Crisaborole Topical Formulation Stability

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Solution Overview

Problem

Current topical pharmaceutical formulations for inflammatory skin conditions like atopic dermatitis and psoriasis face challenges with chemical and physical stability, necessitating a reformulation that improves efficacy and stability.

Innovation Solution

A topical pharmaceutical formulation comprising 5-(4-cyanophenoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, propylene glycol, butylated hydroxytoluene, edetate calcium disodium, mono- and di-glycerides, paraffin wax, and white petrolatum, which addresses stability issues and enhances treatment effectiveness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a partial suspension formulation of Crisaborole is used, then the formulation can be prepared, but chemical and physical stability issues occur

Engineering Contradiction:
Improveformulation preparationVSAvoidchemical and physical stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the physical state parameter of Crisaborole from partial suspension to complete dissolution by adjusting solvent composition (using propylene glycol as the primary solvent), thereby eliminating stability issues associated with suspensions while maintaining ease of manufacture

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite ointment formulation combining Crisaborole with multiple excipients (propylene glycol, petrolatum, mineral oil, cetyl alcohol, stearyl alcohol) to achieve both manufacturability and long-term chemical-physical stability

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If an ointment formulation is used, then beneficial emollient properties are achieved, but formulation stability challenges arise

Engineering Contradiction:
Improveemollient propertiesVSAvoidformulation stability
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent modifies the formulation composition parameters by using propylene glycol as the primary solvent to dissolve Crisaborole completely, and by incorporating specific stabilizers (edetate calcium disodium, butylated hydroxytoluene) to prevent oxidation and degradation, thereby achieving both emollient benefits and composition stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces propylene glycol as an intermediary substance that facilitates complete dissolution of Crisaborole and works synergistically with petrolatum and mineral oil to provide emollient properties while maintaining formulation stability through its solvating and stabilizing capabilities

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3383363B1Topical pharmaceutical formulations for treating inflammatory-related conditions
Publication Date: 2021.01.06 ANACOR PHARMACEUTICALS LLC
  • EP3383363B1 patent drawingFigure 1
  • EP3383363B1 patent drawingFigure 2
  • EP3383363B1 patent drawingFigure 3

AI summary

Topical pharmaceutical formulations, and methods of treating inflammatory conditions with these formulations, are disclosed.