Aqueous Ticagrelor Solutions Using Cyclodextrin for Storage Stability
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Solution Overview
Problem
Existing ticagrelor formulations face challenges with degradation due to light, heat, and oxygen susceptibility, and limited solubility, making it difficult to develop stable aqueous solutions suitable for emergency use and long-term storage.
Innovation Solution
An aqueous ticagrelor solution stabilized with cyclodextrin or vitamin E TPGS, forming a water-soluble inclusion complex with ticagrelor, maintaining stability for at least 3 months under accelerated conditions and providing improved solubility without the use of organic co-solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If ticagrelor is formulated as an aqueous solution, then solubility and bioavailability are improved, but stability against degradation by light, heat, and oxygen deteriorates
Solution Approach 1:
The patent employs cyclodextrins as intermediary host molecules that form inclusion complexes with ticagrelor. The cyclodextrin cavity encapsulates the ticagrelor molecule, protecting it from degradation by light, heat, and oxygen while simultaneously enhancing its solubility in aqueous media. This mediator approach resolves the contradiction by providing both solubility enhancement and stability protection simultaneously.
Solution Approach 2:
The invention creates a composite pharmaceutical formulation consisting of ticagrelor incorporated within cyclodextrin inclusion complexes. This composite structure combines the benefits of both components: the ticagrelor provides the therapeutic antiplatelet activity while the cyclodextrin matrix provides enhanced solubility and improved stability against environmental degradation factors.
2Loss of time
If ticagrelor is prepared as a ready-to-use liquid formulation, then treatment time in emergency situations is reduced, but manufacturing complexity increases due to stability requirements
Solution Approach 1:
The patent applies preliminary action by pre-formulating ticagrelor in stable cyclodextrin inclusion complexes during manufacturing. This preliminary stabilization allows the formulation to be prepared in advance and stored ready-to-use without degradation, eliminating the need for last-minute preparation in emergency situations while maintaining manufacturing feasibility through established cyclodextrin complexation techniques.
3Quantity of substance
If organic co-solvents are used to improve ticagrelor solubility, then bioavailability increases, but safety and regulatory acceptance deteriorate
Solution Approach 1:
The invention changes the solubility parameter by transitioning from organic co-solvent systems to an aqueous-based cyclodextrin inclusion complex system. This parameter change achieves the same solubility enhancement goal but through a safer, more regulatory-friendly mechanism that avoids organic solvents entirely, thereby improving both solubility and safety simultaneously.
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 solution offers a stable, ready-to-use ticagrelor formulation suitable for intravenous administration, ensuring effective treatment in emergency situations and improving bioavailability for patients with ticagrelor-responsive conditions.
Implementation Method 1
An aqueous ticagrelor solution stabilized with cyclodextrin or vitamin E TPGS, forming a water-soluble inclusion complex with ticagrelor
Implementation Method 2
Ticagrelor has shown to be highly susceptible to degradation when exposed to light, heat and oxygen
Data Source
AI summary
The present invention provides an aqueous ticagrelor composition with improved storage stability comprising ticagrelor as active ingredient and a solubilizer for ticagrelor, preferably a cyclodextrin or vitamin E TPGS. The aqueous ticagrelor solution is preferably provided for intravenous administration, either by injection or infusion. Preferably an aqueous ticagrelor intravenous composition according to the invention, in a ready-to-use form or suitable for dilution prior to intravenous administration, is used as a medicine in the treatment of a ticagrelor responsive disease.