Memantine Derivatives Controlled Release via Phase Transition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Memantine, a drug used for neurodegenerative diseases and diabetes, has high water solubility and adverse effects such as confusion, dizziness, and hallucinations, limiting its therapeutic use.
Innovation Solution
Development of memantine derivatives with reduced solubility, formulated into microcrystalline or nanocrystalline suspensions to control drug release and minimize adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If memantine is used for therapeutic purposes, then therapeutic effects are achieved, but adverse effects such as confusion, dizziness, and hallucinations occur due to high water solubility and rapid release
Solution Approach 1:
The patent modifies the solubility parameter of memantine by creating derivatives with reduced water solubility. This parameter change transforms memantine from a highly water-soluble compound to one with controlled solubility, enabling sustained release and reducing peak concentration-related adverse effects while maintaining therapeutic efficacy.
Solution Approach 2:
The patent utilizes phase transition by formulating memantine derivatives as microcrystalline or nanocrystalline suspensions. This phase transition from dissolved to suspended state enables controlled release kinetics, preventing rapid absorption and associated adverse effects while maintaining therapeutic action.
2Ease of manufacture
If memantine is formulated with high water solubility, then ease of formulation is improved, but loss of substance occurs due to rapid release and reduced therapeutic window
Solution Approach 1:
The patent changes the solubility parameter by introducing hydrophobic substituents on the adamantane ring. This modification reduces water solubility while maintaining formulation feasibility through suspension technology, thereby preventing drug loss from rapid clearance and extending therapeutic action.
3Duration of action of moving object
If memantine derivatives with reduced solubility are developed, then duration of action is improved through controlled release, but device complexity increases due to derivative synthesis and formulation requirements
Solution Approach 1:
The patent employs phase transition to microcrystalline or nanocrystalline suspension form, which inherently provides controlled release kinetics. This approach extends duration of action without requiring complex delivery devices, as the suspension formulation itself enables sustained release through controlled dissolution and diffusion processes.
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 derivatives provide a controlled release of memantine, reducing adverse effects and improving therapeutic efficacy for neurodegenerative diseases and diabetes treatment.
Implementation Method 1
Due to the lower solubility, these derivatives can form a diffusion layer on the surface of the crystals, thus controlling the release of the drug
Implementation Method 2
formulated into a microcrystalline or nanocrystalline suspension
Data Source
AI summary
Provided are compounds of formula (I), or a stereoisomer, mixture of stereoisomers, deuterated analog, tautomer, solvate or pharmaceutically acceptable salt thereof, compositions, method of making and uses thereof.