Is a distinctive single Tg a reliable indicator for the homogeneity of amorphous solid dispersion?

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) enhance drug solubility and bioavailability.
• Homogeneous mixing in ASDs is crucial for drug stability and preventing crystallization.
• A single glass transition temperature (T(g)) is traditionally used to assess mixing uniformity.

Purpose of the Study:

• To investigate the reliability of a single T(g) as an indicator of homogeneity and stability in ASDs.
• To evaluate the physical stability of ASDs prepared under different processing conditions.
• To explore advanced characterization techniques for assessing ASD homogeneity.

Main Methods:

• Preparation of amorphous solid dispersions of BMS-A (drug) and PVP-VA (polymer) using twin-screw hot-melt extrusion.
• Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) for crystallinity assessment.
• Raman mapping to analyze drug distribution and concentration gradients within the ASDs.

Main Results:

• Both ASD batches exhibited a single, distinct T(g), suggesting homogeneous mixing via Fox equation.
• DSC and PXRD confirmed the absence of drug crystallinity in both batches.
• Despite similar T(g) and lack of crystallinity, the two batches showed different physical stabilities.
• Raman mapping revealed wider drug concentration distribution in the less stable ASD batch.

Conclusions:

• A single T(g) alone is not always a sufficient indicator of homogeneity and optimal stability in ASDs.
• Drug distribution heterogeneity, not detectable by conventional methods, can impact ASD physical stability.
• Advanced techniques like Raman mapping are essential for comprehensive ASD characterization and stability prediction.