Transdermal Patch Organic Acid Diclofenac Solubility

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Solution Overview

Problem

Current treatments for osteoarthritis, such as transdermal diclofenac patches, face challenges in achieving effective and safe drug release and skin permeability, necessitating the development of a patch with improved formulations.

Innovation Solution

A patch comprising a backing layer and an adhesive layer with diclofenac sodium, dimethyl sulfoxide, and an organic acid, where the organic acid content is 6-8% of the adhesive layer's total mass, applied once daily to provide a dose of 70-150 mg diclofenac sodium, enhancing skin permeability and preventing crystal precipitation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a high concentration of diclofenac sodium is used in the adhesive layer, then the therapeutic effect is improved, but the risk of crystal precipitation and skin irritation increases

Engineering Contradiction:
Improvetherapeutic effectVSAvoidcrystal precipitation and skin irritation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Dimethyl sulfoxide (DMSO) is used as a penetration enhancer and solvent intermediary that facilitates the dissolution of diclofenac sodium and prevents crystal precipitation. The organic acid component acts as another intermediary that maintains drug solubility in the adhesive matrix, allowing high drug concentrations without precipitation or excessive irritation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent optimizes the concentration of organic acid to 6-8 mass% and DMSO to 5-10 mass% in the adhesive layer. These parameter changes create an optimal chemical environment that maintains diclofenac sodium solubility at high concentrations while controlling skin permeability to prevent irritation.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If the organic acid content is increased to improve skin permeability, then drug absorption is enhanced, but the risk of skin irritation increases

Engineering Contradiction:
Improveskin permeabilityVSAvoidskin irritation
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The organic acid content is precisely controlled within 6-8 mass% of the adhesive layer total mass. This optimized parameter range provides sufficient skin permeability enhancement while maintaining safety margins below irritation thresholds. The balanced formulation achieves effective drug delivery without excessive acidity that would cause irritation.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If the patch is applied frequently to maintain therapeutic levels, then efficacy is improved, but patient compliance and safety decrease due to cumulative exposure

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidcumulative exposure and safety
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patch is designed for once-daily application, creating a periodic dosing regimen that maintains therapeutic drug levels while allowing sufficient elimination time between doses. This periodic action pattern prevents cumulative toxicity while ensuring continuous therapeutic effect throughout the day.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The controlled-release adhesive matrix provides continuous drug delivery over 24 hours, ensuring uninterrupted therapeutic action at the application site. This continuous local action maintains effective concentrations without requiring frequent reapplication, thereby preventing cumulative systemic exposure.

Inventive Principle:
Principle #20Continuity of useful action

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 patch effectively alleviates osteoarthritis pain, particularly for knee osteoarthritis, with optimal pharmacokinetic parameters including maximum plasma concentration, half-life, and area under plasma concentration-time curve, ensuring safety and efficacy in treating osteoarthritis.

Implementation Method 1

dimethyl sulfoxide, wherein a content of the organic acid is 6 mass % to 8 mass % with respect to a total mass of the adhesive layer

Methodology Applied
Scientific EffectSkin permeability enhancement: Permeation

Implementation Method 2

an organic acid, wherein a content of the organic acid is 6 mass % to 8 mass % with respect to a total mass of the adhesive layer

Methodology Applied
Scientific EffectCrystal precipitation prevention: Solvation

Data Source

PatentUS20240122870A1Transdermal patch for treating osteoarthritis
Publication Date: 2024.04.18 HISAMITSU PHARM CO INC

AI summary

Disclosed is a transdermal patch for treating osteoarthritis. The transdermal patch comprises a support layer and an adhesive layer laminated on the support layer. The adhesive layer includes an adhesive base, diclofenac sodium, dimethyl sulfoxide, and an organic acid. The organic acid content is 6-8 mass % of the total mass of the adhesive layer. The transdermal patch is applied once daily to an affected part and the dosage of diclofenac sodium per application is 70-150 mg.