Epinephrine Stabilization via Inert Atmosphere Packaging

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Solution Overview

Problem

Current epinephrine products have limited stability at room temperature, requiring refrigerated storage and posing challenges for patient convenience and storage.

Innovation Solution

A method and container system for stabilizing epinephrine compositions using specific formulations and packaging techniques, including vacuum or gas overlay filling, secondary packaging with oxygen-absorbing means and indicators, and using containers like glass or plastic vials, to maintain stability at room temperature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If epinephrine is stored at room temperature, then patient convenience is improved, but product stability deteriorates

Engineering Contradiction:
Improvepatient convenienceVSAvoidproduct stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent applies inert atmosphere by filling the container headspace with nitrogen gas and incorporating oxygen-absorbing materials in the secondary packaging. This creates an oxygen-free environment that prevents oxidative degradation of epinephrine, enabling room temperature storage while maintaining product stability. The inert atmosphere directly addresses the technical contradiction by allowing convenient room temperature storage without compromising stability.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent uses oxygen-absorbing materials and antioxidants (sodium metabisulfite, ascorbic acid) as intermediary substances that actively remove or neutralize oxygen. These intermediaries protect epinephrine from oxidation by creating a protective chemical environment, thereby maintaining stability during room temperature storage and resolving the contradiction between convenience and stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If epinephrine is stored in refrigerated conditions, then product stability is improved, but patient convenience deteriorates

Engineering Contradiction:
Improveproduct stabilityVSAvoidpatient convenience
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

By implementing nitrogen flushing and oxygen-absorbing packaging, the patent eliminates the need for refrigerated storage. The inert atmosphere prevents degradation pathways that would otherwise require cold temperatures to slow down, thereby improving patient convenience while maintaining stability.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The patent changes the chemical environment parameters by adjusting pH to acidic conditions (pH 2-4) and incorporating specific stabilizers. These parameter changes fundamentally alter the stability profile of epinephrine, allowing it to remain stable at room temperature rather than requiring refrigeration, thus resolving the contradiction.

Inventive Principle:
Principle #35Parameter changes

3Object-generated harmful factors

If epinephrine is exposed to oxygen, then impurity formation increases, but the patent uses oxygen-absorbing means to prevent this

Engineering Contradiction:
Improveimpurity formationVSAvoidpackaging complexity
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The patent replaces oxygen with nitrogen in the container headspace and incorporates oxygen-absorbing materials in secondary packaging. This inert atmosphere prevents oxidative impurity formation by eliminating the reactive oxygen that causes degradation, directly addressing the harmful effect while the added packaging complexity is justified by the stability benefits.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

Oxygen-absorbing materials and antioxidants serve as intermediary substances that actively prevent oxygen from contacting the epinephrine solution. These intermediaries bind or neutralize oxygen, preventing impurity formation despite the increased packaging complexity, thereby resolving the contradiction between harmful effects and device complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 method and container system provide room temperature stability for epinephrine products, reducing impurity formation and maintaining effectiveness over six months at various storage conditions, as demonstrated by stability testing.

Implementation Method 1

secondary packaging with oxygen-absorbing means

Methodology Applied
Scientific EffectOxygen absorption: Absorption (physical)

Implementation Method 2

filling a container with the pharmaceutical composition under a vacuum or a gas overlay

Methodology Applied
Scientific EffectVacuum: Vacuum

Data Source

PatentUS11744811B2Methods of stabilizing epinephrine
Publication Date: 2023.09.05 HIKMA PHARMACEUTICALS USA INC

AI summary

The present invention is directed to methods of stabilizing a pharmaceutical composition comprising epinephrine containing the steps filling a container, capping the container, assembling the container and placing the assembled capped container (assembled device) in a secondary packaging system.