Halobetasol Propionate Formulation with Multiplexed Penetration Enhancers

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Solution Overview

Problem

Formulating topical compositions for skin application is challenging due to the skin's barrier properties, particularly the stratum corneum, which limits the delivery of active agents, and existing excipients often cause irritation, stability issues, or compatibility problems.

Innovation Solution

A pharmaceutical composition including halobetasol propionate, ethoxylated castor oil, and multiplexed molecular penetration enhancers such as N-lauroyl sarcosine, sodium octyl sulfate, methyl laurate, isopropyl myristate, oleic acid, or sodium lauryl sulfoacetate, which improve skin penetration and stability without relying on high concentrations of ethoxylated castor oil.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If molecular penetration enhancers are used to disrupt lipid bilayers and improve active agent penetration, then skin penetration is improved, but excipient irritation and formulation stability deteriorate

Engineering Contradiction:

Improveskin penetrationVSAvoidexcipient irritation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of penetration enhancers by selecting compounds with specific molecular weights (200-500 Da), logP values (2-4), and hydrogen bond donor/acceptor counts that optimize skin penetration while minimizing irritation. This parameter optimization resolves the contradiction between effective penetration and reduced irritation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses composite formulations combining multiple penetration enhancers (e.g., oleic acid with ethoxylated castor oil, or sodium lauryl sulfoacetate with isopropyl myristate) in specific ratios. This composite approach synergistically improves penetration while the diverse composition reduces irritation compared to single enhancers.

Inventive Principle:

Principle #40Composite materials

2Reliability

If high concentrations of ethoxylated castor oil are used as penetration enhancer, then skin penetration is improved, but excipient irritation and formulation stability deteriorate

Engineering Contradiction:

Improveskin penetrationVSAvoidformulation stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration parameter of ethoxylated castor oil to specific ranges (0.1-5% w/w, preferably 0.5-2% w/w) rather than using high concentrations. This parameter control maintains penetration enhancement while preventing pH degradation and formulation instability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces alternative penetration enhancers as intermediary substances that can achieve similar penetration effects without the destabilizing properties of high concentrations of ethoxylated castor oil. These intermediaries (e.g., oleic acid, sodium lauryl sulfoacetate) provide penetration enhancement while maintaining formulation stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If existing excipients are used to enhance penetration, then active agent delivery is improved, but compatibility issues and shelf life deteriorate

Engineering Contradiction:

Improveactive agent deliveryVSAvoidshelf life

Core Design Contradiction:

ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent selects penetration enhancers with specific chemical parameters (molecular weight 200-500 Da, logP 2-4, specific hydrogen bonding capacity) that ensure both effective active agent delivery and long-term formulation stability. This parameter-based selection resolves the contradiction between delivery efficiency and shelf life.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs penetration enhancers that are effective at low concentrations (0.1-5% w/w), reducing their impact on formulation stability over time. The low usage levels of these enhancers minimize their potential to cause degradation, effectively treating them as temporary facilitators rather than long-term stabilizers.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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 penetration and stability of halobetasol propionate, with improved vasoconstriction assay scores and extended shelf life, reducing the need for potentially irritating excipients and maintaining potency over time.

Implementation Method 1

These enhancers can disrupt the lipid bilayers of the stratum corneum; thereby, allowing active agent(s) to penetrate or cross the lipid bilayers of the stratum corneum

Methodology Applied

Scientific EffectLipid bilayer disruption:

Implementation Method 2

The composition achieves enhanced skin penetration and stability of halobetasol propionate, with improved vasoconstriction assay scores

Methodology Applied

Scientific EffectVasoconstriction:

Data Source

PatentUS11642356B2Pharmaceutical compositions

Publication Date: 2023.05.09 CRESCITA THERAPEUTICS INC

AI summary

In one example presented herein, is a pharmaceutical composition. The pharmaceutical composition can include halobetasol propionate, from 0 wt % to 3 wt % ethoxylated castor oil, a first compound, and a second compound. The first compound and the second compound can be selected from; N-lauroyl sarcosine, sodium octyl sulfate, methyl laurate, isopropyl myristate, oleic acid, glyceryl oleate, and sodium lauryl sulfoacetate. The first compound and the second compound are not the same.