Ready-to-Use Bivalirudin Composition Stabilization
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Solution Overview
Problem
Bivalirudin, a crucial anticoagulant for percutaneous coronary intervention, is currently available only as a lyophilized form that requires reconstitution, leading to suboptimal dosing and increased risk of calculation and dilution errors, which can result in decreased efficacy and safety during cardiovascular procedures.
Innovation Solution
A ready-to-use (RTU) bivalirudin composition is developed by mixing bivalirudin with stabilizing agents such as buffering agents, pH-adjusting agents, polymers, preservatives, antioxidants, sugars, or polyols to maintain a pH of about 4 to less than 5, which stabilizes the drug and reduces impurity formation, thereby eliminating the need for reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If bivalirudin is provided as a lyophilized form requiring reconstitution, then storage stability is improved, but dosing accuracy and safety are worsened due to calculation and dilution errors
Solution Approach 1:
The patent applies preliminary action by pre-reconstituting bivalirudin to a target concentration (e.g., 5 mg/mL) and stabilizing it with buffering agents before final use. This eliminates the need for healthcare providers to perform reconstitution and dilution calculations, thereby preventing dosing errors while maintaining stability through pre-established formulation conditions.
Solution Approach 2:
The patent changes the physical and chemical parameters of bivalirudin by adjusting pH to a specific range (pH 4.0-5.0) using buffering agents and stabilizing agents. This parameter optimization enables the drug to remain stable as a ready-to-use liquid solution without requiring reconstitution, thus improving both storage stability and dosing accuracy simultaneously.
2Manufacturing precision
If bivalirudin is formulated as a ready-to-use composition with stabilizing agents, then dosing accuracy is improved by eliminating reconstitution errors, but formulation complexity increases
Solution Approach 1:
The patent applies universality by using multi-functional stabilizing agents that simultaneously perform multiple functions: buffering agents maintain pH within the optimal range (pH 4.0-5.0), antioxidants prevent oxidation degradation, and stabilizing agents prevent aggregation. This multi-functionality approach achieves dosing accuracy through pre-prepared formulations while managing formulation complexity through consolidated ingredient roles.
3Ease of operation
If bivalirudin is stored as a liquid solution, then ease of administration is improved, but stability deteriorates due to degradation over time
Solution Approach 1:
The patent introduces intermediary substances (stabilizing agents, buffering agents, antioxidants) that mediate between bivalirudin and the environment. These intermediaries protect bivalirudin from degradation mechanisms such as oxidation, hydrolysis, and aggregation, enabling the drug to maintain stability as a liquid solution over extended periods while remaining easy to administer without reconstitution.
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 RTU bivalirudin composition ensures stable bivalirudin levels with reduced impurities, enhancing its stability and efficacy, reducing the risk of dosing errors, and improving the efficiency of cardiovascular procedures by providing a more straightforward and reliable administration method.
Implementation Method 1
the one or more stabilizing agents may be buffering agents, pH-adjusting agents
Implementation Method 2
adjusting the pH to about 4 to less than 5
Data Source
AI summary
Ready-to-use bivalirudin compositions, methods of using the ready-to-use bivalirudin compositions, and methods of preparing the ready-to-use bivalirudin compositions. The ready-to-use bivalirudin compositions comprise bivalirudin and one or more stabilizing agents. The one or more stabilizing agents may be buffering agents having a pKa of about 2.5 to about 6.5, pH-adjusting agents, polymers, preservatives, antioxidants, sugars or polyols, or a combination thereof. The ready-to-use bivalirudin compositions may also comprise [9-10]-cycloimido bivalirudin, [11-12]-cycloimido bivalirudin, or a combination thereof. The method of using the ready-to-use bivalirudin compositions comprises administering the ready-to-use compositions to a patient in need thereof. Further, the method of preparing the ready-to-use bivalirudin compositions comprises mixing bivalirudin with one or more stabilizing agents.