Isoproterenol Aqueous Composition for Oxidation-Stable Injection
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Solution Overview
Problem
Existing isoproterenol compositions are unstable due to susceptibility to oxidation, isomerization, and nucleophilic reactions, making them unsuitable for ready-to-administer formulations.
Innovation Solution
Formulations with isoproterenol in a buffered aqueous solution at pH 3.0-4.5, containing a chelating agent like EDTA and tonicity agent like NaCl, packaged with a non-contact oxygen absorber, and terminally sterilized to maintain stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If isoproterenol is formulated in aqueous solution for ready-to-administer use, then ease of operation is improved, but chemical stability deteriorates due to oxidation and degradation
Solution Approach 1:
The patent applies parameter changes by optimizing pH to range 3.0-4.5 and controlling buffer concentration at 10mM or less, which stabilizes isoproterenol against oxidation and degradation while maintaining aqueous solubility for ready-to-administer use. This resolves the contradiction by finding optimal parameter values that satisfy both ease of operation and chemical stability.
Solution Approach 2:
The patent introduces EDTA as a chelating agent that acts as an intermediary to bind metal ions that would otherwise catalyze oxidation of isoproterenol. This mediator protects the active ingredient while maintaining the aqueous formulation, resolving the contradiction between ease of operation and chemical stability.
2Stability of the object's composition
If antioxidants are added to stabilize isoproterenol, then chemical stability is improved, but product purity deteriorates due to formation of degradation impurities
Solution Approach 1:
The patent takes out traditional antioxidants from the formulation and replaces them with a chelating agent (EDTA) that stabilizes isoproterenol through a different mechanism. This extraction of harmful antioxidants while maintaining stabilization resolves the contradiction between chemical stability and product purity.
Solution Approach 2:
EDTA serves as an intermediary chelating agent that binds metal ions without forming degradation impurities, unlike traditional antioxidants. This mediator provides chemical stability while maintaining product purity, resolving the technical contradiction.
3Temperature
If buffer concentration is increased to maintain pH stability, then pH control is improved, but isoproterenol degradation increases due to nucleophilic reactions
Solution Approach 1:
The patent applies parameter changes by limiting buffer concentration to 10mM or less while maintaining pH in the 3.0-4.5 range. This optimized parameter combination provides sufficient pH control while minimizing nucleophilic degradation, resolving the contradiction between pH stability and degradation resistance.
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 formulations exhibit less than 3% impurities after two weeks at 60°C, maintaining stability for extended periods without substantial degradation or enantiomeric change.
Implementation Method 1
formulations with isoproterenol in a buffered aqueous solution at pH 3.0-4.5, containing a chelating agent like EDTA
Implementation Method 2
packaged with a non-contact oxygen absorber
Implementation Method 3
isoproterenol in a buffered aqueous solution at pH 3.0-4.5
Data Source
AI summary
Storage stable aqueous ready-to-administer formulations comprising isoproterenol are presented with desirable stability characteristics. In preferred aspects, formulations are terminally sterilized and packaged in a suitable format, such as a polymeric bag with metalized overwrap and include a non-contact oxygen scavenger.