Epinephrine Liquid Formulation pH Tuning for Room-Temperature Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for improved liquid, injectable formulations of epinephrine that are storage stable for longer durations at room temperature.
Innovation Solution
A pharmaceutical formulation comprising epinephrine or a pharmaceutically acceptable salt thereof, an organic acid, and water, with a pH of from about 3.0 to about 3.6 and substantially free of a conjugate base of the organic acid, which is stable and has a shelf life of at least about 12 months.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If conventional epinephrine formulations with pH 2.2-5.0 and multiple excipients are used, then the formulation is stable for storage, but the shelf life is limited to 15-24 months and requires refrigeration or controlled temperature storage
Solution Approach 1:
The patent optimizes the pH parameter to a specific range of 3.0-3.6 and controls the concentration of the organic acid buffer system to achieve enhanced stability. This parameter optimization allows the formulation to maintain stability at room temperature (20-25°C) for at least 24 months, eliminating the need for refrigeration while extending shelf life beyond conventional formulations.
2Stability of the object's composition
If conventional epinephrine formulations with multiple excipients including antioxidants and preservatives are used, then the formulation maintains stability, but impurities accumulate over time and require complex formulation composition
Solution Approach 1:
The patent eliminates conventional antioxidants (sulfites, metabisulfites) and preservatives from the formulation. By removing these excipients and relying on the optimized pH 3.0-3.6 buffer system, the formulation achieves stability without the harmful impurities that accumulate from degradation of these additives, resulting in a cleaner product with fewer harmful byproducts.
Solution Approach 2:
The patent changes the chemical environment by optimizing pH to 3.0-3.6 and using an organic acid buffer system, which creates conditions that prevent epinephrine degradation without requiring traditional antioxidants. This parameter optimization reduces impurity formation while maintaining formulation stability throughout the shelf life.
3Quantity of substance
If epinephrine concentration is maintained at 1 mg/mL with conventional excipients, then the formulation is ready for injection, but storage stability degrades over time and requires multiple excipients
Solution Approach 1:
The patent maintains the clinically relevant epinephrine concentration of 1 mg/mL while optimizing the pH parameter to 3.0-3.6 and using an organic acid buffer system. This parameter optimization enables the formulation to remain stable at room temperature for at least 24 months, significantly extending storage stability duration compared to conventional formulations without requiring additional excipients.
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 formulation maintains stability and effectiveness with minimal impurities, retaining at least 90% of the labeled epinephrine concentration and less than 10% impurities after storage under room and accelerated conditions, ensuring safety and efficacy for extended periods.
Implementation Method 1
A pharmaceutical formulation comprising epinephrine or a pharmaceutically acceptable salt thereof, an organic acid, and water, with a pH of from about 3.0 to about 3.6 and substantially free of a conjugate base of the organic acid
Data Source
AI summary
The invention provides a stable, pharmaceutical formulation comprising epinephrine or a pharmaceutically acceptable salt thereof. The formulation includes an organic acid, a tonicity agent, and water, has a pH of about 3.0 to about 3.6, and is substantially free of a conjugate base of the organic acid.