Buffered Selatogrel Aqueous Composition for pH Stability
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Solution Overview
Problem
Existing aqueous solutions of the P2Y12 receptor antagonist selatogrel are not stable enough for subcutaneous administration, leading to degradation and potential loss of efficacy due to pH fluctuations during storage.
Innovation Solution
Stabilizing the aqueous solution of selatogrel by buffering it to a pH value of 8.2 or above using pharmaceutically acceptable buffers like boric acid or arginine, ensuring stability for at least 12 months, especially at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If an aqueous solution of selatogrel is prepared for subcutaneous administration, then rapid pharmacodynamic effect is achieved, but the solution becomes unstable and degrades during storage
Solution Approach 1:
The patent changes the pH parameter of the aqueous solution to a basic range (pH 8.0-10.0, preferably pH 8.5-9.5) to stabilize selatogrel. This parameter modification prevents degradation while maintaining the compound's ability to rapidly inhibit platelet aggregation after subcutaneous administration
2Stability of the object's composition
If the pH of the aqueous solution is adjusted to stabilize selatogrel, then storage stability is improved, but the solution may cause local tissue irritation or alter drug distribution
Solution Approach 1:
The patent uses buffering agents (such as phosphate buffer, citrate buffer, or carbonate buffer) as intermediaries to maintain the basic pH environment. These buffers act as mediators that stabilize the solution pH without causing excessive alkalinity, thereby preventing tissue irritation while maintaining drug stability
Solution Approach 2:
The patent optimizes the pH parameter to a specific basic range (pH 8.0-10.0) that balances stability with biocompatibility. This controlled parameter change ensures the solution remains stable during storage while minimizing harmful effects on tissues upon administration
3Stability of the object's composition
If buffers are added to stabilize the aqueous solution, then pH control and stability are improved, but the formulation complexity increases
Solution Approach 1:
The patent employs buffering agents that serve multiple functions: they maintain pH stability, prevent selatogrel degradation, and ensure biocompatibility upon administration. This multi-functionality reduces the need for additional separate stabilization components, thereby limiting the increase in formulation complexity
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 buffered solution maintains selatogrel's stability and effectiveness, allowing for rapid pharmacodynamic effects, such as over 85% inhibition of platelet aggregation within 15 minutes post-administration, without significant degradation.
Implementation Method 1
Stabilizing the aqueous solution of selatogrel by buffering it to a pH value of 8.2 or above using pharmaceutically acceptable buffers like boric acid or arginine
Data Source
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AI summary
The present invention relates to an aqueous pharmaceutical composition comprising the P2Y12 receptor antagonist 4-((R)-2-{[6-((S)-3-methoxy-pyrrolidin-1-yl)-2-phenyl- pyrimidine-4-carbonyl]-amino}-3-phosphono-propionyl)-piperazine-1-carboxylic acid butyl ester and a pharmaceutically acceptable buffer and its use as a medicament by parenteral administration.