Dexamethasone Eye Drop Composition for pH Stability During Storage

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Solution Overview

Problem

Cyclodextrin-based eye drops containing dexamethasone experience pH instability during storage, leading to drug oxidation and degradation, which hampers effective ocular treatment.

Innovation Solution

The addition of additives such as sodium thiosulfate, methionine, 3,4-dihydroxybenzoic acid, sodium citrate, malic acid, sodium ascorbate, tartaric acid, α-monothioglycerol, butylated hydroxyanisole, lauryl gallate, lactic acid, or tert-butylhydroquinone, or their salts or derivatives, at concentrations between 0.15% and 0.6% (w/v), stabilizes the pH of the aqueous composition by preventing drug oxidation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If cyclodextrin-based eye drops containing dexamethasone are stored in LDPE vials, then the formulation is convenient for ocular administration, but the pH decreases over time and the drug oxidizes

Engineering Contradiction:
Improveconvenience of ocular administrationVSAvoidpH stability during storage
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

An antioxidant additive is introduced as an intermediary substance to prevent the harmful interaction between the drug and oxygen during storage. The antioxidant acts as a mediator that sacrifices itself to protect the dexamethasone from oxidation, thereby maintaining pH stability without affecting the convenience of eye drop administration

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The antioxidant is added in advance to the formulation before storage, performing a preliminary protective action. This preliminary action prevents oxidation from occurring during the storage period, ensuring pH stability is maintained throughout the shelf life without requiring any changes to the administration process

Inventive Principle:
Principle #10Preliminary action

2Duration of action of stationary object

If cyclodextrin-based eye drops are stored for several months, then the formulation has sufficient shelf life for distribution, but the pH decreases and drug oxidation occurs

Engineering Contradiction:
Improveshelf life during storageVSAvoiddrug stability during storage
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The antioxidant serves as a protective intermediary that extends the reliable storage period. By introducing this intermediary substance, the formulation can be stored for several months with maintained drug stability, as the antioxidant prevents oxidation reactions that would otherwise compromise reliability over time

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The chemical composition parameter of the formulation is changed by adding the antioxidant additive. This parameter change transforms the formulation from one that is unstable during long-term storage to one that maintains reliable drug stability throughout the intended shelf life

Inventive Principle:
Principle #35Parameter changes

3Device complexity

If no antioxidant is added to the formulation, then the formulation remains simple and cost-effective, but the drug oxidizes and pH decreases during storage

Engineering Contradiction:
Improveformulation simplicityVSAvoiddrug stability during storage
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The antioxidant is used as a sacrificial, low-cost component that protects the valuable drug. This inexpensive additive is consumed over time during storage, providing reliable drug stability without significantly increasing formulation complexity or cost

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 method effectively maintains the pH of the aqueous composition comprising dexamethasone and gamma-cyclodextrin for over six months, ensuring the drug's stability and efficacy during storage.

Implementation Method 1

the pH of cyclodextrin-based eye drops with active principle ingredient is not stable and decreases overtime... addition of an additive to prevent oxidation of the drug

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

addition of an additive selected from the group consisting of sodium thiosulfate, methionine, 3,4-dihydroxybenzoic acid, sodium citrate, malic acid, sodium ascorbate, tartaric acid, α-monothioglycerol, butylated hyroxyanisole, lauryl gallate, lactic acid, tert-butylhydroquinone, and their salts or derivatives, or mixtures thereof to prevent oxidation of the corticosteroid

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentEP3993807B1Method for stabilizing the ph of an aqueous composition comprising a drug
Publication Date: 2025.12.17 OCULIS OPERATIONS SARL

AI summary

The present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a drug which is prone to oxidation, said method comprising the addition of an additive to prevent oxidation of the drug which is prone to oxidation. In particular, the present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a corticosteroid, said method comprising the addition of an additive to prevent oxidation of the corticosteroid. The present disclosure also relates to a composition comprising a corticosteroid and an additive to prevent oxidation of the corticosteroid.