Epinephrine Formulation Stabilization via pH Adjustment
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Solution Overview
Problem
Current epinephrine-containing pharmaceutical compositions, such as Adrenalin®, have limited shelf life due to the formation of degradants like epinephrine sulfonic acid and D-epinephrine, leading to high impurity levels and reduced therapeutic effectiveness over time.
Innovation Solution
A pharmaceutical composition comprising epinephrine with added pH-raising agents, antioxidants, transition metal complexing agents, and tonicity regulators to stabilize the solution, reduce degradant formation, and maintain low impurity levels, allowing for extended shelf life and improved stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If epinephrine is stored in conventional pharmaceutical compositions, then it provides immediate therapeutic availability, but it forms degradants (epinephrine sulfonic acid and D-epinephrine) that limit shelf life to 14-18 months
Solution Approach 1:
The patent introduces pH-raising agents (such as sodium hydroxide, potassium hydroxide, or ammonia) as intermediary substances that mediate between the epinephrine and degradant formation. These intermediaries raise the pH to 6.0-9.0, creating a chemical environment that suppresses the formation of epinephrine sulfonic acid and D-epinephrine, thereby extending shelf life while maintaining therapeutic effectiveness.
Solution Approach 2:
The patent changes the pH parameter of the pharmaceutical composition from the conventional acidic range (2.2-5.0) to a higher range (6.0-9.0). This parameter change fundamentally alters the chemical stability profile of epinephrine, reducing degradant formation rates and extending shelf life from 14-18 months to potentially 2-3 years or longer, while maintaining therapeutic effectiveness through proper formulation.
2Duration of action of stationary object
If pH is raised to reduce degradant formation, then shelf life is extended, but epinephrine solubility and stability may be compromised
Solution Approach 1:
The patent creates a composite pharmaceutical composition that combines epinephrine with multiple stabilizing agents including pH-raising agents, antioxidants (such as ascorbic acid, sodium metabisulfite, or propyl gallate), and chelating agents (such as EDTA). This composite formulation works synergistically to maintain epinephrine stability at elevated pH levels, preventing oxidation and metal-catalyzed degradation while extending shelf life.
Solution Approach 2:
The patent applies preliminary protective actions by incorporating antioxidants and chelating agents into the formulation before storage. These agents preemptively prevent oxidative degradation and metal-catalyzed decomposition, allowing the composition to maintain epinephrine stability at higher pH levels throughout the extended shelf life period.
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 effectively reduces the levels of D-epinephrine, epinephrine sulfonic acid, and oxidative degradants, maintaining therapeutic efficacy and stability over a longer period, thereby extending the shelf life and ensuring consistent performance.
Implementation Method 1
The composition may comprise an antioxidant... reduces the levels of D-epinephrine, epinephrine sulfonic acid, and oxidative degradants
Implementation Method 2
A pharmaceutical composition comprising epinephrine with added pH-raising agents... to stabilize the solution, reduce degradant formation
Implementation Method 3
A pharmaceutical composition comprising epinephrine with added... transition metal complexing agents... to stabilize the solution
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.