Amorphous NSAID Melt Extrudate Stabilization
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Solution Overview
Problem
The amorphous form of pharmaceutical ingredients, such as NSAIDs, is not stable enough for use in commercial products, leading to inconsistent or slow dissolution profiles, which necessitates the inclusion of dissolution aids that increase costs and complexity.
Innovation Solution
A solidified melt extrudate comprising an active pharmaceutical ingredient in an amorphous form combined with a specific blend of polymers, including dimethylaminoethyl methacrylate co-polymer and polyvinylpyrrolidone-vinyl acetate co-polymer, which provides stability and inhibits precipitation, allowing for consistent and rapid drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If the amorphous form of NSAID is used, then solubility and dissolution rate are improved, but physical stability deteriorates
Solution Approach 1:
The patent uses a composite material system consisting of amorphous NSAID combined with a specific polymer blend (hydrophobic polymer like Eudragit E PO and hydrophilic polymer like PVP VA 64). This composite structure allows the amorphous drug to maintain high solubility and dissolution rate while the polymer matrix provides physical stability and prevents crystallization, thus resolving the contradiction between dissolution speed and physical stability
Solution Approach 2:
The patent changes the physical state parameter of the NSAID from crystalline to amorphous form, and simultaneously modifies the chemical environment by introducing a specific polymer blend system. This parameter change enables the drug to achieve both rapid dissolution (through amorphous state) and long-term stability (through polymer stabilization), resolving the inherent contradiction
2Stability of the object's composition
If crystalline form of NSAID is used, then stability is improved, but solubility and dissolution rate deteriorate
Solution Approach 1:
The patent fundamentally changes the physical state parameter of the NSAID from crystalline to amorphous form. This parameter change transforms the drug's properties to achieve both rapid dissolution (characteristic of amorphous form) and long-term stability (provided by the polymer matrix), thereby resolving the contradiction between stability and dissolution rate
3Speed
If dissolution aids are added to improve dissolution profile, then dissolution rate is improved, but formulation complexity and cost increase
Solution Approach 1:
The polymer blend serves multiple functions simultaneously: it acts as a stabilizer to prevent crystallization, a dissolution enhancer to maintain rapid dissolution rate, and a structural matrix to hold the amorphous drug. This multi-functionality eliminates the need for separate dissolution aids, reducing formulation complexity while maintaining fast dissolution
Solution Approach 2:
The patent creates a composite material where the polymer blend and amorphous NSAID work together as an integrated system. The specific combination of hydrophobic and hydrophilic polymers provides both stabilization and dissolution enhancement in a single formulation approach, avoiding the need for multiple separate additives and simplifying the overall formulation
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 polymer blend stabilizes the amorphous form of the active ingredient, ensuring consistent and rapid drug release without the need for additional dissolution aids, thereby reducing costs and complexity while maintaining stability for at least six months.
Implementation Method 1
the amorphous form of an active pharmaceutical ingredient is a less stable form than the crystalline form of the same compound
Implementation Method 2
Physical stability of an amorphous drug in a polymeric carrier depends on factors such as intermolecular interactions
Implementation Method 3
solidified melt extrudate comprising an active pharmaceutical ingredient in an amorphous form
Implementation Method 4
The extrusion process transforms the polymer and active ingredient mixture from solid to molten state and then back to solidified amorphous form
Data Source
AI summary
A solidified melt extrudate comprising an active pharmaceutical ingredient in an amorphous form and a combination of at least two polymers.