Sufentanil Solid Dosage Forms with Oxygen Scavenger Packaging
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Solution Overview
Problem
Oxidative degradation of sufentanil in low dose solid dosage forms prepared using aqueous and/or organic solvents leads to stability issues during storage, particularly at elevated temperatures and varying humidity conditions, necessitating effective measures to minimize or eliminate oxidative degradation products.
Innovation Solution
Incorporating an oxygen scavenger in the primary packaging of sufentanil drug dosage forms, which can be housed in a substantially oxygen impermeable container, such as a foil pouch, to reduce or eliminate oxidative degradation products, thereby maintaining the integrity of the active drug over extended storage periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If sufentanil is formulated in low dose solid dosage forms using aqueous and/or organic solvents, then the drug can be delivered in small volumes, but oxidative degradation occurs during storage particularly at elevated temperatures and varying humidity conditions
Solution Approach 1:
An oxygen scavenger is introduced as an intermediary substance within the packaging system. The scavenger chemically reacts with oxygen molecules, removing them from the environment surrounding the sufentanil dosage form. This mediator prevents direct contact between oxygen and the drug, thereby eliminating oxidative degradation while maintaining the small volume solid dosage form structure
Solution Approach 2:
The packaging system creates an inert atmosphere by incorporating oxygen scavenging materials that consume oxygen and generate an oxygen-depleted environment. This inert atmosphere protects the sufentanil from oxidation during storage under various temperature and humidity conditions, resolving the contradiction between small volume formulation and drug stability
2Stability of the object's composition
If preservatives and antioxidants are employed in the pharmaceutical formulation, then oxidative degradation is addressed, but the formulation complexity increases
Solution Approach 1:
The oxidation problem is extracted from the formulation itself and relocated to the packaging system. Instead of incorporating preservatives and antioxidants into the drug formulation, the solution places oxygen scavengers in the packaging, separating the stability function from the pharmaceutical composition and thereby reducing formulation complexity while maintaining stability
Solution Approach 2:
The oxygen scavenger acts as an intermediary barrier between oxygen and the sufentanil, eliminating the need for chemical additives within the formulation. This mediator approach maintains formulation simplicity while achieving the desired stability outcome
3Stability of the object's composition
If oxygen scavengers are incorporated in the packaging system, then oxidative degradation products are reduced or eliminated, but the packaging complexity increases
Solution Approach 1:
The packaging system is designed with multi-functionality, where the oxygen scavenger serves multiple purposes: it protects against oxidation, extends shelf life, and maintains drug efficacy under various storage conditions. This universal approach justifies the increased packaging complexity by delivering comprehensive protection without requiring multiple separate systems
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 use of oxygen scavengers in the packaging significantly reduces or eliminates sufentanil oxidative degradation products, ensuring the stability and efficacy of the drug dosage forms during storage for at least 6 months under different environmental conditions, including 5°C, 25°C, and 40°C, with relative humidities of 60% and 75%.
Implementation Method 1
Oxygen scavengers or displacement of oxygen with an inert gas in the headspace of a finished product has been used to reduce the generation of oxidative degradation products
Data Source
AI summary
Compositions and methods effective to minimize or eliminate the presence of oxidative degradation products in solid dosage forms comprising sufentanil are provided.