8-oxo-2'-deoxyguanosine Eye Drop Formulation Stability

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Solution Overview

Problem

The low water solubility of 8-oxo-2'-deoxyguanosine and its precipitation issues in aqueous solutions make it difficult to develop a stable eye drop formulation for corneal injuries, and significant drug leakage occurs during repeated instillations, leading to ineffective retention in the eye.

Innovation Solution

An eye drop formulation with a viscosity of 10 to 30 mPa·s, comprising 8-oxo-2'-deoxyguanosine or its pharmaceutically acceptable salt, combined with polyvinylpyrrolidone, hydroxypropyl methylcellulose, polyethylene glycol, and polysorbate, which functions as a thickening, stabilizing, and solubilizing agent, preventing precipitation and ensuring long-term stability and retention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If the compound of Formula 1 is solubilized by heating a mixture containing the compound in aqueous solution, then the compound can be dissolved in water, but when the aqueous solution is stored at room temperature, the compound precipitates

Engineering Contradiction:

Improvesolubility of 8-oxo-2'-deoxyguanosineVSAvoidstability of aqueous solution at room temperature

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent introduces a solubilizing agent as an intermediary substance that facilitates the dissolution of 8-oxo-2'-deoxyguanosine in water without requiring heating. The solubilizing agent forms a complex or micellar structure that keeps the compound dissolved at room temperature, preventing precipitation while maintaining stability during storage.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical environment parameters by adjusting pH, ionic strength, or adding specific excipients that alter the solubility characteristics of 8-oxo-2'-deoxyguanosine. This allows the compound to remain dissolved at room temperature without heating, resolving the contradiction between solubility and stability.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If the pH of a mixture containing the compound of Formula 1 is increased to solubilize it, then the compound can be dissolved, but the compound cannot be solubilized in the pH range suitable for eye drop formulation (pH 5 to 7)

Engineering Contradiction:

Improvesolubility of 8-oxo-2'-deoxyguanosineVSAvoidpH compatibility for eye drop formulation

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent introduces a solubilizing agent as a mediator that enables dissolution within the physiologically acceptable pH range of 5-7. This intermediary substance allows the compound to solubilize without requiring extreme pH conditions, making the formulation compatible with eye drop requirements.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite formulation system where 8-oxo-2'-deoxyguanosine is combined with solubilizing agents, buffering agents, and other excipients to form a stable aqueous solution. This composite approach allows solubilization within the narrow pH window suitable for ophthalmic use.

Inventive Principle:

Principle #40Composite materials

3Productivity

If an eye drop formulation is prepared for repeated instillations, then effective treatment can be achieved, but a significant amount of the drug solution leaks from the eye

Engineering Contradiction:

Improveefficacy of repeated instillationsVSAvoidleakage of eye drop formulation

Core Design Contradiction:

ProductivityVSLoss of substance

Solution Approach 1:

The patent modifies the rheological parameters of the eye drop formulation by adjusting viscosity through the selection and concentration of solubilizing agents and thickening agents. This parameter change increases the formulation's retention time on the ocular surface, reducing leakage while maintaining comfort and efficacy for repeated instillations.

Inventive Principle:

Principle #35Parameter changes

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 formulation maintains stability and suitable retention in the eye for extended periods, preventing precipitation and allowing for effective long-term and repeated administrations without leakage, even at room temperature for up to 12 months.

Implementation Method 1

an eye drop formulation in the form of an aqueous solution having a certain viscosity (i.e., a viscosity of 10 to 30 mPa s)

Methodology Applied

Scientific EffectViscosity:

Implementation Method 2

a stable eye drop that does not show precipitation under a room temperature condition for 12 months

Methodology Applied

Scientific EffectSolubilization: Solvation

Data Source

PatentEP4523679A1Eye drop formulations in the form of an aqueous solution comprising 8-oxo-2'-deoxyguanosine or a pharmaceutically acceptable salt thereof

Publication Date: 2025.03.19 RUDACURE CORP

AI summary

The present invention provides an eye drop formulation in the form of an aqueous solution, comprising 8-oxo-2'-deoxyguanosine or a pharmaceutically acceptable salt thereof; a thickening agent; a buffering agent; and a chelating agent, in an aqueous medium, wherein the eye drop formulation has a viscosity of 10 to 30 mPa·s. The eye drop formulation of the present invention exhibits suitable retention time in the eye as well as excellent stability without precipitation even when stored for a long period of time.