Intranasal Vial Headspace Oxygen Reduction for Ketorolac Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Ketorolac solutions for nasal administration face stability issues due to high oxygen content in the headspace of vials, leading to degradation and reduced shelf life, necessitating refrigeration, which increases handling and storage costs.
Innovation Solution
A vial design with a headspace containing no more than 10% v/v oxygen, achieved through the use of a nasal spray system and an improved oxygen reduction device that purges air with inert gases like nitrogen or argon, ensuring long-term stability at room temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the vial headspace contains normal air (21% oxygen), then the vial structure is simple and manufacturing is easy, but the ketorolac solution degrades rapidly and shelf life is reduced
Solution Approach 1:
The patent applies the inert atmosphere principle by replacing oxygen-containing air with nitrogen gas in the vial headspace. This prevents oxidation of the ketorolac solution, thereby extending shelf life to 24 months without refrigeration. The nitrogen atmosphere is achieved through purging the headspace with nitrogen gas during or after filling, creating an oxygen-free environment that maintains solution stability.
2Reliability
If refrigeration is used to maintain ketorolac solution stability, then degradation is reduced, but handling and storage costs increase
Solution Approach 1:
By creating an inert nitrogen atmosphere in the vial headspace, the patent eliminates the need for refrigeration to prevent degradation. The nitrogen barrier stops oxidation reactions, allowing the solution to remain stable at room temperature for 24 months, thereby eliminating continuous energy expenditure for cooling and reducing storage infrastructure requirements.
Solution Approach 2:
The patent applies preliminary action by establishing the nitrogen atmosphere during the filling process itself. The headspace is purged with nitrogen gas either before or during solution filling, creating a protective atmosphere in advance. This pre-established inert environment prevents degradation from the outset, eliminating the need for subsequent refrigeration.
3Duration of action of stationary object
If the headspace oxygen content is reduced to no more than 10% v/v, then shelf life is extended without refrigeration, but the manufacturing process becomes more complex
Solution Approach 1:
The patent implements headspace oxygen reduction by introducing nitrogen gas during the filling process. The nitrogen purges the headspace, displacing oxygen to achieve less than 10% v/v oxygen content. This is integrated into the manufacturing process, where nitrogen is introduced either before filling, during filling, or after filling, followed by sealing to maintain the reduced oxygen environment.
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 reduced oxygen content in the vial headspace extends the shelf life of ketorolac solutions without refrigeration, maintaining stability for two years or more, reducing degradation products and associated safety concerns.
Implementation Method 1
achieved through the use of a nasal spray system and an improved oxygen reduction device that purges air with inert gases like nitrogen or argon
Data Source
AI summary
Disclosed herein are devices and processes for preparing a vial for an intranasal administration of a medicament where the vial comprises reduced oxygen content.