Simultaneous Water Sorption and Crystallization in ASDs 2: Modeling Long-Term Stabilities

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Physical stability of amorphous solid dispersions (ASDs) is critical for oral dosage forms.
• Investigating long-term ASD stability requires extensive, time-consuming experiments.

Purpose of the Study:

• To develop a thermodynamic and kinetic modeling framework to predict ASD crystallization kinetics.
• To understand the factors influencing ASD physical stability during storage below the glass transition temperature.

Main Methods:

• Simultaneous consideration of water-sorption and active pharmaceutical ingredient (API) crystallization kinetics.
• Development of a model predicting viscosity, supersaturation, and crystallinity over time.
• Validation against two-year crystallization experiments of ASDs containing nifedipine.

Main Results:

• The model accurately describes the interplay between water sorption and API crystallization.
• The framework successfully predicts long-term ASD stability based on short-term measurements.
• The approach explains diverse and unexpected crystallization behaviors observed in ASDs.

Conclusions:

• The developed modeling framework offers a powerful tool for predicting and understanding ASD physical stability.
• This approach minimizes the need for lengthy experimental investigations.
• It provides insights into the underlying mechanisms governing ASD crystallization.