Esketamine Oral Mucosal Liquid Formulation with Cholic Acid
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Solution Overview
Problem
Existing esketamine formulations for nasal administration face challenges such as high concentration risks, nasal irritation, limited bioavailability, and potential for abuse, while nasal spray formulations do not meet the needs of patients with nasal inflammation or poor tolerance, and the volume is insufficient for therapeutic doses.
Innovation Solution
A liquid esketamine formulation for oral mucosa administration, comprising esketamine or a pharmaceutically acceptable salt, cholic acid or a derivative, and water, with optional additives like tackifiers and buffers, to enhance stability, absorption, and bioavailability, reducing irritation and abuse risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If nasal spray formulation is used to achieve therapeutic dose, then concentration of esketamine hydrochloride must be high, but this increases the risk of ketamine abuse
Solution Approach 1:
The patent changes the administration route from nasal to oral mucosal, which fundamentally alters the pharmacokinetic parameters. This allows achieving therapeutic doses with lower concentrations, thereby reducing abuse risk while maintaining efficacy
Solution Approach 2:
The patent introduces cholic acid or its derivative as a carrier substance that facilitates esketamine absorption through the oral mucosa. This intermediary mechanism enables effective drug delivery without requiring high concentrations, thus mitigating abuse potential
2Speed
If nasal spray formulation is used, then esketamine is absorbed quickly, but drug absorption in the body is not good and bioavailability is not high
Solution Approach 1:
Cholic acid or its derivative serves as an absorption promoter that enhances esketamine penetration through the oral mucosal barrier. This intermediary substance significantly improves bioavailability while maintaining rapid absorption characteristics
Solution Approach 2:
The patent modifies the administration route and formulation parameters to optimize both absorption speed and bioavailability. The oral mucosal route with cholic acid carrier achieves superior bioavailability compared to nasal spray while maintaining quick onset
3Reliability
If high concentration of esketamine hydrochloride is used in nasal spray, then therapeutic effect is achieved, but this increases the risk of ketamine abuse and causes nasal irritation
Solution Approach 1:
The patent fundamentally changes the concentration parameters by switching to oral mucosal administration. This allows achieving therapeutic effects at much lower concentrations, thereby eliminating nasal irritation and reducing abuse risk while maintaining efficacy
Solution Approach 2:
Cholic acid or its derivative acts as a carrier that enables effective drug delivery at low concentrations through the oral mucosa. This intermediary mechanism provides therapeutic effect without requiring high concentrations that cause irritation and 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 esketamine liquid formulation achieves rapid absorption, high bioavailability, and improved patient compliance with reduced side effects, suitable for treating major, unipolar, refractory, intractable, and bipolar depression.
Implementation Method 1
The formulation of the present application has high stability, rapid absorption, high bioavailability
Data Source
AI summary
An esketamine liquid preparation. The esketamine liquid preparation is an aqueous solution agent, comprising esketamine or a pharmaceutically acceptable salt thereof, cholic acid or a derivative thereof, and water, with a pH value of 2.5-5.7. The esketamine liquid preparation is administrated via oral mucosa, and the preparation is high in stability, fast in absorption, high in bioavailability, simple in administration mode, and good in compliance. The esketamine liquid preparation can be used for preventing, relieving, or treating major depression, unipolar depression, treatment-refractory depression, intractable depression, agitated depression, and bipolar depression.