Tolterodine Patch Stability via Tartrate Salt Formulation
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Solution Overview
Problem
Current tolterodine-containing patches using a free base face issues with stability during storage due to reaction with base ingredients and cause skin irritation, leading to decreased active ingredient content and adverse effects.
Innovation Solution
A tolterodine-containing patch with an adhesive layer comprising a styrene-isoprene-styrene block copolymer, a tackifier resin, and a softener, where tolterodine is present as a free base, optimizing the transdermal permeation rate and stability, and reducing skin irritation by adjusting the composition and adding a multivalent metal salt.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a tolterodine free base is used to increase transdermal absorbability, then transdermal absorbability is improved, but formulation stability deteriorates due to reaction with base ingredients and decomposition
Solution Approach 1:
The patent changes the chemical form of tolterodine from free base to acid addition salt (specifically tolterodine tartrate) to alter its stability characteristics while maintaining transdermal absorbability. This parameter change resolves the contradiction by selecting a different chemical state that balances both absorption and stability requirements.
Solution Approach 2:
The patent introduces an acid addition salt (tartrate) as an intermediary compound between tolterodine and the base ingredient. This intermediary form prevents direct reaction between tolterodine and basic components in the adhesive formulation, thereby maintaining formulation stability while preserving the ability to achieve transdermal absorption.
2Productivity
If a tolterodine free base is used to enhance transdermal permeation, then transdermal permeation is improved, but skin irritation increases
Solution Approach 1:
The patent changes the chemical form of tolterodine from free base to acid addition salt, which modifies the pharmacological and dermatological properties. This parameter change reduces skin irritation while maintaining transdermal permeation effectiveness, as the salt form has different interaction characteristics with skin proteins and enzymes compared to the free base.
3Ease of manufacture
If an acrylic adhesive is used as base ingredient, then ease of manufacture is improved, but formulation stability deteriorates due to decomposition of active ingredient
Solution Approach 1:
The patent uses tolterodine tartrate as an intermediary form that acts as a buffer between the active ingredient and the acrylic adhesive matrix. This intermediary salt form prevents direct chemical interaction between tolterodine and the acrylic adhesive components, thereby maintaining active ingredient stability while preserving ease of manufacture.
Solution Approach 2:
The patent changes the formulation approach by using an acid addition salt instead of free base with acrylic adhesive. This parameter change in the drug form allows compatibility with acrylic adhesive while maintaining stability, resolving the contradiction between ease of manufacture and formulation stability.
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 patch achieves excellent transdermal absorbability and stability while minimizing skin irritation, maintaining effective drug efficacy and physical properties.
Implementation Method 1
a constant blood drug concentration can be maintained and the administration can easily be discontinued by peeling off the patch when a side effect occurs
Data Source
AI summary
The present invention provides a tolterodine-containing patch in which an adhesive layer is laminated on a backing, characterized in that the adhesive layer is obtainable by adding tolterodine to an adhesive base comprising a rubber adhesive, a tackifier resin, and a softener, wherein the tolterodine is present in the form of a free base in the adhesive base.