Theoretical Model for the Structural Relaxation Time in Coamorphous Drugs

Area of Science:

• Materials Science
• Physical Chemistry
• Pharmaceutical Science

Background:

• Amorphous drugs are crucial in pharmaceuticals but their glassy dynamics are complex.
• Understanding structural relaxation and glass transition is key for drug stability and formulation.

Purpose of the Study:

• To develop a simplified theoretical model for predicting structural relaxation time and glass transition in amorphous drugs.
• To validate the model's predictions against experimental data for pharmaceutical mixtures.

Main Methods:

• Modeling amorphous materials as collections of equal-sized hard spheres.
• Utilizing elastically collective nonlinear Langevin equation theory and Kramer's theory for theoretical calculations.
• Developing a thermal mapping technique to relate real materials to an effective hard-sphere fluid.

Main Results:

• Theoretical calculations of structural relaxation time over extended ranges.
• Quantitative agreement between numerical predictions and experimental results for binary pharmaceutical mixtures.
• Successful experimental validation using an ezetimibe-simvastatin-Kollidon VA64 mixture.

Conclusions:

• The proposed hard-sphere model provides a simple yet comprehensive framework for describing glassy dynamics in amorphous composites.
• This approach facilitates accurate prediction of temperature-dependent relaxation times, aiding in drug development.
• The method offers a valuable tool for comparing theoretical calculations with experimental findings in pharmaceutical science.