Amorphous Prasugrel Solubility and Oxidative Stability
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Solution Overview
Problem
Prasugrel, an orally administered platelet aggregation inhibitor, has limited solubility and is prone to oxidative degradation, which restricts its bioavailability and stability, especially when processed into pharmaceutical compositions.
Innovation Solution
Transforming prasugrel into a non-crystalline form, either as an amorphous solid or solid dispersion with a hydrophilic polymer, stabilizes the metastable state and enhances solubility and stability, allowing for improved bioavailability and processing into pharmaceutical compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If prasugrel is micronized to increase solubility, then solubility is improved, but oxidative degradation increases due to increased surface area
Solution Approach 1:
The patent changes the physical state parameter of prasugrel from crystalline to non-crystalline (amorphous) form. This parameter change increases solubility while the non-crystalline structure provides better protection against oxidative degradation compared to micronized crystalline forms, resolving the contradiction between solubility improvement and degradation increase.
Solution Approach 2:
The patent creates a composite system by combining prasugrel with hydrophilic polymers to form solid dispersions. This composite approach enhances solubility through the hydrophilic polymer matrix while the polymer coating protects the active substance from oxidative degradation, simultaneously addressing both improvements.
2Quantity of substance
If prasugrel is processed into pharmaceutical compositions, then bioavailability is improved, but chemical stability decreases
Solution Approach 1:
The patent changes the physical state of prasugrel from crystalline to non-crystalline form, which improves bioavailability while maintaining chemical stability. The non-crystalline structure has higher solubility and faster dissolution rates without the oxidative degradation issues that plague micronized crystalline forms.
Solution Approach 2:
The patent introduces hydrophilic polymers as intermediary substances that form solid dispersions with prasugrel. These polymers act as protectors that enhance bioavailability through improved solubility and dissolution while simultaneously protecting the active substance from chemical degradation during processing and storage.
3Ease of manufacture
If crystalline prasugrel is used, then manufacturing is simpler, but solubility is limited
Solution Approach 1:
The patent changes the physical state parameter from crystalline to non-crystalline form. This transformation significantly improves solubility while the manufacturing process remains relatively simple through techniques like spray drying, freeze drying, or co-extrusion methods that can be integrated into existing pharmaceutical manufacturing lines.
Solution Approach 2:
The patent utilizes phase transition techniques to transform crystalline prasugrel into non-crystalline form. Methods include rapid cooling from melt, spray drying, freeze drying, or extrusion processes that induce amorphization. These phase transition approaches improve solubility while maintaining manufacturing feasibility through established industrial techniques.
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 non-crystalline form of prasugrel significantly increases solubility and bioavailability, stabilizes the active substance against oxidative degradation, and improves the processing and shelf life of pharmaceutical compositions.
Implementation Method 1
Prasugrel in non-crystalline form... significantly increases solubility and bioavailability
Implementation Method 2
stabilizes the active substance against oxidative degradation
Data Source
AI summary
The present invention relates to prasugrel or a pharmaceutically compatible salt thereof, compositions that contain this active substance and pharmaceutical compositions that contain this active substance or a composition containing this active substance. The present invention further relates to methods for producing the novel compositions.