Stable Edaravone Liquid Composition for Enteral Administration
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Solution Overview
Problem
Current edaravone formulations, particularly in liquid form, face challenges due to low aqueous solubility and stability issues, which hinder effective oral administration, especially for patients with dysphagia. Additionally, existing solutions may contain sulfite ions, causing allergic reactions and requiring warning statements on labeling.
Innovation Solution
Development of a stable, ready-to-use liquid pharmaceutical composition of edaravone suitable for enteral administration, comprising a solvent and excipients such as solubility enhancers, antioxidants, and crystallization inhibitors, which maintains edaravone in a solubilized state for an extended period without significant loss of potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If edaravone is formulated as an aqueous liquid solution, then oral administration becomes feasible, but stability deteriorates due to rapid degradation in aqueous solutions
Solution Approach 1:
The patent uses solubility enhancers and stabilizers as intermediary substances to enable edaravone to be formulated in liquid form while preventing degradation. These excipients mediate between the conflicting requirements of solubility and stability, allowing the drug to remain in solution without rapidly degrading.
Solution Approach 2:
The patent employs pH adjustment and control as a key parameter change strategy. By optimizing the pH of the aqueous solution and using pH-buffering excipients, the formulation maintains edaravone in a stable ionization state that prevents degradation while remaining soluble for oral administration.
2Quantity of substance
If edaravone is formulated as a suspension, then solubility issues are addressed, but drug uniformity deteriorates due to sedimentation and poor re-dispersibility
Solution Approach 1:
The patent introduces solubility enhancers and suspending agents as intermediary substances that allow edaravone to remain uniformly dispersed in liquid form. These excipients prevent sedimentation and ensure consistent drug distribution throughout the formulation, maintaining both solubility and uniformity.
Solution Approach 2:
The patent creates a composite liquid formulation combining edaravone with multiple excipients including solubility enhancers, suspending agents, and stabilizers. This composite system achieves both adequate solubility and uniform drug distribution, eliminating the problems of simple suspensions.
3Ease of operation
If conventional liquid formulations are used, then administration convenience is improved, but harmful factors increase due to sulfite ions causing allergic reactions
Solution Approach 1:
The patent explicitly excludes sulfite ions and other harmful excipients from the formulation. By removing these problematic substances while maintaining liquid formulation benefits, the patent achieves convenient administration without the risk of sulfite-induced allergic reactions.
Solution Approach 2:
The patent employs alternative excipients that are safer and more compatible with edaravone stability. These substitute substances provide the necessary formulation functions without the harmful side effects of conventional excipients like sulfites.
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 proposed solution achieves prolonged room temperature solubility and stability, enhancing patient compliance and ensuring effective treatment of amyotrophic lateral sclerosis (ALS) through improved bioavailability and reduced risk of allergic reactions.
Implementation Method 1
The edaravone anion becomes an edaravone radical when the anion donates an electron to oxygen. Thus, the electron reduction by the edaravone anion is the key step in edaravone degradation.
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.