Ephedrine Formulation pH Stability and Ready-to-Administer Design
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Solution Overview
Problem
Existing injectable ephedrine formulations are not stable and require dilution before administration, leading to pH instability and potential degradation during storage.
Innovation Solution
A stable, ready-to-administer formulation comprising ephedrine sulfate, a tonicity agent, and a citrate buffer, with a pH of 5.2 to 5.4, which maintains a pH drift of less than 0.3 units after storage for at least 6 months at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If ephedrine is formulated as a ready-to-administer injectable solution, then convenience of administration is improved, but pH stability deteriorates during storage
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range to 4.5-5.5 and controlling buffer concentration (1-10 mM citrate buffer) to achieve both readiness for administration and long-term pH stability. This resolves the contradiction by finding the optimal parameter window where the formulation remains stable during storage while requiring no dilution before use.
2Ease of operation
If ephedrine formulation is stored at room temperature for long durations, then accessibility and ease of use are improved, but pH drift and degradation increase
Solution Approach 1:
The formulation incorporates citrate buffer and tonicity agents during manufacturing to pre-establish pH stability before storage. This preliminary action ensures that when the product is stored at room temperature for extended periods, the pH remains stable within 0.3 units drift, maintaining reliability without requiring refrigeration or special storage conditions.
3Quantity of substance
If ephedrine sulfate is used at higher concentrations, then therapeutic effectiveness is improved, but impurity formation increases during storage
Solution Approach 1:
The citrate buffer acts as an intermediary that stabilizes the pH environment, preventing ephedrine degradation and impurity formation even at therapeutic concentrations of 5 mg/mL. The buffer mediates between the ephedrine sulfate and the aqueous environment, maintaining pH within the stable range and minimizing harmful degradation products during long-term storage.
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 potency of ephedrine, with minimal impurity formation and pH stability, allowing for direct administration without prior dilution.
Implementation Method 1
a citrate buffer, with a pH of 5.2 to 5.4, which maintains a pH drift of less than 0.3 units after storage for at least 6 months
Implementation Method 2
a tonicity agent
Data Source
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AI summary
The present invention provides a formulation that includes a therapeutically effective amount of ephedrine or a pharmaceutically acceptable salt thereof, and a method for preparing the formulation. In some embodiments, the formulation includes a tonicity agent, a citrate buffer, water, and has a pH of about 5.2-5.4. The formulation of the invention is stable and ready-to-administer.