Oxygen-Dependent Accelerated Stability Modeling of Drug Products

Area of Science:

• Pharmaceutical Sciences
• Chemical Kinetics
• Materials Science

Background:

• Shelf-life determination is crucial for product stability.
• Traditional methods can be time-consuming.
• Environmental factors like temperature, humidity, and oxygen significantly impact degradation.

Purpose of the Study:

• To develop and validate a new formalism for accelerated shelf-life determination.
• To incorporate oxygen concentration as a key variable alongside temperature and humidity.
• To apply the formalism to real-world examples like liquid sesame oil and formulated tablets.

Main Methods:

• A modified Arrhenius equation incorporating an oxygen-sensitivity parameter (C) was developed.
• The isoconversion method was used for rate determinations focused on specification limits.
• The formalism was tested on sesame oil oxidation and chlorpromazine tablet degradation.

Main Results:

• The model accurately predicted degradation for both sesame oil and chlorpromazine tablets.
• Degradant formation in sesame oil showed independent temperature and oxygen effects (C ≈ 1).
• Chlorpromazine degradation exhibited nonlinear kinetics with independent environmental factor dependencies (C < 1), suggesting indirect oxidation via reactive oxygen species.

Conclusions:

• The proposed moisture and oxygen-modified Arrhenius equation provides an efficient and accurate method for shelf-life prediction.
• The findings highlight the independent roles of temperature, humidity, and oxygen in product degradation.
• The study validates the utility of the new formalism with real-time data for diverse products.