Transdermal Composition Stabilizing Fatty Acids via Buffer

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Solution Overview

Problem

Transdermal or transmucous pharmaceutical compositions containing fatty acids as percutaneous absorption promoters face stability issues due to esterification reactions in aqueous-alcoholic solutions, leading to variability in bioavailability and efficacy over time, which is a concern for patient safety and product consistency.

Innovation Solution

Incorporating a buffer and/or a fatty acid ester as a stabilizer in the pharmaceutical composition to maintain chemical stability, with specific pH and concentration ranges, and using an alcoholic vehicle like ethanol to enhance skin penetration while preventing esterification of fatty acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If fatty acids are used as percutaneous absorption promoters in aqueous-alcoholic compositions, then skin penetration of active substances is improved, but chemical stability deteriorates due to esterification reactions

Engineering Contradiction:

Improveskin penetration efficiencyVSAvoidchemical stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent introduces an intermediary substance (buffer or ester) that mediates between the fatty acid and alcohol components. The buffer (e.g., carbonate/bicarbonate) or ester (e.g., ethyl oleate) acts as a mediator to prevent direct esterification reaction between fatty acid and alcohol, while still allowing the formulation to maintain its percutaneous absorption promoting function.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the formulation by adjusting pH (using buffers to maintain pH 4-10) and by introducing ester compounds. These parameter changes modify the chemical environment to prevent esterification while preserving the absorption-promoting activity of the fatty acid.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If fatty acids are used to promote percutaneous absorption, then bioavailability of active substance is improved, but reliability deteriorates due to composition variability over time

Engineering Contradiction:

ImprovebioavailabilityVSAvoidcomposition consistency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-stabilizing the fatty acid through buffer addition or ester formation during formulation preparation. This preliminary stabilization prevents future composition changes, ensuring that the bioavailability and efficacy remain consistent throughout the product's shelf life.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent incorporates feedback mechanisms through the use of buffers that maintain pH within a specific range (4-10), and esters that provide feedback stability. These components continuously monitor and adjust the chemical environment to prevent degradation, ensuring consistent composition and efficacy over time.

Inventive Principle:

Principle #23Feedback

3Ease of operation

If aqueous-alcoholic vehicle is used for transdermal administration, then ease of application is improved, but stability worsens due to esterification of fatty acids

Engineering Contradiction:

Improveease of applicationVSAvoidchemical stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The buffer or ester acts as an intermediary that allows the aqueous-alcoholic vehicle to maintain its ease of application properties while preventing the harmful esterification reaction. The intermediary substance decouples the beneficial solubility properties of the alcoholic vehicle from the instability caused by fatty acid-reactive conditions.

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 remains chemically and physically stable for extended periods, ensuring consistent bioavailability and efficacy of the active substance, thereby ensuring patient safety and product integrity.

Implementation Method 1

fatty acid as percutaneous absorption promoter

Methodology Applied

Scientific EffectPercutaneous absorption: Absorption (physical)

Implementation Method 2

promotes the reversible diffusion of an active principle through the skin

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 3

adding a buffer... capable of stabilizing the fatty acid in the pharmaceutical composition

Methodology Applied

Scientific EffectBuffering:

Implementation Method 4

the fatty acid undergoes an esterification reaction... oleic acid is converted into ethyl oleate

Methodology Applied

Scientific EffectEsterification reaction: Chemical Bonding

Implementation Method 5

adding small amounts of an ester of the corresponding acid... capable of stabilizing the fatty acid

Methodology Applied

Scientific EffectStabilization:

Data Source

PatentUS7611727B2Pharmaceutical composition for transdermal or transmucous administration

Publication Date: 2009.11.03 BESINS HEALTHCARE LUXEMBOURG SARL(LU)

AI summary

The present invention relates to a novel pharmaceutical composition for transdermal or transmucous administration of at least one active substance, and comprising especially a fatty acid as a percutaneous absorption promoter, at least one alcoholic vehicle and also a stabilizer capable of stabilizing the fatty acid in the said pharmaceutical composition.