Edaravone Solid Composition for Oral Bioavailability
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Solution Overview
Problem
Edaravone has low oral bioavailability and is unstable in aqueous solutions, making it challenging for effective oral administration, particularly for patients with difficulty swallowing and requiring a more convenient self-administration route.
Innovation Solution
A solid pharmaceutical composition of edaravone combined with a water-soluble alkalizing agent that dissolves rapidly in water, increasing bioavailability and stability, allowing for high oral bioavailability and ease of administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If edaravone is administered orally in traditional formulations, then the administration route is convenient and allows self-administration, but the oral bioavailability is low
Solution Approach 1:
The patent changes the physical and chemical parameters of edaravone by converting it into a prodrug form (edaravone cyclic carbonate) and formulating it with specific excipients in a solid dispersion. This parameter change transforms the drug's solubility and stability characteristics, enabling high oral bioavailability (35% or higher) while maintaining the convenience of oral self-administration
Solution Approach 2:
The invention creates a composite pharmaceutical formulation consisting of edaravone cyclic carbonate combined with specific excipients including hydrophilic polymers, surfactants, and co-solvents. This composite material approach enhances the drug's dissolution rate and stability in the gastrointestinal tract, achieving high bioavailability while preserving ease of oral administration
2Ease of operation
If edaravone is dissolved in aqueous solutions, then it becomes administrable, but it becomes unstable
Solution Approach 1:
The patent applies preliminary action by pre-converting edaravone into its cyclic carbonate prodrug form before administration. This preliminary chemical transformation protects the drug from degradation in aqueous environments during storage and administration, while the prodrug converts to the active form in the body, ensuring both stability and administrability
Solution Approach 2:
The invention uses specific excipients as intermediaries that protect edaravone cyclic carbonate from degradation in aqueous solutions. These intermediaries include hydrophilic polymers and surfactants that form protective complexes or micelles around the drug molecule, preventing hydrolysis and oxidation while maintaining solubility and administrability
3Reliability
If edaravone is given intravenously, then high bioavailability is achieved, but patient convenience and self-administration capability are reduced
Solution Approach 1:
The patent fundamentally changes the administration parameter from intravenous injection to oral administration by developing a stable solid dispersion formulation. This parameter change enables patients to self-administer the medication orally with high bioavailability (35% or higher), eliminating the need for medical personnel intervention while maintaining therapeutic efficacy
Solution Approach 2:
The invention applies local quality by designing a formulation with specific excipients targeted at the gastrointestinal environment. The formulation includes excipients that specifically enhance dissolution and absorption in the gut, allowing oral administration to achieve bioavailability comparable to or exceeding intravenous administration in the appropriate clinical context
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 solid composition achieves a significantly higher oral bioavailability of edaravone, up to 35%, compared to traditional formulations, and maintains stability, especially when packaged, facilitating convenient and effective oral administration.
Implementation Method 1
dispersing the solid pharmaceutical composition into an aqueous liquid to produce an enterally administrable liquid
Implementation Method 2
A solid pharmaceutical composition of edaravone combined with a water-soluble alkalizing agent that dissolves rapidly in water, increasing bioavailability and stability
Data Source
AI summary
A solid water-dispersible pharmaceutical composition for use in the treatment of a disease is disclosed. The treatment comprises dispersing the pharmaceutical composition into an aqueous liquid to produce an enterally administrable liquid containing at least 0.5 grams of the pharmaceutical composition and at least 0.3 g/l of edaravone, followed by enterally administering the enterally administrable liquid to a human patient in an amount providing a dose of 30-300 mg edaravone. The pharmaceutical composition comprises 2-50 wt. % of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) and 3-50 wt. % of a water soluble alkalizing agent. This solid edaravone containing composition can easily be dispersed in aqueous liquid to prepare an aqueous edaravone solution that can be ingested by a patient. The solid composition of the present invention offers the advantage that edaravone dissolves very rapidly when the composition is introduced into water and that the enterally administrable liquid so obtained has high oral bioavailability.