Transdermal Patch Conversion Layer for Drug Permeation

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Solution Overview

Problem

Transdermal drug delivery faces limitations in the amount of drug that can be transported across the skin, with drug molecules in free base form being unstable and chemical enhancers often causing skin irritation.

Innovation Solution

The development of transdermal compositions with a multi-layer structure, including an active agent layer and a conversion layer containing a weak base and optionally a carboxylated component, which facilitates the conversion of drug salts to free base form upon skin contact, enhancing skin permeation while minimizing burst delivery and maintaining stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If drug molecules in free base form are used to increase skin permeation, then the amount of drug transported across skin is improved, but the stability of the drug is worsened

Engineering Contradiction:

Improveamount of drug transported across skinVSAvoidstability of drug

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The transdermal composition is divided into multiple layers: a drug-containing layer with drug in salt form (stable) and a conversion layer containing weak base (separate functional zones). This segmentation allows the drug to maintain stability in salt form while enabling conversion to free base form at the skin interface for permeation.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A conversion layer containing weak base acts as an intermediary between the stable drug salt and the skin. This intermediary converts the drug from salt form to free base form at the skin interface, enabling permeation without requiring the bulk drug to be in unstable free base form.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If chemical enhancers are used to increase skin permeation, then the delivery through skin is improved, but skin irritation is worsened

Engineering Contradiction:

Improvedelivery through skinVSAvoidskin irritation

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The invention changes the pH parameter locally at the skin interface by introducing a weak base in the conversion layer. This pH modification enables drug conversion and enhanced permeation without using harsh chemical enhancers that cause skin irritation.

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If drug is delivered in salt form to maintain stability, then the stability of the formulation is improved, but the skin permeation is worsened

Engineering Contradiction:

Improvestability of formulationVSAvoidskin permeation

Core Design Contradiction:

Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The composition segments the drug (in stable salt form) from the conversion function (weak base in separate layer). This allows the drug to remain in stable salt form in the formulation while the conversion layer provides the necessary conditions for free base formation and permeation at the skin interface.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The conversion layer is pre-positioned between the drug layer and the skin. Upon application, it preliminarily converts the drug to free base form right at the interface where permeation is needed, eliminating the need for the entire formulation to use unstable free base drug.

Inventive Principle:

Principle #10Preliminary action

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 transdermal compositions provide a substantially constant and prolonged delivery of active agents, such as propynylaminoindans, with reduced skin irritation and improved stability, achieving a therapeutically effective dosage over extended periods without significant degradation.

Implementation Method 1

a conversion layer, wherein the conversion layer includes a weak base... which facilitates the conversion of drug salts to free base form upon skin contact

Methodology Applied

Scientific EffectChemical reaction (salt to free base conversion): Chemical Bonding

Implementation Method 2

Transdermal patches deliver the active agent by percutaneous absorption, which is the absorption of substances through unbroken skin

Methodology Applied

Scientific EffectPercutaneous absorption: Absorption (physical)

Implementation Method 3

the active agent contained in the patch passes through, or permeates the skin and can reach its site of action through a systemic blood flow

Methodology Applied

Scientific EffectDiffusion: Diffusion

Data Source

PatentUS9119799B2Transdermal compositions comprising an active agent layer and an active agent conversion layer

Publication Date: 2015.09.01 TEIKOKU SEIYAKU CO LTD

AI summary

Transdermal compositions are provided. Aspects of the transdermal compositions include: an active agent layer and a conversion layer, where the conversion layer includes a weak base and, optionally, a carboxylated component. Also provided are methods of using the transdermal compositions and kits containing the transdermal compositions.