Diquafosol Eye Drop Stabilization with Chelating Agent
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Solution Overview
Problem
Diquafosol ophthalmic solutions experience instability due to the formation of insoluble precipitates during storage, leading to filtration sterilization efficiency issues and eye irritation, and require enhanced preservative effectiveness.
Innovation Solution
Incorporating a chelating agent at a concentration of 0.0001 to 1% (w/v), such as edetic acid or its salts, into the ophthalmic solution to inhibit precipitate formation, reduce eye irritation, and enhance preservative effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If an aqueous ophthalmic solution containing diquafosol is stored, then the solution provides therapeutic benefit, but insoluble precipitates form during storage reducing stability
Solution Approach 1:
A chelating agent is introduced as an intermediary substance that binds to metal ions in the solution, preventing these ions from interacting with diquafosol to form precipitates. The chelating agent acts as a mediator that eliminates the harmful interaction between metal ions and the active ingredient, thereby preventing precipitate formation and maintaining solution stability during storage.
Solution Approach 2:
The invention changes the chemical environment of the solution by adding a chelating agent, which alters the availability and reactivity of metal ions in the solution. This parameter change in the chemical composition prevents the formation of insoluble compounds while maintaining the therapeutic efficacy of diquafosol.
2Stability of the object's composition
If the ophthalmic solution is filtered to remove precipitates, then solution stability is improved, but filtration sterilization efficiency deteriorates due to filter clogging
Solution Approach 1:
The chelating agent is added to the solution in advance to prevent precipitate formation before filtration is required. By taking preliminary action to stabilize the solution composition and prevent precipitate formation, the need for extensive filtration is eliminated, thereby maintaining high filtration sterilization efficiency without compromising solution stability.
3Duration of action of stationary object
If the ophthalmic solution is stored for distribution, then therapeutic availability is improved, but eye irritation increases due to precipitate formation
Solution Approach 1:
The chelating agent serves as a protective intermediary that remains in the solution during storage, continuously binding metal ions and preventing precipitate formation. This ensures that even after prolonged storage and distribution, the solution remains clear and free of precipitates that could cause eye irritation upon administration.
4Reliability
If preservative concentration is increased to enhance effectiveness, then preservative effectiveness is improved, but eye irritation increases
Solution Approach 1:
The invention converts the potential harm of metal ions (which cause precipitate formation) into a benefit by using the chelating agent to bind these ions. This eliminates the need for high concentrations of preservatives, as the chelating agent itself prevents precipitate formation and the associated eye irritation, thereby maintaining preservative effectiveness without increasing irritation.
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 addition of a chelating agent stabilizes the ophthalmic solution, prevents precipitate formation, improves filtration efficiency, reduces eye irritation, and enhances preservative effectiveness, resulting in a more stable and effective ophthalmic solution with reduced production costs.
Implementation Method 1
addition of a chelating agent at a concentration of 0.0001 to 1% (w/v) can inhibit formation of the insoluble precipitates
Data Source
Figure 1~2
AI summary
Regarding Diquafosol ophthalmic solution comprising a chelating agent at a concentration of 0.0001 to 1% (w/v), formation of insoluble precipitates found in Diquafosol ophthalmic solution during storage of the solution, as well as deterioration of the filtration performance in the course of production (course of filtration sterilization), have been inhibited. Further, in Diquafosol ophthalmic solution comprising a chelating agent, reduction of eye irritation and enhancement of the preservative effectiveness have been confirmed, in comparison to Diquafosol ophthalmic solution comprising no chelating agent. Accordingly, the present invention has been confirmed to provide physicochemical properties that are stable during the courses of production and distribution as well as the course of storage by a patient, and also reduce eye irritation and enhance preservative effectiveness. In particular, since degradation of the filtration performance in the course of production (course of filtration sterilization) is inhibited, Diquafosol ophthalmic solution comprising a chelating agent can be subjected to efficient filtration sterilization in the course of production, thereby contributing to a decrease in production cost.