Liquid Bivalirudin Composition With pH-Controlled Shelf Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing bivalirudin formulations require reconstitution and have short shelf-lives, leading to dosing errors and instability, especially when stored at refrigerated conditions.
Innovation Solution
Development of ready-to-use liquid bivalirudin compositions with pH ranging from about 3.0 to less than 4.0 or 5.0 to 5.7, containing tonicity-adjusting and stabilizing agents, providing at least 6-month shelf life at refrigerated conditions, with reduced impurity levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If bivalirudin is formulated as a lyophilized drug product requiring reconstitution, then storage stability is improved, but ease of operation deteriorates due to multiple preparation steps and risk of dosing errors
Solution Approach 1:
The patent changes the physical state parameter from lyophilized powder to liquid formulation, and adjusts pH parameters to specific ranges (3.0-4.0 or 5.0-5.7) to achieve both storage stability and ready-to-use convenience. This eliminates the reconstitution step while maintaining stability through controlled pH and formulation composition.
2Ease of operation
If bivalirudin is formulated with pH 4.0-5.0 to be ready-to-use, then ease of operation is improved, but stability deteriorates due to extensive degradation after one month storage
Solution Approach 1:
The patent identifies two distinct pH ranges (3.0-4.0 and 5.0-5.7) where bivalirudin remains stable for extended periods. By changing the pH parameter to these specific ranges and adjusting formulation composition including buffer systems and excipients, the patent achieves both ready-to-use convenience and long-term storage stability, resolving the degradation issue at pH 4.0-5.0.
3Stability of the object's composition
If bivalirudin is stored at refrigerated conditions, then stability is improved, but shelf life is limited to only a few hours after reconstitution
Solution Approach 1:
The patent changes the formulation composition parameters including pH, buffer capacity, and excipient types to enable long-term stability at refrigerated temperatures. The liquid formulation with specific pH ranges and stabilizing components maintains potency for extended periods (months rather than hours) when stored at 2-8°C, significantly extending the usable shelf life.
4Manufacturing precision
If multiple reconstitution and dilution steps are performed, then correct dosing is achieved, but manufacturing precision deteriorates due to incomplete dissolution and dosing errors
Solution Approach 1:
The patent extracts and eliminates the reconstitution and dilution steps from the administration process. By providing a ready-to-use liquid formulation with predetermined concentration and volume, the patent removes the complex multi-step preparation process while ensuring dosing accuracy, thereby improving manufacturing precision and reducing preparation complexity.
Data Source
AI summary
Ready-to-use liquid bivalirudin compositions, methods of using the ready-to-use bivalirudin compositions, and methods of preparing the ready-to-use liquid bivalirudin compositions are provided herein. The liquid ready-to-use bivalirudin compositions comprise a pharmaceutically acceptable amount of bivalirudin.