Epinephrine Compositions With Chelation for Impurity Reduction
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Solution Overview
Problem
Current epinephrine-containing pharmaceutical compositions have limited shelf life due to the formation of degradants such as epinephrine sulfonic acid (ESA) and D-epinephrine, leading to increased impurity levels and reduced effectiveness over time.
Innovation Solution
A pharmaceutical composition comprising epinephrine with additives such as pH raising agents, antioxidants, transition metal complexing agents, pH lowering agents, and tonicity regulating agents to stabilize the formulation and reduce impurity formation, including low levels of D-epinephrine and oxidative degradants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If epinephrine is stored in conventional pharmaceutical compositions, then it provides therapeutic benefits, but it forms degradants (ESA and D-epinephrine) that increase impurity levels and reduce effectiveness over time
Solution Approach 1:
The patent introduces antioxidants (such as ascorbic acid, sodium bisulfite, or sodium metabisulfite) as intermediary substances that mediate between epinephrine and oxidative degradation. These antioxidants preferentially react with oxygen and other oxidizing agents, protecting epinephrine from forming degradants like ESA and D-epinephrine, thereby maintaining both stability and therapeutic effectiveness
Solution Approach 2:
The patent modifies the chemical environment parameters of the pharmaceutical composition by adjusting pH levels (using buffers like phosphate buffer or citrate buffer) and controlling redox potential. These parameter changes create conditions that minimize epinephrine degradation while maintaining its therapeutic activity, resolving the contradiction between stability and effectiveness
2Duration of action of stationary object
If epinephrine formulations are extended in shelf life, then storage time increases, but impurity levels increase and effectiveness decreases
Solution Approach 1:
The patent applies preliminary protective actions during formulation by incorporating antioxidants, chelating agents (like EDTA), and buffer systems before storage begins. These pre-installed protective mechanisms actively prevent degradant formation throughout the extended shelf life, allowing the product to maintain low impurity levels (<20% total impurities) even after prolonged storage
Solution Approach 2:
The patent ensures continuous protective action through the inclusion of multiple stabilizing components that work synergistically throughout the entire shelf life. The antioxidants continuously scavenge oxidants, buffers continuously maintain pH, and chelating agents continuously bind metal ions, creating an ongoing protective environment that prevents impurity accumulation over time
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 composition maintains stability and reduces impurity levels, extending shelf life and ensuring effective treatment of allergic reactions and other medical conditions while minimizing adverse effects.
Implementation Method 1
Shelf life is limited by the formation of degradants, which mainly comprise epinephrine sulfonic acid (ESA) and D-epinephrine
Implementation Method 2
hydrochloric acid to adjust pH
Implementation Method 3
transition metal complexing agents to stabilize the formulation
Data Source
AI summary
Pharmaceutical compositions comprising epinephrine, methods of administration, and methods of making the same. Compositions may comprise at least one of an active agent, a pH raising agent, an antioxidant, a transition metal complexing agent, a pH lowering agent, a tonicity regulating agent, optionally a preservative, and optionally a solvent.