A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Miscibility is key for amorphous solid dispersion (ASD) physical stability, preventing drug crystallization.
• Existing miscibility determination methods face theoretical and practical challenges.
• Developing robust methods for assessing ASD miscibility is critical for drug formulation.

Purpose of the Study:

• To introduce a novel, practical method for determining miscibility in ASDs.
• To establish a correlation between the overlap concentration (c*) and ASD physical stability.
• To provide a standardized procedure for wider adoption of this methodology.

Main Methods:

• Miscibility determination based on the overlap concentration (c*).
• Determination of c* from viscosity-composition diagrams.
• Evaluation of celecoxib and loratadine ASDs with polyvinylpyrrolidone (PVP).

Main Results:

• A strong correlation was found between determined c* values and ASD physical stability.
• The viscosity-based method successfully predicted miscibility for model drug-polymer systems.
• The overlap concentration (c*) serves as a reliable indicator of ASD physical stability.

Conclusions:

• The overlap concentration (c*) method offers a convenient and effective approach for miscibility determination in ASDs.
• This method can guide the development of stable, high-drug-loaded ASD formulations.
• The procedure is broadly applicable to thermally stable binary drug/polymer combinations.