Oxidation-Resistant Infusion Bag for Moist Heat Sterilization
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Solution Overview
Problem
Existing methods for manufacturing stable, ready-to-use oxidation-sensitive drug formulations, such as acetaminophen, often require deoxygenation of the vehicle or use of a nitrogen blanket during manufacturing, which is not feasible in all scenarios, leading to degradation and impurity formation during terminal moist heat sterilization in flexible infusion bags.
Innovation Solution
A process involving moist heat sterilization of an oxidation-susceptible drug solution in a flexible infusion bag made of materials like cycloolefinic polymer or polypropylene, without deoxygenating the water or using a nitrogen blanket, at an air overpressure between 0.2 and 1.2 bar, while using overwraps to prevent oxygen, moisture, and light ingress, to maintain stability and reduce impurity formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If deoxygenation of the vehicle or nitrogen blanket is used during manufacturing, then oxidation stability of the formulation is improved, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent removes the harmful factor (oxygen) from the system by conducting moist heat sterilization in an oxygen-free environment using sealed flexible containers, eliminating the need for deoxygenation equipment or nitrogen blankets while maintaining oxidation stability
Solution Approach 2:
The patent creates an inert environment by sealing the drug solution in flexible infusion bags that exclude oxygen during moist heat sterilization, achieving oxidation protection without requiring active inert gas systems or complex deoxygenation apparatus
2Ease of manufacture
If terminal moist heat sterilization is performed in flexible infusion bags without deoxygenation, then manufacturing simplicity is improved, but oxidation degradation and impurity formation increase
Solution Approach 1:
The patent creates an oxygen-excluding environment by sealing the flexible infusion bag before sterilization, providing a passive inert atmosphere that prevents oxidation and impurity formation during heat sterilization without requiring active gas management systems
Solution Approach 2:
The patent performs preliminary sealing of the flexible infusion bag to exclude oxygen before the sterilization process begins, preventing oxidation from occurring during the subsequent heat treatment rather than attempting to remove oxygen after sterilization
3Stability of the object's composition
If traditional glass bottle methods with nitrogen bubbling are used, then oxidation protection is improved, but manufacturing cost and complexity increase
Solution Approach 1:
The patent uses disposable flexible infusion bags that are sealed and sterilized as single-use containers, eliminating the need for expensive glass bottles and complex nitrogen handling systems while maintaining oxidation protection throughout the product lifecycle
Solution Approach 2:
The patent achieves oxidation protection by creating a sealed oxygen-excluding environment in flexible bags during sterilization, replacing the need for nitrogen bubbling apparatus and continuous inert gas maintenance required by traditional glass bottle methods
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
This approach results in a stable, ready-to-use parenteral drug product with less than 0.1% degradation of the oxidation-susceptible API, reducing impurity levels and maintaining product integrity without the need for inert gas handling, and demonstrating improved stability compared to traditional glass bottle methods.
Implementation Method 1
sterilizing a drug solution comprising an oxidation-susceptible API dissolved in water, said drug solution being contained in a moist heat sterilizable container... wherein said plastic material is a cycloolefinic polymer, a polypropylene polymer, a polyvinyl chloride polymer
Implementation Method 2
sterilizing a drug solution comprising an oxidation-susceptible API dissolved in water, said drug solution being contained in a moist heat sterilizable container, said moist heat sterilization being performed at an air overpressure between about 0.2 bar to about 1.2 bar
Data Source
AI summary
A process for minimizing formation of a highest degradation product during moist heat sterilization of a drug solution of an oxidation susceptible active pharmaceutical ingredient (API) is provided, wherein the water is not deoxygenated and a nitrogen blanket is not used during formulation, or the formulation is stored in ambient conditions in the polymer bag and autoclaved. The highest degradation product in the parenteral drug product is less than 0.1% by weight of a labeled amount of the oxidation susceptible API in the parenteral drug product.