Vitamin A Ophthalmic Composition Stabilization

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Solution Overview

Problem

Existing ophthalmic compositions containing high concentrations of vitamin A face stability challenges due to vitamin A's instability in aqueous solutions, which is not adequately addressed by previous stabilization methods.

Innovation Solution

Formulating an ophthalmic composition with at least 0.4 W/V % of polyoxyethylene polyoxypropylene glycol and trometamol, along with vitamin A, to enhance the stability of vitamin A, even at concentrations of 50,000 units/100 mL or higher.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If vitamin A is formulated at high concentration (≥50,000 units/100 mL) in aqueous ophthalmic composition, then therapeutic effectiveness is improved, but stability deteriorates due to oxidation and degradation

Engineering Contradiction:
Improvevitamin A concentrationVSAvoidvitamin A stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent introduces polyoxyethylene polyoxypropylene glycol as an intermediary substance that forms a protective complex with vitamin A, shielding it from oxidative degradation. This nonionic surfactant acts as a mediator between vitamin A and the aqueous environment, preventing direct contact with oxygen and other degrading factors while maintaining high vitamin A concentration in the formulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite stabilization system combining multiple components: polyoxyethylene polyoxypropylene glycol as the primary stabilizer, additional antioxidants (vitamin E, dibutylhydroxytoluene) as secondary protectors, and trometamol as a pH buffer. This multi-component composite approach provides synergistic protection against various degradation pathways including oxidation, hydrolysis, and pH-dependent degradation.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If conventional stabilization methods (nonionic surfactants, vitamin E) are used, then some stability is improved, but stability at high concentration (≥50,000 units/100 mL) remains insufficient

Engineering Contradiction:
Improvevitamin A stabilityVSAvoidvitamin A concentration
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent optimizes specific formulation parameters including the concentration of polyoxyethylene polyoxypropylene glycol (0.01-5% w/v), pH range (5.0-8.0 using trometamol buffer), and ratios of stabilizing components. By carefully controlling these parameters, the formulation achieves enhanced stability that allows vitamin A to be maintained at high concentrations without excessive degradation, overcoming the limitations of conventional stabilization methods.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high concentration of vitamin A is formulated, then therapeutic effect for corneal and conjunctival disorders is enhanced, but eye irritation increases

Engineering Contradiction:
Improvevitamin A concentrationVSAvoideye irritation
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The polyoxyethylene polyoxypropylene glycol serves as a protective intermediary that solubilizes high concentrations of vitamin A in the aqueous formulation, preventing direct contact between the lipophilic vitamin and ocular tissues. This mediator reduces irritation while maintaining therapeutic efficacy by controlling the release and distribution of vitamin A in the eye.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 composition effectively stabilizes vitamin A, providing improved storage stability and reducing eye irritation, while maintaining its therapeutic effects for corneal and conjunctival disorders and dry eye treatment.

Implementation Method 1

when at least 0.4 W/V % of polyoxyethylene polyoxypropylene glycol and trometamol are formulated in an ophthalmic composition containing at least 50,000 units/100 mL of vitamin A, the stability of vitamin A can be significantly enhanced

Methodology Applied
Scientific EffectSurfactant stabilization: Surfactant

Implementation Method 2

vitamin A that is a lipophilic vitamin is very sensitive to air, light, heat, acids, metal ions and the like

Methodology Applied
Scientific EffectBuffering action:

Data Source

PatentUS9012503B2Ophthalmic composition
Publication Date: 2015.04.21 LION CORP

AI summary

Disclosed is an ophthalmic composition containing (A) not less than 50,000 units/100 mL of vitamin A, (B) not less than 0.4 W/V % of a polyoxyethylene polyoxypropylene glycol, and (C) trometamol.