Topical Composition with Liquid Oil Phase for Crisaborole Solvation

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Solution Overview

Problem

Existing crisaborole formulations, such as ointments and creams, suffer from poor aesthetics, limited patient compliance, and inadequate skin permeation, stability, and solvation, particularly at high concentrations, due to the use of solidified oil phases that hinder diffusion.

Innovation Solution

A topical composition with a discontinuous liquid oil phase in a continuous aqueous phase, incorporating specific oils and surfactants to ensure crisaborole remains fully solvated and enhances skin penetration, while avoiding solidifying agents, resulting in improved stability and aesthetics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a solidified oil phase is used in crisaborole formulations, then the formulation has better aesthetic profile and improved patient compliance, but the crisaborole crystallises out and skin permeation is hindered

Engineering Contradiction:
Improvepatient complianceVSAvoidskin permeation
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent changes the physical state of the oil phase from solid to liquid by selecting specific liquid oils (isopropyl myristate, isopropyl isostearate, isopropyl palmitate) instead of solidified oils. This parameter change prevents crisaborole crystallization while maintaining formulation stability and improving skin permeation, as the liquid oil phase keeps the active ingredient fully solvated.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent avoids phase transitions that would cause crisaborole to crystallize. By maintaining the oil phase in a liquid state at application temperature and avoiding solidifying agents, the formulation prevents the phase transition that leads to drug precipitation, ensuring consistent drug delivery and skin permeation.

Inventive Principle:
Principle #36Phase transitions

2Stability of the object's composition

If a solid emulsifying and structuring agent is used to solidify the oil phase, then the formulation achieves physical stability, but the crisaborole diffusion into skin is restricted

Engineering Contradiction:
Improvephysical stabilityVSAvoiddrug diffusion
Core Design Contradiction:
Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The patent extracts and removes solid emulsifying and structuring agents from the formulation. By eliminating these solidifying components, the oil phase remains liquid, allowing crisaborole to diffuse freely into the skin while the formulation maintains stability through the selection of appropriate liquid oils and emulsifiers.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the formulation parameters by excluding solid emulsifying and structuring agents. This parameter change maintains physical stability through alternative means (liquid oil selection, emulsifier composition) while preserving drug diffusion capability by keeping the oil phase liquid.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If crisaborole is present at high concentration in cream formulations, then the therapeutic effect is enhanced, but the drug tends to crystallise out giving rise to physical instability

Engineering Contradiction:
Improvecrisaborole concentrationVSAvoidphysical instability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the solvent parameters by using specific liquid oils (isopropyl myristate, isopropyl isostearate, isopropyl palmitate) with high crisaborole solubility. This parameter change allows high drug concentration (2% or higher) to be maintained in solution without crystallization, preventing physical instability while preserving therapeutic efficacy.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite oil phase system combining multiple liquid oils with complementary properties. This composite approach enhances overall crisaborole solubility and formulation stability at high concentrations, preventing crystallization through synergistic interactions between the different oil components.

Inventive Principle:
Principle #40Composite materials

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 enhanced skin permeation, stability, and patient compliance by maintaining crisaborole solvation, reducing skin irritation, and providing a more appealing application experience.

Implementation Method 1

the discontinuous liquid oil phase serves to solvate the crisaborole

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

achieves improved skin penetration compared with the formulations containing a solidified oil phase

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP3829538B1Topical composition
Publication Date: 2025.07.02 MC2 THERAPEUTICS LTD
  • EP3829538B1 patent drawingFigure 1
  • EP3829538B1 patent drawingFigure 2

AI summary

The present invention relates to a composition for topical application comprising a continuous aqueous phase, a discontinuous liquid oil phase and crisaborole.