Assessing Physical Stability of Colloidal Dispersions Using a Turbiscan Optical Analyzer

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Physical stability of amorphous solid dispersions (ASDs) is critical for drug formulation.
• Highly concentrated droplets of poorly water-soluble drugs in ASDs present significant stability challenges.
• Understanding droplet coalescence is essential for developing stable ASDs.

Purpose of the Study:

• To investigate the physical stability of colloidal dispersions containing ritonavir as a model drug for ASD development.
• To evaluate the utility of the Turbiscan analyzer for assessing ASD colloidal stability.
• To determine the influence of drug concentration, temperature, and polymer additives on droplet coalescence.

Main Methods:

• Utilized the Turbiscan analyzer, based on multiple light scattering, to monitor colloidal dispersions.
• Employed a novel experimental procedure to determine the glass transition temperature of water-saturated amorphous ritonavir.
• Assessed the impact of varying drug concentrations, temperatures, and polymer additives on droplet stability.

Main Results:

• Confirmed droplet coalescence as the primary mechanism of physical instability in ritonavir-rich droplets.
• Demonstrated that higher drug concentrations significantly accelerate the coalescence process.
• Showcased varying stabilization effectiveness of polymers based on hydrophobicity and drug-polymer interactions.

Conclusions:

• The Turbiscan analyzer serves as a rapid, high-throughput screening tool for evaluating excipients in ASD development.
• Understanding coalescence kinetics and the role of polymer additives is crucial for enhancing ASD physical stability.
• This approach supports the rational design of stable amorphous solid dispersion formulations.