Cyclodextrin-Enhanced Edaravone Liquid Composition for Oral Stability
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Solution Overview
Problem
Existing edaravone formulations face challenges with poor solubility and stability in aqueous solutions, leading to degradation and difficulty in oral administration for conditions like ALS, particularly for patients with dysphagia, necessitating a stable and ready-to-use oral solution with minimal excipients and improved patient compliance.
Innovation Solution
Development of stable liquid pharmaceutical compositions of edaravone comprising pharmaceutically acceptable solvents and excipients, such as solubility enhancers, antioxidants, and crystallization inhibitors, maintaining edaravone concentration between 0.05 mg/mL to 50 mg/mL and pH between 2.0 to 7.0, ensuring stability for at least 3 months under various storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If edaravone is formulated as an aqueous solution, then oral administration is facilitated, but solubility and stability are poor leading to rapid degradation
Solution Approach 1:
The patent uses cyclodextrins as intermediary molecules that form inclusion complexes with edaravone. The cyclodextrin's hydrophilic exterior and hydrophobic interior cavity accommodate the lipophilic edaravone molecule, thereby enhancing its aqueous solubility and stability without requiring extreme pH conditions or excessive excipients.
Solution Approach 2:
The patent modifies the molecular parameters of edaravone by forming a complex with cyclodextrin, changing its effective solubility characteristics. The complexation alters the hydrophobicity-hydrophilicity balance, enabling the drug to remain stable in aqueous solutions at physiological pH ranges (2.0-7.0) without rapid degradation.
2Quantity of substance
If edaravone is formulated as a suspension, then solubility issues are addressed, but sedimentation and caking occur reducing drug uniformity
Solution Approach 1:
Cyclodextrins act as mediators that keep edaravone molecules in solution through inclusion complex formation. This prevents the drug from precipitating or forming suspensions that would sediment and cake, thereby maintaining uniform drug distribution throughout the formulation storage period.
3Manufacturing precision
If edaravone is administered intravenously, then precise medication delivery is achieved, but patient compliance deteriorates due to frequent injections and hospital visits
Solution Approach 1:
The patent develops an oral formulation that enables patients to self-administer edaravone at home without requiring hospital visits or caregiver assistance. The stable aqueous solution with cyclodextrin allows for convenient oral dosing while maintaining precise medication delivery, thereby improving patient compliance and quality of life.
4Quantity of substance
If edaravone concentration is increased in oral solution, then treatment effectiveness is improved, but solubility limits are exceeded causing precipitation
Solution Approach 1:
Cyclodextrins serve as solubility-enhancing intermediaries that can accommodate higher concentrations of edaravone in aqueous solution. The inclusion complexes prevent precipitation even at elevated drug concentrations, allowing the formulation to achieve therapeutic effectiveness while maintaining physical stability.
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.