Epinephrine Formulation Stabilization for Longer Shelf Life
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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 impurities, including low levels of D-epinephrine and epinephrine sulfonic acid, while maintaining pH stability over shelf life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If epinephrine is formulated in conventional pharmaceutical compositions, then it provides immediate therapeutic effect for emergency treatments, but it forms degradants such as epinephrine sulfonic acid and D-epinephrine that limit shelf life to 18 months or less
Solution Approach 1:
The patent changes the pH parameter of the formulation by adding pH raising agents (such as sodium hydroxide, potassium hydroxide, or ammonium hydroxide) to maintain pH above 3.0, which slows the degradation of epinephrine and extends shelf life beyond 18 months while maintaining therapeutic effectiveness
Solution Approach 2:
The patent introduces intermediary substances including antioxidants (such as ascorbic acid, sodium metabisulfite, or propyl gallate) and transition metal complexing agents (such as EDTA or citric acid) that mediate between epinephrine and degradative processes, protecting the active ingredient from oxidation and metal-catalyzed degradation
2Manufacturing precision
If conventional epinephrine formulations are used, then they meet initial purity requirements, but impurity levels increase over time due to degradant formation
Solution Approach 1:
The patent applies preliminary protective actions by incorporating antioxidants and metal complexing agents into the formulation before storage, which preemptively prevent oxidative and metal-catalyzed degradation pathways, maintaining compositional stability and low impurity levels throughout the extended shelf life
Solution Approach 2:
The patent modifies the chemical environment parameters by adjusting pH to above 3.0 and adding stabilizing agents, which changes the degradation kinetics and maintains compositional stability over time, preventing the increase in impurity levels that would otherwise occur
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 achieves reduced impurity levels, prolonged shelf life, and improved stability by inhibiting the formation of oxidative degradants and maintaining pH within a stable range, ensuring effective use in emergency medical treatments and surgical applications.
Implementation Method 1
Shelf life is limited by the formation of degradants, which mainly comprise epinephrine sulfonic acid (ESA)
Implementation Method 2
The pH range of Adrenalin® is 2.2-5.0... 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 impurities, including low levels of D-epinephrine and epinephrine sulfonic acid, while maintaining pH stability over shelf life
Implementation Method 3
comprising epinephrine with additives such as pH raising agents, antioxidants, transition metal complexing agents
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.