlled and sustained (maintaining therapeutic levels). This is achieved through modified-release tablet formulations that control the release kinetics of ketamine, preventing toxic concentration spikes while maintaining therapeutic effectiveness throughout the dosing interval.
Solution Approach 2:
The patent implements continuous therapeutic action by designing modified-release formulations that maintain steady ketamine plasma concentrations over extended periods (12-48 hours). This continuous release mechanism eliminates the peaks and troughs associated with conventional dosing, providing sustained pain relief and depression treatment without neurotoxic spikes.
2Reliability
If multiple daily doses of ketamine are administered to maintain therapeutic effect, then therapeutic window is extended, but patient compliance is reduced due to frequent dosing requirements
Solution Approach 1:
The patent extends the duration of therapeutic action from hours to 12-48 hours through modified-release formulations. This continuous action over extended periods eliminates the need for multiple daily doses, significantly improving patient compliance while maintaining reliable therapeutic effect throughout the dosing interval.
Solution Approach 2:
The patent dynamically adjusts the release rate of ketamine to match the body's metabolic clearance characteristics. The modified-release formulations are designed to release ketamine at rates that maintain steady plasma concentrations, automatically adapting to individual patient needs without requiring frequent dose adjustments or multiple daily administrations.
3Reliability
If ketamine infusion is used to achieve stable plasma levels and eliminate neurotoxic spikes, then therapeutic index is optimized, but the procedure becomes difficult to administer outside ICU settings and increases cost
Solution Approach 1:
The patent introduces modified-release tablet formulations as an intermediary that bridges the gap between IV infusion and oral dosing. These formulations replicate the steady plasma level profile achieved through infusion but in an oral format that can be administered in outpatient settings, eliminating the need for complex infusion equipment and specialized monitoring while maintaining optimized therapeutic indices.
Data Source
AI summary
The present invention is directed to novel neuro-attentuating norketamine (NANKET) compounds according to any one of formulas (I—shown below), (I-A) and (I-B), or any of the compounds described in Tables A-D, or in any of the Examples provided herein, and pharmaceutically acceptable salts thereof, novel pharmaceutical formulations and novel methods of uses thereof. The present invention also features novel oral neuro-attenuating ketamine (NAKET) and neuro-attenuating norketamine (NANKET) modified-release pharmaceutical formulations, and novel methods of administration thereof, which ensure the steady release of a therapeutically effective amount of ketamine, norketamine, or derivatives thereof from the oral modified-release pharmaceutical formulations without neurologically toxic spikes in plasma concentration of the ketamine, norketamine, or derivatives during the release periods.