Linagliptin Amorphous Solid Dispersion Stability
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Solution Overview
Problem
Linagliptin exhibits polymorphic forms that are not reproducible or stable, affecting its pharmaceutical properties such as solubility and stability, which is crucial for its handling, shelf life, and commercial acceptance.
Innovation Solution
A novel amorphous solid dispersion of linagliptin is developed in combination with pharmaceutically acceptable carriers like copovidone, ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, or soluplus, prepared by dissolving the mixture in a solvent and removing it to create a stable form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crystalline polymorphic forms of linagliptin are used, then the drug can be handled and processed, but the forms are not stable and not reproducible, affecting shelf life and commercial acceptance
Solution Approach 1:
The patent transforms linagliptin from a crystalline polymorphic state to an amorphous solid dispersion state, fundamentally changing the physical state parameter. This amorphous form provides both stability and reproducibility, resolving the contradiction between reliability and compositional stability that plagued the crystalline polymorphic forms.
Solution Approach 2:
The patent creates a composite material system by dispersing linagliptin in pharmaceutically acceptable carriers (such as copovidone, hydroxypropyl methylcellulose, polyethylene glycol, or soluplus). This composite amorphous solid dispersion approach ensures both stability and reproducibility, overcoming the limitations of pure crystalline polymorphic forms.
2Reliability
If amorphous forms of linagliptin are used, then stability and reproducibility are improved, but amorphous forms are typically hygroscopic which affects handling properties
Solution Approach 1:
The patent introduces pharmaceutically acceptable carriers (copovidone, hydroxypropyl methylcellulose, polyethylene glycol, or soluplus) as intermediary substances. These carriers embed the amorphous linagliptin molecules, protecting them from moisture while maintaining the stability and reproducibility benefits of the amorphous state. The carriers act as mediators that prevent direct interaction between linagliptin and environmental moisture.
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 solid dispersion is stable, reproducible, and non-hygroscopic, making it suitable for formulating linagliptin, enhancing its pharmaceutical properties and suitability for various pharmaceutical forms.
Implementation Method 1
preparing a solution comprising a mixture of linagliptin and one or more pharmaceutically acceptable carriers selected from copovidone, ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol or soluplus in a solvent; and removing the solvent to obtain amorphous solid dispersion of linagliptin
Data Source
AI summary
The present invention provides a novel amorphous solid dispersion of linagliptin in combination with a pharmaceutically acceptable carrier, process for its preparation and pharmaceutical compositions comprising it.