Prasugrel Cyclodextrin Inclusion Complex for Bioavailability
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Solution Overview
Problem
Current prasugrel therapies for acute coronary syndromes face limitations such as inter-individual variability in platelet inhibition, slow onset of action, and increased risk of bleeding, particularly in certain patient subgroups, indicating a need for a formulation that can be titrated more safely and effectively with improved bioavailability and therapeutic onset.
Innovation Solution
A pharmaceutical composition comprising prasugrel and a cyclodextrin derivative, specifically formulated to enhance bioavailability and titratability, with a cyclodextrin derivative concentration ranging from 100:1 to 8000:1 by weight relative to prasugrel, and pH adjustments between 2 to 9, to improve the solubility and stability of prasugrel, allowing for more efficient platelet inhibition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard prasugrel therapy is used, then platelet inhibition is achieved, but inter-individual variability in platelet inhibition occurs and onset of action is slow
Solution Approach 1:
The patent introduces a cyclodextrin derivative as an intermediary substance that forms an inclusion complex with prasugrel. This complex acts as a mediator that enhances the solubility and bioavailability of prasugrel, leading to more consistent platelet inhibition and faster onset of action. The cyclodextrin derivative serves as the intermediary that resolves the variability and delay issues in standard prasugrel therapy.
Solution Approach 2:
The patent changes the physical and chemical parameters of prasugrel by forming an inclusion complex with cyclodextrin derivative. This complexation alters the solubility, dissolution rate, and bioavailability parameters of prasugrel, resulting in improved platelet inhibition consistency and reduced onset time. The parameter changes are achieved through the molecular-level interaction between cyclodextrin and prasugrel.
2Reliability
If higher doses of prasugrel are administered to improve platelet inhibition, then platelet inhibition levels increase, but risk of bleeding increases
Solution Approach 1:
The cyclodextrin derivative acts as a bioavailability enhancer that allows achieving therapeutic platelet inhibition at lower prasugrel doses. By improving the drug's absorption and metabolism, the intermediary reduces the need for high dosing, thereby lowering bleeding risk while maintaining effective platelet inhibition.
Solution Approach 2:
The inclusion complex changes the pharmacokinetic parameters of prasugrel, specifically improving bioavailability and reducing clearance. This allows the same therapeutic effect to be achieved at lower doses, shifting the dose-response relationship and reducing the harmful bleeding effect associated with high dosing.
3Speed
If prasugrel is formulated with cyclodextrin derivative to enhance bioavailability, then therapeutic onset speeds up, but formulation complexity increases
Solution Approach 1:
The cyclodextrin derivative is introduced as a simple intermediary molecule that forms an inclusion complex with prasugrel. Despite adding a component, the overall formulation remains relatively simple, avoiding excessive complexity while achieving significant speed-up in therapeutic onset through improved bioavailability.
Solution Approach 2:
The patent creates a composite material system consisting of cyclodextrin derivative and prasugrel in an inclusion complex. This composite approach enhances the therapeutic properties of prasugrel without requiring complex multi-component formulations or sophisticated delivery systems, maintaining formulation simplicity while achieving fast onset.
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 prasugrel-cyclodextrin composition provides enhanced bioavailability and a faster therapeutic onset, reducing adverse bleeding events and improving clinical outcomes by achieving consistent platelet inhibition, particularly in high-risk patient populations.
Implementation Method 1
compositions comprising prasugrel and a cyclodextrin derivative... enhance bioavailability... improve the solubility and stability of prasugrel
Data Source
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AI summary
The present invention is directed to pharmaceutical compositions comprising prasugrel and a cyclodextrin derivative, and methods of making and using the same.