Diclofenac Emulsified Gel Stability via Nonionic Polymer

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Solution Overview

Problem

Diclofenac sodium exhibits low stability in emulsified gel compositions, leading to decomposition products formation during storage, which affects the efficacy and shelf life of transdermal formulations.

Innovation Solution

An emulsified gel composition comprising diclofenac sodium, water, a nonionic water-soluble polymer gelling agent like hydrophobically-modified hydroxypropyl methyl cellulose, an antioxidant, and a surfactant with an HLB of 14 or more, with minimal ionic polymer content, which enhances stability and skin application feel.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If an emulsified gel composition is formulated with diclofenac sodium, then use feeling at the time of and after application onto the skin is improved, but drug stability of diclofenac sodium deteriorates

Engineering Contradiction:
Improveuse feelingVSAvoiddrug stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameters by selecting specific nonionic water-soluble polymers (hydroxypropyl cellulose or hydrophobically-modified hydroxypropyl methyl cellulose) as gelling agents and specifying surfactants with HLB values of 14 or more. This parameter optimization resolves the contradiction by creating an emulsified gel system that simultaneously provides excellent use feeling and maintains diclofenac sodium stability above 98% after 1 month at 60°C storage.

Inventive Principle:
Principle #35Parameter changes

2Strength

If ionic polymer is added to emulsified gel composition, then gel structure is enhanced, but drug stability decreases

Engineering Contradiction:
Improvegel structureVSAvoiddrug stability
Core Design Contradiction:
StrengthVSStability of the object's composition

Solution Approach 1:

The patent extracts or removes ionic polymers from the formulation entirely, or limits them to 0.5% by mass or less based on the mass of the whole emulsified gel composition. This elimination of the harmful component (ionic polymer) resolves the contradiction by preventing drug stability deterioration while maintaining adequate gel structure through alternative nonionic polymer systems.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces nonionic water-soluble polymers as intermediary substances that can provide the necessary gel structure and stability without causing drug decomposition. These nonionic polymers act as mediators that fulfill the structural requirement while being compatible with diclofenac sodium stability, unlike ionic polymers.

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 maintains 98% or more diclofenac sodium stability after 1 month at 60°C, improving drug stability and skin application characteristics, such as reduced stickiness and improved spreadability.

Implementation Method 1

a gelling agent, and wherein the gelling agent is a nonionic water-soluble polymer selected from the group consisting of hydroxypropyl cellulose and hydrophobically-modified hydroxypropyl methyl cellulose

Methodology Applied
Scientific EffectHydrogen bonding:

Implementation Method 2

hydrophobically-modified hydroxypropyl methyl cellulose

Methodology Applied
Scientific EffectHydrophobic interaction:

Implementation Method 3

a surfactant having an HLB of 14 or more

Methodology Applied
Scientific EffectSurface tension reduction: Surfactant

Implementation Method 4

an antioxidant

Methodology Applied
Scientific EffectOxidation prevention: Oxidation

Data Source

PatentEP3760198B1Diclofenac-containing emulsified gel composition
Publication Date: 2023.09.06 HISAMITSU PHARM CO INC
  • EP3760198B1 patent drawingFigure 1

AI summary

The present invention provides an emulsified gel composition comprising diclofenac sodium, water, a gelling agent, an antioxidant, and a surfactant having an HLB of 14 or more, in which the gelling agent is a nonionic water-soluble polymer.