Plastic Norepinephrine Formulation With Low Surface Exposure Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Norepinephrine formulations are prone to degradation, particularly due to oxidation and the formation of impurities like 1,2,3,4-tetrahydroisoquinoline-4,6,7-triol, especially when stored in plastic containers.
Innovation Solution
The formulation is contained in a plastic container with a controlled surface area to volume ratio of less than 3.0 cm−1, minimizing the formation of 1,2,3,4-tetrahydroisoquinoline-4,6,7-triol impurity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If norepinephrine is stored in plastic containers, then convenience of storage and transport is improved, but degradation into impurities like 1,2,3,4-tetrahydroisoquinoline-4,6,7-triol occurs
Solution Approach 1:
The patent changes the geometric parameters of the container by controlling the surface area to volume ratio to be less than 3.0 cm⁻1. This parameter modification reduces the relative surface area exposed to the norepinephrine solution, thereby minimizing oxidation and degradation reactions while maintaining the convenience of plastic container storage.
2Stability of the object's composition
If the surface area of the plastic container is reduced, then impurity formation is minimized, but the container size is constrained
Solution Approach 1:
The patent establishes a specific parameter range for the surface area to volume ratio (less than 3.0 cm⁻1) that balances impurity minimization with practical container sizing. This allows for extended storage periods while maintaining acceptable container dimensions for clinical use.
3Stability of the object's composition
If norepinephrine is stored at higher concentrations, then storage stability is improved, but the formulation becomes more prone to degradation
Solution Approach 1:
The patent changes the concentration parameter of the norepinephrine formulation to low concentrations (0.01-0.1 mg/ml), which counterintuitively improves stability by reducing the driving force for oxidation reactions, while the container geometry parameter (surface area to volume ratio < 3.0 cm⁻1) further suppresses degradation pathways.
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 solution enhances the stability of norepinephrine formulations, allowing them to be stored for extended periods with minimal impurity formation, maintaining effectiveness for administration.
Implementation Method 1
Norepinephrine is sensitive to oxidation and will normally degrade into several oxidation-related impurities. Norepinephrine is therefore often protected from oxygen by degassing the solutions used for producing the norepinephrine formulation and/or including an antioxidant in the final formulation.
Data Source
AI summary
Described herein are ready-to-administer products comprising liquid norepinephrine formulations contained in a flexible plastic container