Rufinamide Solid Dispersion for Polymorphic Stability
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Solution Overview
Problem
Rufinamide, an anticonvulsant medication, exhibits polymorphism which affects its stability, dissolution rate, and physical properties, making it challenging to develop a stable and reproducible pharmaceutical form suitable for large-scale production.
Innovation Solution
A solid dispersion of rufinamide is created in combination with pharmaceutically acceptable carriers such as copovidone, SPAN®20, ethyl cellulose, hydroxypropyl methylcellulose, or polyethylene glycol, using a process involving the preparation of a solution with these carriers in a solvent and subsequent solvent removal to obtain a stable solid dispersion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If rufinamide is formulated in conventional crystalline forms, then the drug can be manufactured, but the polymorphism causes variability in stability, dissolution rate, and physical properties
Solution Approach 1:
The patent transforms rufinamide from a crystalline state to an amorphous state by incorporating it into a solid dispersion matrix. This parameter change in physical state eliminates polymorphic variability while maintaining manufacturing feasibility, directly addressing the contradiction between stability and reproducibility
Solution Approach 2:
The patent creates a composite solid dispersion system combining rufinamide with excipients such as hydroxypropyl methylcellulose and polyethylene glycol. This composite approach stabilizes the amorphous drug form and ensures consistent physical properties across batches, resolving the contradiction between stability and manufacturing precision
2Adaptability or versatility
If multiple polymorphic forms are possible, then the drug has versatile physical forms, but it becomes difficult to determine which form to use for consistent pharmaceutical performance
Solution Approach 1:
The patent extracts rufinamide from its crystalline polymorphic forms and incorporates it into an amorphous solid dispersion matrix. This extraction eliminates the polymorphism problem entirely, providing a single versatile formulation approach that simplifies manufacturing while maintaining adaptability
Solution Approach 2:
By changing the physical state parameter from crystalline to amorphous, the patent creates a single versatile formulation platform that can be manufactured consistently without dealing with multiple polymorphic forms, thus improving ease of manufacture while preserving adaptability
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 resulting solid dispersion is stable, reproducible, and amenable to large-scale preparation, enhancing the pharmaceutical form's stability and processing characteristics.
Implementation Method 1
preparing a solution comprising a mixture of rufinamide and one or more pharmaceutically acceptable carriers selected from copovidone, SPAN®20 (sorbitan laurate), ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol or SOLUPLUS® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) in a solvent
Implementation Method 2
removing the solvent from the solution to obtain a solid dispersion of rufinamide in combination with a pharmaceutically acceptable carrier
Data Source
AI summary
The present invention provides a solid dispersion of rufinamide in combination with a pharmaceutically acceptable carrier, process for its preparation and pharmaceutical compositions comprising it.