Single-layer oral dose of neuro-attenuating ketamine
Inventors
Nivorozhkin, Alex • Landrau, Nelson
Assignees
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Publication Number
US-11554100-B2
Publication Date
2023-01-17
Expiration Date
Abstract
The present invention is directed to oral neuro-attenuating ketamine (NAKET) tablet formulations, and methods of administration, which ensure the steady release of a therapeutically effective concentration of ketamine from an oral tablet without neurologically toxic spikes in ketamine concentration. In particular, the present invention provides single layer oral tablet formulation of NAKET. In a specific embodiment, the NAKET tablet formulation, and methods of administration provide steady administration of NAKET to a subject for 24 hours or greater, for example, up to 36 hours, after a single administration event.
Core Innovation
The invention relates to neuro-attenuating ketamine (NAKET) oral, single-layer tablet compositions and corresponding approaches for providing steady, continuous ketamine/norketamine exposure after a single administration. The objective is to maintain exposure without neurologically toxic concentration spikes, including psychotomimetic toxic spikes associated with ketamine.
The compositions include NAKET comprising a polymer and ketamine, or a pharmaceutically acceptable salt of ketamine, in a single-layer orally administered tablet. A key formulation concept is combining a water-insoluble, neutrally charged non-ionic matrix with a negatively charged-group polymer, with examples including polyacrylic acid types such as Carbopol 974 NF and alternative systems such as HPMC/starch, HPMC/carbopol, Kollidon SR, lipophilic matrices, and PEO/HPMC systems.
The patent also states pharmacokinetic targeting and supporting data directed to preventing concentration spikes while enabling sustained exposure. It describes targeting combined plasma ketamine and norketamine concentrations of about 10–500 ng/mL, maintaining these concentrations over a release period greater than 4 hours, and provides in vivo beagle dog data indicating steady release without detected spikes.
Claims Coverage
The document provides one independent claim directed to a single-layer oral tablet composition comprising NAKET, with the inventive features centered on the composition definition and pharmacokinetic and release-period constraints tied to maintaining combined ketamine and norketamine plasma concentrations while avoiding toxic spikes.
Single-layer orally administered tablet composition with neuro-attenuating ketamine
A single-layer orally administered tablet composition comprising neuro-attenuating ketamine (NAKET), the NAKET comprising a polymer and ketamine, or a pharmaceutically acceptable salt of ketamine.
Neuro-attenuating ketamine with combined plasma ketamine and norketamine concentration maintenance
The tablet composition has a combined plasma concentration of ketamine and its metabolite norketamine in the range of 10–500 ng/ml and maintains this concentration for the duration of the release period.
Neuro-attenuating ketamine release period greater than 4 hours
The tablet composition has a release period for the NAKET that is greater than 4 hours.
Therapeutically effective amount of ketamine for treating depression
The tablet composition includes an amount of ketamine therapeutically effective for treating depression.
Neuro-attenuating ketamine salt form selection
The pharmaceutically acceptable salt is a hydrochloride salt, aspartate salt, or succinate salt.
Water-insoluble neutrally charged non-ionic matrix with selected components
The non-ionic matrix is selected from cellulose-based polymers, alone or enhanced by mixing with components selected from starches, waxes, neutral gums, polymethacrylates, PVA, PVA/PVP blends, or mixtures thereof.
Overall, the claim set centers on a single-layer orally administered tablet containing neuro-attenuating ketamine where the NAKET comprises a polymer and ketamine, or a specified ketamine salt. The main inventive refinements define pharmacokinetic and release-period constraints by maintaining combined plasma ketamine and norketamine within about 10–500 ng/mL over the release period for more than 4 hours.
Stated Advantages
Provides steady, continuous ketamine/norketamine exposure after a single administration.
Avoids neurologically toxic concentration spikes, including psychotomimetic toxic spikes.
Enables sustained release without detected spikes in the described in vivo beagle dog data.
Documented Applications
Treatment contexts explicitly tied to dependent claims include depression.
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