Liquid Edaravone Composition for Stable Enteral Administration
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Solution Overview
Problem
Current edaravone formulations face challenges with poor solubility and stability in aqueous solutions, leading to degradation and difficulty in oral administration for patients with dysphagia, necessitating a stable, ready-to-use liquid formulation suitable for enteral administration.
Innovation Solution
Development of stable liquid pharmaceutical compositions of edaravone comprising pharmaceutically acceptable solvents and excipients, including solubility enhancers, antioxidants, and crystallization inhibitors, maintaining stability at various storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If edaravone is formulated as an aqueous solution, then it provides ease of administration and patient compliance, but it exhibits poor stability and rapid degradation
Solution Approach 1:
The patent introduces cyclodextrins as intermediary molecules that form inclusion complexes with edaravone. The cyclodextrin cavity accommodates the edaravone molecule, protecting it from degradation while maintaining solubility in aqueous media. This mediator approach resolves the contradiction by enabling both aqueous formulation and stability simultaneously.
Solution Approach 2:
The patent creates a composite system consisting of edaravone-cyclodextrin inclusion complexes combined with antioxidants and other excipients. This composite formulation provides enhanced stability through multiple protective mechanisms while maintaining the liquid oral suspension form for ease of administration.
2Stability of the object's composition
If edaravone is formulated as a solid form, then it provides long-term stability, but it is not user-friendly for patients with dysphagia
Solution Approach 1:
The patent changes the physical state parameter from solid to liquid by formulating edaravone as an oral suspension. The inclusion complexes with cyclodextrins enable the drug to be dispersed in liquid medium while maintaining stability, thus transforming the formulation from solid to liquid form suitable for dysphagic patients.
3Ease of operation
If edaravone is formulated as an oral suspension, then it improves patient compliance, but it suffers from sedimentation, caking, and poor re-dispersibility
Solution Approach 1:
Cyclodextrins act as mediators that prevent particle aggregation and sedimentation by forming stable inclusion complexes. The hydrophilic exterior of cyclodextrins maintains dispersion in aqueous medium, while the hydrophobic cavity protects edaravone molecules, preventing caking and ensuring uniform re-dispersibility.
Solution Approach 2:
The patent modifies the molecular organization parameter by forming inclusion complexes, which change the physical behavior of edaravone in suspension. This prevents the formation of large aggregates that would sediment and cake, maintaining reliable dosage uniformity throughout the shelf life.
4Measurement precision
If edaravone is administered intravenously, then it provides precise and comprehensive medication delivery, but it requires frequent injections and hospital visits
Solution Approach 1:
The patent replaces the parenteral (intravenous) administration route with an oral route. The inclusion complex formulation enables oral bioavailability by protecting edaravone from degradation in the gastrointestinal tract, substituting the mechanical injection system with an oral dosage system that eliminates hospital visits while maintaining therapeutic efficacy.
Data Source
AI summary
The present invention relates to liquid pharmaceutical compositions of edaravone. More specifically, stable solutions of edaravone for enteral administration are provided, wherein the composition is stable for extended period of time. The present invention further relates to stable solutions of edaravone, methods for their administration, processes for their production, and use of these compositions for treatment of diseases treatable by edaravone.