Extended Release Ketamine Tablet Using PEO Matrix

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Solution Overview

Problem

Current treatments for treatment-resistant depression, anxiety disorders, and phobias often involve invasive administration methods like injections, which can cause dissociative side effects and are time-consuming, and there is a need for an oral formulation that provides a prolonged release profile to minimize these side effects and improve patient compliance.

Innovation Solution

Development of an extended-release oral ketamine tablet using a hydrophilic polyethylene oxide matrix, which includes a core with a therapeutically effective amount of ketamine or norketamine and a coating that provides a crush-resistant formulation with a prolonged release profile, reducing dissociative side effects and allowing for once or twice-daily administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If injected ketamine is used to treat treatment-resistant depression and anxiety disorders, then rapid onset antidepressant effects are achieved, but dissociative side effects and increased blood pressure and heart rate occur

Engineering Contradiction:

Improveonset of antidepressant effectVSAvoiddissociative side effects

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent segments the rapid delivery of ketamine into a prolonged release profile by using a hydrophilic polymeric matrix (polyethylene oxide) that controls the dissolution rate. This segmentation of drug delivery over time maintains therapeutic efficacy while avoiding peak concentrations that cause dissociative side effects.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the release parameter of ketamine from immediate (injection) to extended (oral tablet with controlled dissolution). By modifying the formulation parameters including using high molecular weight PEO and specific ketamine salts, the drug achieves sustained release over 10-12 hours, reducing peak plasma concentrations and associated side effects.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If injected ketamine is administered, then antidepressant effects are achieved, but administration is time-consuming and onerous

Engineering Contradiction:

Improveantidepressant efficacyVSAvoidadministration convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical injection system with an oral tablet delivery system. This substitution eliminates the need for invasive procedures, needles, and clinical administration, allowing patients to self-administer the medication conveniently while maintaining therapeutic efficacy through controlled release.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Ease of operation

If oral ketamine formulation is developed, then administration convenience is improved, but rapid absorption may cause dissociative symptoms

Engineering Contradiction:

Improveadministration convenienceVSAvoiddissociative symptoms

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a hydrophilic polymeric matrix (polyethylene oxide) as an intermediary between the ketamine drug and the gastrointestinal environment. This matrix acts as a controlled-release vehicle that modulates the dissolution and absorption rate of ketamine, preventing rapid absorption while maintaining oral administration convenience.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Object-affected harmful factors

If extended release profile is implemented, then dissociative side effects are minimized, but formulation complexity increases

Engineering Contradiction:

Improvedissociative side effectsVSAvoidformulation complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies local quality by using a specific high molecular weight range of polyethylene oxide (2-7 million) that provides the desired controlled release properties. This targeted selection of material properties achieves extended release without requiring complex multi-component systems or sophisticated release mechanisms.

Inventive Principle:

Principle #3Local quality

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 extended-release oral ketamine tablet effectively treats treatment-resistant depression, anxiety disorders, and phobias with minimal dissociative side effects, providing sustained relief for several days and improving patient compliance through a convenient oral administration route.

Implementation Method 1

using a hydrophilic polymeric matrix approach. Polyethylene oxide (PEO) is one of a number of hydrophilic polymers used in controlled drug delivery formulations

Methodology Applied

Scientific EffectHydrophilic polymeric matrix dissolution: Solvation

Implementation Method 2

at least one high molecular weight polyethylene oxide (PEO) that is cured, wherein said high molecular weight PEO has an approximate molecular weight of from about 2 million to about 7 million

Methodology Applied

Scientific EffectCuring:

Implementation Method 3

a coating on said core, wherein said tablet is crush resistant and has a breaking strength of at least about 200 N

Methodology Applied

Scientific EffectCoating: Coatings

Data Source

PatentUS11471416B2Extended release pharmaceutical formulation and methods of treatment

Publication Date: 2022.10.18 DOUGLAS PHARMA

AI summary

The invention provides an oral extended release formulation for the treatment of treatment-resistant depression, treatment-resistant anxiety, and phobia.