Retinoid O/W Emulsion Stability and Release Kinetics

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current topical pharmaceutical compositions face challenges in achieving physical and chemical stability, controlled release of active ingredients, and ease of application, particularly in penetrating the skin effectively and consistently, especially for retinoids which are prone to degradation and poor solubility in traditional solvents.

Innovation Solution

A stable oil-in-water emulsion composition is developed, using sucrose ester surfactants and specific solvents to solubilize retinoids, ensuring zero-order penetration kinetics and maintaining stability over time, with a formulation that includes a fatty phase, surfactants, polyols, and an aqueous phase to create a micro or submicron emulsion.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional solvents are used for retinoids, then retinoids can be solubilized, but the composition suffers from poor physical and chemical stability and retinoid degradation

Engineering Contradiction:
Improveretinoid solubilityVSAvoidphysical and chemical stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the physical-chemical parameters of the solvent system by replacing traditional organic solvents with a specific oil phase composition (caprylic/capric triglycerides, isopropyl myristate, mineral oil) and adjusting the surfactant system (sucrose esters, polyols) to achieve both retinoid solubility and enhanced stability, preventing degradation while maintaining dissolution

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite emulsion system combining multiple components: oil phase (caprylic/capric triglycerides, isopropyl myristate, mineral oil), surfactants (sucrose esters, polyols), and active retinoid compounds. This composite formulation provides synergistic effects where the combination stabilizes the retinoid better than any single component alone, achieving both solubility and stability

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If conventional cream or ointment formulations are used, then retinoids can be delivered to skin, but the release kinetics are uncontrolled and release occurs rapidly then plateaus

Engineering Contradiction:
Improveretinoid deliveryVSAvoidrelease kinetics control
Core Design Contradiction:
Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The patent incorporates retinoids into the oil phase and surfactant system during the formulation preparation stage, pre-establishing a stable dissolved state before application. This preliminary incorporation ensures controlled release kinetics from the start, preventing the rapid initial release followed by plateau that characterizes conventional formulations

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The surfactant system (sucrose esters and polyols) acts as an intermediary between the oil phase containing retinoids and the aqueous environment of the skin. This intermediary system controls the release kinetics by modulating the interface properties, enabling sustained controlled release rather than rapid release followed by plateau

Inventive Principle:
Principle #24Intermediary (Mediator)

3Duration of action of moving object

If transdermal patches are used for controlled release, then zero-order kinetics can be achieved, but the application area is limited by patch size and implementation is complex

Engineering Contradiction:
Improvecontrolled release kineticsVSAvoidformulation complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent extracts the controlled release function from the complex transdermal patch device and incorporates it directly into a simple cream/ointment formulation. By using a stabilized emulsion system with specific oil phases and surfactants, the formulation itself provides zero-order release kinetics without requiring external controlling devices, thereby simplifying the overall system while maintaining controlled release performance

Inventive Principle:
Principle #2Taking out (Extraction)

4Quantity of substance

If supersaturated solutions are used for increased concentration, then more active ingredient can be delivered, but physical stability is compromised and crystallization occurs

Engineering Contradiction:
Improveactive ingredient concentrationVSAvoidphysical stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the solubility parameters by using a specific oil phase composition (caprylic/capric triglycerides, isopropyl myristate, mineral oil) combined with surfactants (sucrose esters, polyols) that increase the solubility capacity for retinoids. This parameter change allows achieving high active ingredient concentrations in a stable supersaturated state without crystallization, as the modified solvent system maintains molecular dissolution at elevated concentrations

Inventive Principle:
Principle #35Parameter changes

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 achieves long-term, controlled release of retinoids with enhanced stability and skin penetration, maintaining at least 95% of the initial active ingredient content over six months, suitable for treating acne, ichthyoses, and psoriasis without greasiness.

Implementation Method 1

A stable oil-in-water emulsion composition is developed, using sucrose ester surfactants and specific solvents to solubilize retinoids

Methodology Applied
Scientific EffectSurfactant: Surfactant

Implementation Method 2

using sucrose ester surfactants and specific solvents to solubilize retinoids, ensuring zero-order penetration kinetics and maintaining stability over time

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 3

The composition achieves long-term, controlled release of retinoids with enhanced stability and skin penetration, maintaining at least 95% of the initial active ingredient content over six months

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2874619B1O/w-emulsion-type topical pharmaceutical compositions containing a retinoid
Publication Date: 2023.01.04 GALDERMA RESEARCH & DEVELOPMENT SNC
  • EP2874619B1 patent drawingFigure 1~2
  • EP2874619B1 patent drawingFigure 3
  • EP2874619B1 patent drawing

AI summary

The invention relates to o/w-emulsion-type topical pharmaceutical compositions containing a retinoid. The invention relates to a topical pharmaceutical composition comprising, by way of an active pharmaceutical ingredient, a retinoid in a physiologically acceptable composition. The invention also relates to the preparation method thereof and to the use of same in dermatology.