Fesoterodine Solid Dispersion Stabilization
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Solution Overview
Problem
Fesoterodine hydrogen fumarate is known for its instability, particularly requiring refrigeration for storage in pharmaceutical formulations, and existing formulations with xylitol-based stabilizers have limitations in stability and compatibility for certain applications.
Innovation Solution
A solid molecular dispersion comprising fesoterodine hydrogen fumarate in a weight ratio of 3:97 to 12:88 with alkyl hydroxyalkylcellulose ethers or hydroxyalkylcellulose ethers, which stabilizes the compound without crystalline or amorphous forms, providing improved chemical stability and allowing for modified-release formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fesoterodine hydrogen fumarate is stored in crystalline form, then it can be formulated for pharmaceutical use, but it requires refrigeration to maintain stability
Solution Approach 1:
The patent changes the physical state parameter of fesoterodine hydrogen fumarate from crystalline to amorphous within a solid dispersion matrix, which fundamentally alters its stability characteristics and eliminates the need for refrigeration while maintaining chemical stability
Solution Approach 2:
The patent creates a composite material system where fesoterodine hydrogen fumarate is dispersed within a matrix of alkyl hydroxyalkylcellulose ether or hydroxyalkylcellulose ether, forming a solid molecular dispersion that provides both stability and room-temperature storage capability
2Reliability
If xylitol-based stabilizers are used in tablet formulations, then chemical stability is achieved, but compatibility and adaptability for certain applications (particularly pediatric use) are limited
Solution Approach 1:
The patent changes the stabilizing mechanism from using xylitol-based compounds to using alkyl hydroxyalkylcellulose ether or hydroxyalkylcellulose ether as the matrix material, which fundamentally alters the formulation properties and enables better adaptability for pediatric and other specialized applications while maintaining stability
Solution Approach 2:
The patent uses alkyl hydroxyalkylcellulose ether or hydroxyalkylcellulose ether as an intermediary matrix material that facilitates the dispersion and stabilization of fesoterodine hydrogen fumarate, providing both stability and improved compatibility for various applications including pediatric use
3Ease of manufacture
If fesoterodine is prepared as an oil, then it can be obtained, but it presents difficulty for pharmaceutical formulation and processing
Solution Approach 1:
The patent utilizes phase transition by incorporating fesoterodine hydrogen fumarate into a solid dispersion matrix, transforming it from an unstable oil or crystalline form into a stable amorphous state within the polymer matrix, which provides both formulation ease and chemical stability
Solution Approach 2:
The patent creates a composite material system where fesoterodine hydrogen fumarate is dispersed within a matrix of alkyl hydroxyalkylcellulose ether or hydroxyalkylcellulose ether, forming a solid molecular dispersion that provides both formulation ease and chemical stability
Data Source
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AI summary
The present invention relates to solid molecular dispersion of fesoterodine hydrogen fumarate and a polymeric binder. The invention also relates to an inert core bead or particle which is coated with said solid molecular dispersion and to pharmaceutical formulations comprising such coated beads or particles.