Statistical analysis of long-term physical stability testing of amorphous solid dispersions

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing drug solubility and bioavailability.
• Understanding the factors influencing ASD physical stability is vital for effective drug formulation.
• Predicting ASD long-term stability remains a challenge due to complex underlying mechanisms.

Purpose of the Study:

• To investigate the impact of procedural and molecular-level factors on the long-term physical stability of amorphous solid dispersions (ASDs).
• To identify key variables influencing the crystallization rates of ASDs.
• To develop a statistically robust framework for predicting ASD stability.

Main Methods:

• Formulation of six model drugs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) into ASDs using solvent-based and mechanochemical methods.
• One-year stability studies under five different temperature and humidity conditions at maximum drug load.
• Application of logistic regression and survival analysis to quantitatively assess stability factors.

Main Results:

• Intermolecular hydrogen bonding was identified as a significant factor affecting ASD stability, with its influence varying based on drug-specific crystallization tendencies.
• Storage environment humidity was consistently found to significantly impact ASD stability across all statistical models.
• The study demonstrated a strong correlation between hydrogen bonding, humidity, and ASD crystallization rates.

Conclusions:

• Intermolecular hydrogen bonding and environmental humidity are critical predictors of amorphous solid dispersion stability.
• Statistical analysis of experimental data provides robust insights for optimizing ASD design and forecasting stability.
• This research offers a quantitative approach to enhance the development of stable amorphous solid dispersion dosage forms.