Non-aqueous Diclofenac Solution for Transdermal Delivery

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Solution Overview

Problem

Existing topical diclofenac formulations often result in excessive drug concentration in blood plasma due to non-optimized delivery systems, leading to side effects, and most formulations rely on water as a key component for penetration enhancement, which may not be ideal for all skin types and conditions.

Innovation Solution

A non-aqueous topical solution composition of diclofenac with diethylamine salt, utilizing lower chain alcohols like ethanol as penetration enhancers and solubilizers, along with solvents such as propylene glycol, and optional counter-irritants and humectants, to enhance transdermal penetration without dehydration or greasiness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aqueous formulations are used to enhance transdermal penetration through hydration of skin and solvation of intercellular lipids, then permeability of the active ingredient is increased, but excessive drug concentration in blood plasma is delivered leading to side effects

Engineering Contradiction:

Improvepermeability of active ingredientVSAvoidexcessive drug concentration in blood plasma

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the fundamental parameter of the formulation base from aqueous to non-aqueous (using propylene glycol as the primary vehicle). This parameter change fundamentally alters the delivery mechanism, allowing for enhanced transdermal penetration through solvation of intercellular lipids without the excessive plasma concentration issues associated with aqueous formulations. The non-aqueous base provides controlled release and improved safety profile.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The formulation employs a composite approach by combining diclofenac diethylamine salt with propylene glycol as the primary vehicle and ethanol as a co-solvent/penetration enhancer. This composite formulation leverages the synergistic effects of different components: propylene glycol provides the non-aqueous base for lipid solvation, while ethanol enhances penetration through additional lipid disruption and solubility improvement, achieving reliable delivery without excessive plasma concentration.

Inventive Principle:

Principle #40Composite materials

2Reliability

If water is used as an essential component in topical preparations to aid permeation of the active drug, then transdermal absorption is enhanced, but dehydration of skin occurs and greasiness is produced

Engineering Contradiction:

Improvetransdermal absorptionVSAvoiddehydration of skin

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Instead of using water (aqueous base) to enhance penetration, the patent inverts the approach by using a non-aqueous base (propylene glycol). This inversion achieves the penetration enhancement goal through a different mechanism - solvation of intercellular lipids rather than hydration of the stratum corneum - thereby avoiding the harmful side effect of skin dehydration while maintaining reliable transdermal absorption.

Inventive Principle:

Principle #13The other way round (Inversion)

3Object-affected harmful factors

If non-aqueous solution is used to avoid dehydration and greasiness, then skin comfort is improved, but transdermal penetration may be reduced compared to aqueous formulations

Engineering Contradiction:

Improveskin dehydration and greasinessVSAvoidtransdermal penetration

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent introduces ethanol as an intermediary substance that bridges the gap between non-aqueous formulation and effective transdermal penetration. Ethanol acts as a penetration enhancer that disrupts intercellular lipids and increases skin permeability, allowing the non-aqueous propylene glycol base to effectively deliver diclofenac diethylamine salt through the skin while maintaining skin comfort without dehydration or greasiness.

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 non-aqueous solution achieves higher blood plasma levels of diclofenac with enhanced bioavailability and analgesic action, characterized by increased AUC and Cmax values, outperforming conventional aqueous formulations in bioequivalence studies.

Implementation Method 1

utilizing lower chain alcohols like ethanol as penetration enhancers and solubilizers

Methodology Applied

Scientific EffectSolubilization: Solvation

Implementation Method 2

utilizing lower chain alcohols like ethanol as penetration enhancers

Methodology Applied

Scientific EffectPermeation enhancement: Permeation

Implementation Method 3

along with solvents such as propylene glycol

Methodology Applied

Scientific EffectDissolution: Solvation

Data Source

PatentUS10702469B2Non-aqueous topical solution of diclofenac and process for preparing the same

Publication Date: 2020.07.07 TROIKAA PHARMACEUTICALS LTD

AI summary

A non-aqueous topical solution composition of pharmaceutically acceptable salt of diclofenac is disclosed. The non-aqueous topical solution composition comprises therapeutically effective amount of pharmaceutically acceptable salt of diclofenac, solublizer, penetration enhancer and solvent, and optionally a humectant, counter irritant, additional penetration enhancer and anti-oxidants and a process for preparing the same.