Amorphous Propranolol Ionic Liquid Transdermal Delivery

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Solution Overview

Problem

Current transdermal formulations of propranolol for treating infantile hemangioma face challenges such as skin irritation, limited drug size, and systemic side effects due to first-pass metabolism, necessitating the development of formulations that reduce skin irritation and enhance transdermal transport efficiency.

Innovation Solution

The formulation of amorphous melts or ionic liquids of propranolol with low viscosity, allowing direct application to the skin without organic solvents, which reduces skin irritation and maintains delivery efficiency comparable to crystalline propranolol free base, while providing higher flux due to improved solubility limitations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional transdermal formulations of propranolol are used, then therapeutic delivery can be achieved, but skin irritation occurs due to chemical stimulus from drugs and excipients

Engineering Contradiction:

Improvetherapeutic deliveryVSAvoidskin irritation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical state of propranolol from crystalline to amorphous, and formulates it as ionic liquids or eutectic mixtures. This parameter change in molecular arrangement and phase state reduces skin irritation while maintaining transdermal delivery effectiveness, directly resolving the contradiction between therapeutic delivery and skin irritation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite formulations by combining propranolol with specific ionic liquids or eutectic mixtures. These composite materials exhibit reduced skin irritation compared to pure propranolol, while maintaining or enhancing transdermal delivery, thus resolving the contradiction between therapeutic delivery and skin irritation.

Inventive Principle:

Principle #40Composite materials

2Reliability

If oral propranolol is administered, then systemic treatment is achieved, but first-pass metabolism reduces drug availability and causes systemic side effects

Engineering Contradiction:

Improvesystemic treatmentVSAvoiddrug availability

Core Design Contradiction:

ReliabilityVSLoss of substance

Solution Approach 1:

The patent extracts propranolol from the oral administration pathway and delivers it directly to the target site through transdermal application. This bypasses the first-pass metabolism in the liver, preventing drug degradation and systemic side effects while maintaining therapeutic effectiveness, thereby resolving the contradiction between systemic treatment and drug availability.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If transdermal delivery is used, then targeted delivery to skin lesions is achieved, but formulation complexity increases due to solubility and permeation requirements

Engineering Contradiction:

Improvetargeted deliveryVSAvoidformulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes propranolol to its amorphous state and formulates it as ionic liquids or eutectic mixtures, which inherently possess improved solubility and permeation properties. This parameter change simplifies the formulation requirements for transdermal delivery while maintaining targeted delivery to skin lesions, resolving the contradiction between targeted delivery and formulation complexity.

Inventive Principle:

Principle #35Parameter changes

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 amorphous melts or ionic liquids of propranolol demonstrate reduced skin irritation and enhanced transdermal transport, achieving therapeutic doses with lower irritation potential compared to traditional solutions, thus addressing the limitations of existing transdermal formulations.

Implementation Method 1

Amorphous melts or ionic liquids of propranolol with low viscosity, allowing direct application to the skin

Methodology Applied

Scientific EffectViscosity reduction:

Implementation Method 2

enhanced transdermal transport, achieving therapeutic doses with lower irritation potential

Methodology Applied

Scientific EffectTransdermal transport: Permeation

Implementation Method 3

providing higher flux due to improved solubility limitations

Methodology Applied

Scientific EffectSolubility improvement: Solvation

Data Source

PatentUS10828265B2Formulations of propranolol and analogs as an amorphous melt or ionic liquid for transdermal drug delivery

Publication Date: 2020.11.10 RGT UNIV OF CALIFORNIA

AI summary

Melts or ionic liquids containing amorphous propranolol, topical formulations and patches for transdermal drug delivery, and methods of making and using thereof are described herein. The melts or ionic liquids may be in a topical drug delivery formulation or patch to be applied to the skin. The drug delivery formulation or patch contains a sufficient amount of the amorphous propranolol to deliver a therapeutically effective amount of the amorphous propranolol to the patient in need of treatment, such as for the treatment or amelioration of infantile hemangioma. The formulations have a low viscosity and reduced skin irritation compared to the crystalline propranolol free base (PFB). The melts or ionic liquids can be formed by a salt metathesis reaction.