Topical Formulation Using Multiplexed Penetration Enhancers
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Solution Overview
Problem
Current topical formulations for transdermal drug administration face limitations due to the skin's impermeable nature, particularly the stratum corneum, which hinders the effective delivery of active agents, and many molecular penetration enhancers are either ineffective or cause skin irritation, restricting the range of drugs suitable for transdermal use.
Innovation Solution
A topical formulation combining specific multiplexed molecular penetration enhancers such as N-lauroyl sarcosine, sodium octyl sulfate, methyl laurate, isopropyl myristate, oleic acid, glyceryl oleate, and sodium lauryl sulfoacetate to enhance skin permeability, allowing for improved delivery of active agents through the skin with reduced irritation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If molecular penetration enhancers are used to increase skin permeability, then the flux of active agents through the skin is improved, but skin irritation occurs
Solution Approach 1:
The patent combines multiple penetration enhancers (isopropyl myristate, oleic acid, and other esters) into a composite formulation that achieves enhanced skin permeability while reducing individual component irritation. This composite approach allows synergistic effects where the combination provides better flux than individual components alone while minimizing harmful side effects.
Solution Approach 2:
The patent optimizes the concentration ratios and molecular weight parameters of different penetration enhancers in the formulation. By adjusting these parameters, the formulation achieves effective skin permeability enhancement while maintaining irritation levels within acceptable ranges. Specific concentration ranges are identified to balance flux improvement with skin tolerance.
2Productivity
If the stratum corneum barrier is reduced to allow drug penetration, then transdermal delivery is improved, but skin protection function is compromised
Solution Approach 1:
The penetration enhancers are applied in controlled amounts and contact times to temporarily modify stratum corneum permeability only during the treatment period. The formulation is designed to revert to normal barrier function after application is removed, thus achieving transdermal delivery without permanent compromise of skin protection.
Solution Approach 2:
The formulation applies partial penetration enhancement - enough to achieve therapeutic drug levels in the skin or systemic circulation, but not so much as to cause excessive barrier disruption. The concentration and contact time are optimized to achieve the minimum necessary enhancement for effective drug delivery while preserving skin integrity.
3Productivity
If high concentrations of penetration enhancers are used to overcome skin impermeability, then drug flux is increased, but formulation complexity and cost increase
Solution Approach 1:
The patent combines multiple penetration enhancers with complementary mechanisms of action into a single formulation. This merging allows lower concentrations of each individual component to achieve the same or better flux than high concentrations of a single enhancer, thereby reducing formulation complexity and manufacturing costs while maintaining effective drug delivery.
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 formulation significantly increases the flux of active agents through the skin, expanding the range of drugs suitable for transdermal administration while minimizing skin irritation, thus overcoming the limitations of existing penetration enhancers.
Implementation Method 1
Molecular penetration enhancers or 'MPETM's' can enhance the diffusion of molecules across the skin by, for example, disrupting the lipid bilayers of the stratum corneum.
Implementation Method 2
Molecular penetration enhancers or 'MPETM's' can enhance the diffusion of molecules across the skin by, for example, disrupting the lipid bilayers of the stratum corneum.
Data Source
AI summary
It has been discovered that certain combinations compounds are excellent penetration enhancers and, as such, can be incorporated in a topical formulation to facilitate administration of active agents. The increased penetration enhancement can also lead to a reduction in the total concentration of skin irritants in the formulation. There is described herein a topical formulation comprising (i) at least one active agent; (ii) a first compound, and (iii) a second compound, wherein the first compound and second compound are different, and each is selected from the group consisting of N-lauroyl sarcosine, sodium octyl sulfate, methyl laurate, isopropyl myristate, oleic acid, glyceryl oleate and sodium lauryl sulfoacetate.