Efinaconazole Composition Color Stability via BHT and EDTA
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Triazole antifungal compounds like efinaconazole exhibit instability during storage, leading to discoloration in pharmaceutical formulations, which can discourage patient use due to unsightly color changes.
Innovation Solution
A composition containing 0.5% to 15% efinaconazole, butylated hydroxytoluene (BHT), and a salt of ethylenediaminetetraacetic acid (EDTA) is formulated to maintain color stability, remaining colorless or pale yellow after storage for extended periods at high temperatures, using UV-vis absorbance values as a measure of stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If triazole antifungal compounds are formulated for topical delivery, then antifungal activity is achieved, but discoloration occurs during storage
Solution Approach 1:
The patent applies preliminary action by incorporating stabilizers (BHT and EDTA) into the formulation before storage. These stabilizers are added in advance to prevent discoloration from occurring during storage, rather than attempting to reverse discoloration after it happens. The stabilizers are pre-positioned in the composition to counteract oxidation and color changes that would otherwise occur during the storage period.
Solution Approach 2:
The patent converts the harmful effect of oxidation (which causes discoloration) into a beneficial outcome by using antioxidants. The oxidation process that would normally degrade the triazole compound and cause color changes is harnessed through controlled stabilization, where BHT and EDTA manage the oxidation process to prevent harmful discoloration while maintaining antifungal efficacy. The stabilizers transform the potentially harmful oxidative environment into a controlled condition that preserves both color and activity.
2Stability of the object's composition
If stabilizers are added to prevent discoloration, then color stability is improved, but formulation complexity increases
Solution Approach 1:
The patent applies parameter changes by optimizing the concentrations of stabilizers (BHT at 0.01-2% and EDTA at 0.0001-1.5%) to achieve effective color stabilization without excessive formulation complexity. By carefully controlling these parameter ranges, the formulation achieves stability while maintaining simplicity. The specific concentration parameters are tuned to provide sufficient stabilization with minimal additive amounts.
Solution Approach 2:
The patent uses composite materials by combining multiple stabilizers (BHT as an antioxidant and EDTA as a chelating agent) to achieve synergistic stabilization效果. This composite approach to stabilization allows each component to address different aspects of color degradation, providing comprehensive protection while keeping individual component concentrations relatively low, thus balancing effectiveness with formulation simplicity.
3Stability of the object's composition
If high concentrations of stabilizers are used, then color stability is enhanced, but cost and formulation complexity increase
Solution Approach 1:
The patent applies partial action by using stabilizer concentrations that are sufficient to achieve color stability without being excessive. The BHT concentration range of 0.01-2% and EDTA range of 0.0001-1.5% represent optimized partial amounts that provide adequate stabilization. This avoids the need for high concentrations of stabilizers, thereby controlling cost and formulation complexity while still achieving the desired color stability outcome.
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 effectively maintains color stability for at least three weeks at 40°C and one month at 65°C, ensuring the formulation remains effective and aesthetically acceptable for patient use, thereby enhancing treatment adherence.
Implementation Method 1
Certain formulations containing triazole active ingredients exhibit varying degrees of instability during storage. Certain formulations are known to discolor within storage periods as short as one or two days
Implementation Method 2
a salt of ethylenediaminetetraacetic acid (EDTA)
Implementation Method 3
UV-vis absorbance values as a measure of stability
Data Source
AI summary
The present invention provides compositions containing efinaconazole, butylated hydroxytoluene, a salt of ethylenediaminetetraacetic acid, and optional citric acid. The compositions exhibit stable color profiles and are useful in the treatment of fungal infections.