Transdermal Patch Microreservoirs for Ion Pair Delivery

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Solution Overview

Problem

Transdermal therapeutic systems face challenges in using ion pairs of active pharmaceutical ingredients and additives, as they reduce the cohesion of polymer matrices, impairing adhesiveness and limiting active ingredient flux due to solvents' low solubility and migration issues.

Innovation Solution

A transdermal therapeutic system with a polysiloxane polymer base containing microreservoirs where active ingredients are present as ion pairs with oppositely charged physiologically acceptable additives in equimolar quantities, without solvents, to enhance thermodynamic activity and minimize polymer structure influence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If ion pairs of active pharmaceutical ingredients and additives are used to enhance skin permeation, then active ingredient flux is improved, but polymer matrix cohesion is reduced and adhesiveness is impaired

Engineering Contradiction:
Improveactive ingredient fluxVSAvoidpolymer matrix cohesion
Core Design Contradiction:
ProductivityVSStrength

Solution Approach 1:

The patent divides the system into separate microreservoirs containing ion pairs, isolating the active ingredient and ion pair former from the bulk polymer matrix. This segmentation allows the ion pairs to enhance permeation without significantly compromising the overall matrix cohesion, as the ion pairs are confined to discrete reservoirs rather than being distributed throughout the entire polymer structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates local regions (microreservoirs) with different properties within the polymer matrix. These reservoirs contain the ion pairs and have specific solubility characteristics that enhance active ingredient delivery, while the surrounding polymer matrix maintains its structural integrity and adhesiveness. This local differentiation allows simultaneous optimization of permeation and matrix strength.

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If solvents are used to dissolve active ingredients in microreservoirs, then active ingredient saturation is improved, but solvent migration and low solubility issues occur

Engineering Contradiction:
Improveactive ingredient saturationVSAvoidsolvent migration stability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent extracts and eliminates solvents from the microreservoir system. Instead of using solvents to dissolve active ingredients, the invention employs a solvent-free approach where ion pairs directly facilitate active ingredient saturation and permeation. This removal of solvents eliminates migration issues and improves system reliability while maintaining active ingredient delivery effectiveness.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the fundamental parameter of the microreservoir composition from solvent-based to ion pair-based. By transitioning from a solvent dissolution mechanism to an ion pair formation mechanism, the system achieves active ingredient saturation without relying on solvents that would otherwise migrate or crystallize, thereby improving reliability.

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

This approach increases active ingredient saturation and permeation while maintaining matrix cohesion, achieving higher thermodynamic activity and skin delivery efficiency without solvent-related issues.

Implementation Method 1

Ion pairs are physicochemical molecular associations consisting of two charged molecules which form, through effective neutralization of the ionic conditions, an association which has an externally virtually neutral appearance and is thus more lipophilic. The active ingredient which is in each case part of this association is thus converted into a form which is more lipophilic, more diffusible and thus more suitable for skin permeation.

Methodology Applied
Scientific EffectIon pair formation:

Implementation Method 2

These ambiphilic solvents dissolve the active ingredient during storage in such a way that it does not crystallize, and, after the transdermal therapeutic system has been stuck on, they leave the matrix through migration into the skin and subsequently leave behind a supersaturation with consequently increased thermodynamic activity of the active ingredient.

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 3

these ambiphilic solvents dissolve the active ingredient during storage in such a way that it does not crystallize

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 4

after the transdermal therapeutic system has been stuck on, they leave the matrix through migration into the skin

Methodology Applied
Scientific EffectMigration:

Implementation Method 5

with the aid of the side directly facing the skin (adhesive layer), an at least temporarily adhesive connection to the skin

Methodology Applied
Scientific EffectAdhesion: Adhesive

Data Source

PatentUS9089527B2Transdermal therapeutic system comprising ion pair microreservoirs
Publication Date: 2015.07.28 LTS LOHMANN THERAPIE SYST AG

AI summary

The invention relates to a transdermal therapeutic system which comprises a back layer that is impermeable to the active substance, and a peelable protective layer that is impermeable to the active substance and at least one matrix layer consisting of polysiloxanes and/or polysiloxane derivatives and containing micro-reservoirs. Said micro-reservoirs contain at least one ion pair from a pharmacologically active substance and an additive and either the active substance is nucleophilic and the additive is electrophilic or the active substance is electrophilic and the additive is nucleophilic.