Pharmaceutical solid-state kinetic stability investigation by using moisture-modified Arrhenius equation and JMP...

Area of Science:

• Pharmaceutical Sciences
• Chemical Kinetics
• Drug Stability

Background:

• Investigational oncology drug MLNA requires robust stability assessment.
• Understanding degradation pathways is crucial for drug development and formulation.

Purpose of the Study:

• To quantitatively assess the solid-state stability of MLNA under accelerated stress conditions.
• To develop a predictive mathematical model for MLNA degradation kinetics.
• To evaluate the impact of temperature and humidity on MLNA stability.

Main Methods:

• Accelerated stress testing using temperature and humidity.
• Moisture-modified Arrhenius equation and JMP statistical software for modeling.
• Physical stability assessment via XRPD, DSC, TGA, and DVS.
• Chemical stability assessment via HPLC to identify and quantify degradation products.

Main Results:

• A hydrolysis product was identified as the major chemical degradant.
• A mathematical model (ln k=-11,991×(1/T)+0.0298×(%RH)+29.8823) showed a good fit (R²=0.94) to experimental data.
• Both temperature and humidity significantly impacted MLNA stability (p<0.05).
• A resource-efficient model using four conditions also provided a good fit.

Conclusions:

• The developed model accurately predicts MLNA degradation, supporting its use in setting specifications and storage conditions.
• Temperature and humidity are key factors influencing MLNA's chemical stability.
• The moisture-modified Arrhenius equation is a valid approach for modeling MLNA stability.